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1. Treatment with bulevirtide in HIV-infected patients with chronic hepatitis D: ANRS HD EP01 BuleDelta and compassionate cohort

Author: Victor de Lédinghen, Claire Fougerou-Leurent, Estelle Le Pabic, Stanislas Pol, Dulce Alfaiate, Karine Lacombe, Marie-Noëlle Hilleret, Caroline Lascoux-Combe, Anne Minello, Eric Billaud, Isabelle Rosa, Anne Gervais, Vlad Ratziu, Nathalie Ganne, Georges-Philippe Pageaux, Vincent Leroy, Véronique Loustaud-Ratti, Philippe Mathurin, Julie Chas, Caroline Jezequel, Sophie Métivier, Jérôme Dumortier, Jean-Pierre Arpurt, Tarik Asselah, Bruno Roche, Antonia Le Gruyer, Marc-Antoine Valantin, Caroline Scholtès, Emmanuel Gordien, Christelle Tual, Amel Kortebi, Fatoumata Coulibaly, Eric Rosenthal, Miroslava Subic-Levrero, Dominique Roulot, Fabien Zoulim, François Raffi, Laurent Alric, Patrick Miailhes, Albert Tran, Christiane Stern, Xavier Causse, Simona Tripon, Ghassan Riachi, Olivier Chazouillères, Armando Abergel, Louis d’Alteroche, Jérôme Gournay, Garance Lagadic, Patrizia Carrieri, Ségolène Brichler, Martin Siguier, Jessica Krause, Juliette Foucher, Souad Ben Ali, Magdalena Meszaros, Anne Varaut, and Valérie Canva
Subjects: Cirrhosis, HDV, HBV, Pegylated interferon, Hepatitis D, HDV RNA, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: In France, bulevirtide (BLV) became available in September 2019 through an early access program to treat patients with HDV. The aim of this analysis was to evaluate the efficacy and safety of BLV in patients with HIV and HDV coinfection. Methods: Patients received BLV 2 mg ± pegylated interferon-α (pegIFNα) according to the physician’s decision. The primary endpoint (per-protocol analysis) was the virological response rate at Week 48, defined as the proportion of patients with undetectable serum HDV RNA or a HDV RNA decline >2 log10 IU/ml from baseline. Results: The characteristics of the 38 patients were as follows: 28 male, mean age 47.7 years, and mean baseline HDV RNA viral load 5.7 ± 1.2 log10 IU/ml. Median HIV viral load and mean CD4 count were 32 (30–65) copies/ml and 566 ± 307/mm3, respectively. Eight patients stopped treatment before Week 48. At Week 48, 10 of 19 patients (52.6%) in the 2 mg BLV group and five of seven patients (71.4%) in the 2 mg BLV + pegIFNɑ group had reached virological response (no HDV RNA available in four patients). At Week 48, seven of 19 patients in the 2 mg BLV group and three of six patients in the 2 mg BLV + pegIFNɑ group had a combined response (virological response and normal alanine aminotransferase level). Conclusions: Adults living with HIV coinfected with HDV can be treated by BLV with a virological response in more than 50% of patients. The combination of BLV and pegIFNɑ showed a strong virological response. Impact and implications: Bulevirtide is the only EMA-approved drug for HDV treatment, and we showed that it can be used in adults living with HIV, with an overall good tolerability. Bulevirtide induces a virological response in more than 50% of patients, suggesting that bulevirtide should be considered as a first-line therapy in this specific population. Bulevirtide in combination with pegIFNα could be used in patients without pegIFNα contraindication. No specific drug–drug interaction is reported. Bulevirtide is the only EMA-approved drug for HDV treatment, and we showed that it can be used in adults living with HIV, with an overall good tolerability. Bulevirtide induces a virological response in more than 50% of patients, suggesting that bulevirtide should be considered as a first-line therapy in this specific population. Bulevirtide in combination with pegIFNα could be used in patients without pegIFNα contraindication. No specific drug–drug interaction is reported. Bulevirtide is the only EMA-approved drug for HDV treatment, and we showed that it can be used in adults living with HIV, with an overall good tolerability. Bulevirtide induces a virological response in more than 50% of patients, suggesting that bulevirtide should be considered as a first-line therapy in this specific population. Bulevirtide in combination with pegIFNα could be used in patients without pegIFNα contraindication. No specific drug–drug interaction is reported.
Published: 2024
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2. Protective potential of the gallbladder in primary sclerosing cholangitis

Author: Nora Cazzagon, Ester Gonzalez-Sanchez, Haquima El-Mourabit, Dominique Wendum, Dominique Rainteau, Lydie Humbert, Christophe Corpechot, Olivier Chazouillères, Lionel Arrivé, Chantal Housset, and Sara Lemoinne
Subjects: Abcb4 knockout mice, Bile acids, Cholecystectomy, Gallbladder volume, Magnetic resonance imaging, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: Gallbladder enlargement is common in patients with primary sclerosing cholangitis (PSC). The gallbladder may confer hepatoprotection against bile acid overload, through the sequestration and cholecystohepatic shunt of bile acids. The aim of this study was to assess the potential impact of the gallbladder on disease features and bile acid homeostasis in PSC. Methods: Patients with PSC from a single tertiary center who underwent liver MRI with three-dimensional cholangiography and concomitant analyses of serum bile acids were included. Gallbladder volume was measured by MRI and a cut-off of 50 ml was used to define gallbladder enlargement. Bile acid profiles and PSC severity, as assessed by blood tests and MRI features, were compared among patients according to gallbladder size (enlarged vs. normal-sized) or presence (removed vs. conserved). The impact of cholecystectomy was also assessed in the Abcb4 knockout mouse model of PSC. Results: Sixty-one patients with PSC, all treated with ursodeoxycholic acid (UDCA), were included. The gallbladder was enlarged in 30 patients, whereas 11 patients had been previously cholecystectomized. Patients with enlarged gallbladders had significantly lower alkaline phosphatase, a lower tauro-vs. glycoconjugate ratio and a higher UDCA vs. total bile acid ratio compared to those with normal-sized gallbladders. In addition, gallbladder volume negatively correlated with the hydrophobicity index of bile acids. Cholecystectomized patients displayed significantly higher aspartate aminotransferase and more severe bile duct strictures and dilatations compared to those with conserved gallbladder. In the Abcb4 knockout mice, cholecystectomy caused an increase in hepatic bile acid content and in circulating secondary bile acids, and an aggravation in cholangitis, inflammation and liver fibrosis. Conclusion: Altogether, our findings indicate that the gallbladder fulfills protective functions in PSC. Impact and implications: In patients with primary sclerosing cholangitis (PSC), gallbladder status impacts on bile acid homeostasis and disease features. We found evidence of lessened bile acid toxicity in patients with PSC and enlarged gallbladders and of increased disease severity in those who were previously cholecystectomized. In the Abcb4 knockout mouse model of PSC, cholecystectomy causes an aggravation of cholangitis and liver fibrosis. Overall, our results suggest that the gallbladder plays a protective role in PSC.
Published: 2023
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3. Quantitative magnetic resonance cholangiopancreatography metrics are associated with disease severity and outcomes in people with primary sclerosing cholangitis

Author: Nora Cazzagon, Sanaâ El Mouhadi, Quentin Vanderbecq, Carlos Ferreira, Sarah Finnegan, Sara Lemoinne, Christophe Corpechot, Olivier Chazouillères, and Lionel Arrivé
Subjects: MRCP+, Prognosis, Magnetic resonance imaging, Liver stiffness, Cholestasis, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: People with primary sclerosing cholangitis (PSC) have a variable and often progressive disease course that is associated with biliary and parenchymal changes. These changes are typically assessed by magnetic resonance imaging (MRI), including qualitative assessment of magnetic resonance cholangiopancreatography (MRCP). Our aim was to study the association of novel objective quantitative MRCP metrics with prognostic scores and patient outcomes. Methods: We performed a retrospective study including 77 individuals with large-duct PSC with baseline MRCP images, which were postprocessed to obtain quantitative measures of bile ducts using MRCP+™. The participants’ ANALI scores, liver stiffness by vibration-controlled transient elastography, and biochemical indices were collected at baseline. Adverse outcome-free survival was measured as the absence of decompensated cirrhosis, liver transplantation (LT), or liver-related death over a 12-year period. The prognostic value of MRCP+-derived metrics was assessed by Cox regression modelling. Results: During a total of 386 patients-years, 16 cases of decompensation, 2 LTs, and 5 liver-related deaths were recorded. At baseline, around 50% of the patients were classified as being at risk of developing disease complications. MRCP+ metrics, particularly those describing the severity of bile duct dilatations, were correlated with all prognostic factors. Univariate analysis showed that MRCP+ metrics representing duct diameter, dilatations, and the percentage of ducts with strictures and/or dilatations were associated with survival. In a multivariable-adjusted analysis, the median duct diameter was significantly associated with survival (hazard ratio 10.9, 95% CI 1.3–90.3). Conclusions: MRCP+ metrics in people with PSC correlate with biochemical, elastographic, and radiological prognostic scores and are predictive of adverse outcome-free survival. Lay summary: In this study, we assessed in people with primary sclerosing cholangitis (PSC) the association of novel objective quantitative MRCP metrics automatically provided by a software tool (MRCP+) with prognostic scores and patient outcomes. We observed that MRCP+ metrics in people with PSC correlate with biochemical, elastographic, and radiological prognostic scores and are predictive of adverse outcome-free survival.
Published: 2022
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4. New treatments/targets for primary biliary cholangitis

Author: Christophe Corpechot, Raoul Poupon, and Olivier Chazouillères
Subjects: Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Summary: Primary biliary cholangitis (PBC) is an autoimmune, cholestatic, chronic liver disease that ultimately progresses towards cirrhosis and liver failure if untreated. While ursodeoxycholic acid has been established as standard of care for PBC in the last few decades, significant advances in second-line treatment options have recently been made and new therapeutic developments are currently under evaluation. The purpose of this article is to provide the clinician with an overview of the current treatment options and future opportunities for patients with PBC. Keywords: PBC, ursodeoxycholic acid, obeticholic acid, fibrates, FXR, PPAR, cholestasis, inflammation, liver disease
Published: 2019
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5. Impact of cirrhosis aetiology on incidence and prognosis of hepatocellular carcinoma diagnosed during surveillance

Author: Nathalie Ganne-Carrié, Pierre Nahon, Cendrine Chaffaut, Gisèle N’Kontchou, Richard Layese, Etienne Audureau, Sylvie Chevret, Isabelle Archambeaud, Louis d’Alteroche, Frédéric Oberti, Dominique Roulot, Christophe Moreno, Alexandre Louvet, Thông Dao, Romain Moirand, Odile Goria, Eric Nguyen-Khac, Nicolas Carbonell, Jean-Charles Duclos-Vallée, Stanislas Pol, Victor de Ledinghen, Violaine Ozenne, Jean Henrion, Jean-Marie Péron, Albert Tran, Gabriel Perlemuter, Xavier Amiot, Jean-Pierre Zarski, Tarik Asselah, Dominique Guyader, Hélène Fontaine, Georges-Philippe Pageaux, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Jean-Pierre Bronowicki, Thomas Decaens, Ghassan Riachi, Paul Calès, Laurent Alric, Marc Bourlière, Philippe Mathurin, Sebastien Dharancy, Jean-Frédéric Blanc, Armand Abergel, Olivier Chazouillères, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, Claire Wartelle, Dominique Thabut, Christophe Pilette, Christine Silvain, Christos Christidis, Brigitte Bernard-Chabert, Sophie Hillaire, and Vincent Di Martino
Subjects: alcoholic liver disease, cirrhosis, primary liver cancer, competing risk analysis, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: In this study we aimed to analyse the impact of the aetiology of cirrhosis on the incidence, characteristics and prognosis of hepatocellular carcinoma (HCC) diagnosed during a surveillance program. Methods: Individual data from a randomized trial and 2 prospective cohorts of patients with compensated histologically proven cirrhosis recruited between 2000 and 2016 were pooled. The influence of cirrhosis aetiology on survival after HCC detection was assessed using multivariable regression models. Results: Among 3,533 patients (1,926 virus [VIR], 1,167 alcohol [ALC], 440 combined [MIX]), 431 were diagnosed with HCC after a median follow-up of 57.1 months. The 5-year HCC incidence was lowest in ALC (VIR 12.6%, ALC 9.1%, MIX 14.3%, p = 0.04). At the time of diagnosis, tumour burden and Child-Pugh score were comparable across aetiology groups, but early BCLC stages (0/A) were significantly less frequent in ALC (VIR 80%, ALC 37%, MIX 72%) as a result of worse ECOG performance status. However, similar access to first-line curative HCC treatment was reported across aetiology groups (p = 0.68). Median survival after HCC diagnosis was significantly reduced in ALC (VIR 39, ALC 21, MIX 34 months, p = 0.02). However, when adjusting for tumour size, ECOG and Child-Pugh score, the aetiology of the underlying cirrhosis no longer had a significant impact. Conclusion: Compared to patients with virus-related cirrhosis, patients with alcohol-related compensated cirrhosis enrolled in a surveillance program have: i) the lowest 5-year HCC incidence; ii) worse overall prognosis, mostly driven by a poor general condition, despite similar access to first-line curative treatment. Lay summary: It has been suggested that early detection of hepatocellular carcinoma (HCC) may be futile in patients with alcohol-related cirrhosis. By comparing outcomes in more than 3,000 patients with compensated cirrhosis included in surveillance programs, this study suggests that HCC surveillance enables early diagnosis in most patients with alcohol-related cirrhosis despite a higher competing risk of death in these patients. We also report similar access to first-line curative HCC treatment in these patients compared to those with viral cirrhosis, despite higher rates of comorbidities and impaired liver function. Following HCC detection, the later parameters were major drivers of death irrespective of the cause of cirrhosis. Registration: CHC2000 (NCT00190385) and CIRRAL (NCT01213927) cohorts were registered at ClinicalTrials.gov and the full protocols are available at the following links (https://clinicaltrials.gov/ct2/show/NCT00190385) and https://clinicaltrials.gov/ct2/show/NCT01213927, respectively). The full CirVir protocol is available via the ANRS Web site (http://anrs.fr).
Published: 2021
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6. Low-phospholipid-associated cholelithiasis syndrome: Prevalence, clinical features, and comorbidities

Author: Catherine Dong, Bertrand Condat, Magalie Picon-Coste, Yves Chrétien, Pascal Potier, Béatrice Noblinski, Lionel Arrivé, Marie-Pierre Hauuy, Véronique Barbu, Anware Maftouh, Farid Gaouar, Karima Ben Belkacem, Chantal Housset, Raoul Poupon, David Zanditenas, Olivier Chazouillères, and Christophe Corpechot
Subjects: LPAC, ABCB4, Cholestasis, Pregnancy, Metabolic syndrome, Cancer, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: Low-phospholipid-associated cholelithiasis (LPAC) syndrome, a rare genetic form of intrahepatic cholelithiasis in adults, is still poorly understood. We report the results of the largest-ever case-control study of patients with LPAC syndrome aiming to assess the prevalence, clinical features, and comorbidities of the disease. Methods: We included all LPAC cases diagnosed between 2001 and 2016 in 11 French centres. Controls consisted of all patients who underwent a cholecystectomy for common gallstone disease in a single non-academic centre over 1 year. A logistic regression analysis was used to identify the clinical features associated with LPAC syndrome across several patient strata with increasing levels of diagnostic confidence. The ratio between the incident cases of LPAC syndrome and the total number of cholecystectomies for gallstones was used to assess the relative prevalence of the disease. Results: In this study, 308 cases and 206 controls were included. LPAC syndrome accounted for 0.5–1.9% of all patients admitted with symptomatic gallstone disease. Age at first symptoms
Published: 2021
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7. Long‐term outcome of liver transplantation for autoimmune hepatitis: A French nationwide study over 30 years

Author: Yasmina Chouik, Olivier Chazouillères, Claire Francoz, Eleonora De Martin, Olivier Guillaud, Armand Abergel, Mario Altieri, Louise Barbier, Camille Besch, Filomena Conti, Christophe Corpechot, Sébastien Dharancy, François Durand, Christophe Duvoux, Jean Gugenheim, Jean Hardwigsen, Marie‐Noëlle Hilleret, Pauline Houssel‐Debry, Nassim Kamar, Delphine Maucort‐Boulch, Anne Minello, Martine Neau‐Cransac, Georges‐Philippe Pageaux, Sylvie Radenne, Olivier Roux, Faouzi Saliba, Olivier Serée, Didier Samuel, Claire Vanlemmens, Marie‐Lorraine Woehl‐Jaegle, Vincent Leroy, Jean‐Charles Duclos‐Vallée, and Jérôme Dumortier
Subjects: Hepatology
Published: 2023
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8. Integrating genetic variants into clinical models for hepatocellular carcinoma risk stratification in cirrhosis

Author: Pierre Nahon, Jessica Bamba-Funck, Richard Layese, Eric Trépo, Jessica Zucman-Rossi, Carole Cagnot, Nathalie Ganne-Carrié, Cendrine Chaffaut, Erwan Guyot, Marianne Ziol, Angela Sutton, Etienne Audureau, Tarik Asselah, Dominique Guyader, Stanislas Pol, Hélène Fontaine, Georges-Philippe Pageaux, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Dominique Roulot, Albert Tran, Jean-Pierre Bronowicki, Thomas Decaensi, Ghassan Riachi, Paul Calès, Jean-Marie Péron, Laurent Alric, Marc Bourlière, Philippe Mathurin, Sebastien Dharancy, Jean-Frédéric Blanc, Armand Abergel, Olivier Chazouillères, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, null Louis d’Alteroche, Claire Wartelle, Thông Dao, Dominique Thabut, Christophe Pilette, Christine Silvain, Christos Christidis, Eric Nguyen-Khac, Brigitte Bernard-Chabert, Sophie Hillaire, Vincent Di Martino, Isabelle Archambeaud, Louis d’Alteroche, Frédéric Oberti, Christophe Moreno, Alexandre Louvet, Romain Moirand, Odile Goria, Nicolas Carbonell, Jean-Charles Duclos-Vallée, Victor de Ledinghen, Violaine Ozenne, Jean Henrion, Gabriel Perlemuter, Xavier Amiot, Jean-Pierre Zarski, and Sylvie Chevret
Subjects: Hepatology
Abstract: This study aimed to evaluate the ability of single nucleotide polymorphisms (SNPs) to refine hepatocellular carcinoma (HCC) risk stratification.Six SNPs in PNPLA3, TM6SF2, HSD17B13, APOE, and MBOAT7 affecting lipid turnover and one variant involved in the Wnt-β-catenin pathway (WNT3A-WNT9A rs708113) were assessed in patients with alcohol-related and/or HCV-cured cirrhosis included in HCC surveillance programs (prospective CirVir and CIRRAL cohorts). Their prognostic value for HCC occurrence was assessed using Fine-Gray models combined into a 7-SNP genetic risk score (GRS). Prediction ability of two clinical scores (a routine nongenetic model determined by multivariate analysis and the external aMAP score) without then with the addition of the GRS was evaluated by C-indices. The standardized net benefit was derived from decision curves.Among 1145 patients, 86 (7.5%) developed HCC after 43.7 months. PNPLA3 and WNT3A-WNT9A variants were independently associated with HCC occurrence. The GRS stratified the population into 3 groups with progressively increased 5-yr HCC incidence [Group 1 (n=627, 5.4%), Group 2 (n=276, 10.7%), and Group 3 (n=242, 15.3%); P0.001]. The multivariate model identified age, male sex, diabetes, platelet count, GGT levels, albuminemia and the GRS as independent risk factors. The clinical model performance for 5-yr HCC prediction was similar to that of the aMAP score (C-Index 0.769). The addition of the GRS to both scores modestly improved their performance (C-Index 0.786 and 0.783, respectively). This finding was confirmed by decision curve analyses showing only fair clinical net benefit.Patients with cirrhosis can be stratified into HCC risk classes by variants affecting lipid turnover and Wnt-β-catenin pathway. The incorporation of this genetic information modestly improves the performance of clinical scores.The identification of patients at higher probability of developing liver cancer is pivotal to improve the performance of surveillance. Risk assessment can be achieved by combining several clinical and biological parameters used in routine practice. The addition of patients' genetic characteristics can modestly improve this prediction and will ultimately pave the way for precision medicine in patients eligible for HCC surveillance, allowing physicians to trigger personalized screening strategies.
Published: 2023
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9. Liver transplantation for autoimmune hepatitis: Pre‐transplant does not predict the early post‐transplant outcome

Author: Yasmina Chouik, Claire Francoz, Eleonora De Martin, Olivier Guillaud, Armand Abergel, Mario Altieri, Louise Barbier, Camille Besch, Olivier Chazouillères, Filomena Conti, Christophe Corpechot, Sébastien Dharancy, François Durand, Christophe Duvoux, Jean Gugenheim, Jean Hardwigsen, Marie‐Noëlle Hilleret, Pauline Houssel‐Debry, Nassim Kamar, Anne Minello, Martine Neau‐Cransac, Georges‐Philippe Pageaux, Sylvie Radenne, Olivier Roux, Faouzi Saliba, Didier Samuel, Claire Vanlemmens, Marie‐Lorraine Woehl‐Jaegle, Vincent Leroy, Jean‐Charles Duclos‐Vallée, Jérôme Dumortier, Hospices Civils de Lyon (HCL), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Edouard Herriot [CHU - HCL], Clinique de la Sauvegarde [Lyon], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, Hôpital de Hautepierre [Strasbourg], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Henri Mondor [Créteil], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), and Fondation Léon Bouchut
Subjects: early infection, MESH: Liver Transplantation, immunosuppression, MESH: Humans, Hepatology, MESH: Hepatitis, Autoimmune, fulminant hepatitis, MESH: Adult, MESH: Retrospective Studies, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, survival, sepsis, MESH: Massive Hepatic Necrosis, MESH: Female, MESH: Sepsis
Abstract: Background and aims: Autoimmune hepatitis (AIH) is a rare indication (
Published: 2023
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10. Simplified care-pathway selection for nonspecialist practice

Author: Aliya Gulamhusein, Nora Cazzagon, Xavier Verhelst, Andrew Mason, Cyriel Y. Ponsioen, George N. Dalekos, Keith D. Lindor, Frederik Nevens, Palak J. Trivedi, Adriaan J. van der Meer, Kris V. Kowdley, Willem J Lammers, Olivier Chazouillères, Ana Lleo, Douglas Thorburn, Nikolaos K. Gatselis, Bettina E. Hansen, Carla F. Murillo Perez, Tony Bruns, Gideon M. Hirschfield, Pietro Invernizzi, Annarosa Floreani, Christophe Corpechot, Marco Carbone, Marlyn J. Mayo, Albert Parés, Pier Maria Battezzati, Harry L.A. Janssen, Gastroenterology & Hepatology, Murillo Perez, C, Gulamhusein, A, Carbone, M, Trivedi, P, van der Meer, A, Corpechot, C, Battezzati, P, Lammers, W, Cazzagon, N, Floreani, A, Pares, A, Nevens, F, Lleo, A, Mayo, M, Kowdley, K, Ponsioen, C, Dalekos, G, Gatselis, N, Thorburn, D, Mason, A, Janssen, H, Verhelst, X, Bruns, T, Lindor, K, Chazouilleres, O, Invernizzi, P, Hansen, B, Hirschfield, G, Gastroenterology and Hepatology, and Amsterdam Gastroenterology Endocrinology Metabolism
Subjects: Cholagogues and Choleretics, medicine.medical_specialty, Bilirubin, Risk management tools, Risk Assessment, chemistry.chemical_compound, Risk groups, Internal medicine, medicine, Care pathway, Humans, In patient, Hepatology, Liver Cirrhosis, Biliary, business.industry, Ursodeoxycholic Acid, Gastroenterology, Fibrosis stage, Middle Aged, Alkaline Phosphatase, pbc, Young age, chemistry, Critical Pathways, Alkaline phosphatase, business
Abstract: BACKGROUND: Opportunity to redefine the care journeys for those living with primary biliary cholangitis (PBC) includes facilitating access to enhanced (PBC-dedicated) programmes by nonspecialist risk 'flagging' of patients. OBJECTIVE: To develop a nonexpert PBC stratification tool to help care pathway choices (standard vs. enhanced) choices in PBC. METHODS: We included ursodeoxycholic acid-treated patients with PBC from the Global PBC Study Group. The performance of baseline and 1-year clinical markers with transplant-free survival was assessed to develop the 'ABA' tool using Age (A), Bilirubin (B), and Alkaline phosphatase (A). Added value of fibrosis estimation was assessed. RESULTS: 'ABA' classification mapped three risk groups (n = 2226): low [Age > 50 years, bilirubin ≤ 1 × ULN, alkaline phosphatase (ALP) ≤ 3 × ULN], high (Age ≤ 50 years, bilirubin > 1 × ULN, ALP > 3 × ULN), and intermediate (other). Transplant-free survival at 10 years in the low-, intermediate-, and high-risk groups were 89, 77, and 59% at baseline and 86, 76, and 40% at 1 year, respectively. We propose that high-risk patients at baseline be directly triaged to enhanced (PBC-dedicated) care and the remaining be reassessed at 1 year. Modelling showed after 1 year 46% patients were proposed to enhanced care and 54% to standard care. The 'ABA' mapped pathways facilitated identification of patients at risk based on a young age, as compared to traditional liver biochemical stratification. In patients proposed to standard care, estimated fibrosis stage had ongoing prognostic value. CONCLUSION: Nonspecialist use of the 'ABA' risk tool could prioritize care journey choices for patients with PBC.
Published: 2021

11. Liver stiffness measurement by vibration-controlled transient elastography improves outcome prediction in primary biliary cholangitis

Author: Christophe Corpechot, Fabrice Carrat, Farid Gaouar, Frederic Chau, Gideon Hirschfield, Aliya Gulamhusein, Aldo J. Montano-Loza, Ellina Lytvyak, Christoph Schramm, Albert Pares, Ignasi Olivas, John E. Eaton, Karim T. Osman, George Dalekos, Nikolaos Gatselis, Frederik Nevens, Nora Cazzagon, Alessandra Zago, Francesco Paolo Russo, Nadir Abbas, Palak Trivedi, Douglas Thorburn, Francesca Saffioti, Laszlo Barkai, Davide Roccarina, Vicenza Calvaruso, Anna Fichera, Adèle Delamarre, Esli Medina-Morales, Alan Bonder, Vilas Patwardhan, Cristina Rigamonti, Marco Carbone, Pietro Invernizzi, Laura Cristoferi, Adriaan van der Meer, Rozanne de Veer, Ehud Zigmond, Eyal Yehezkel, Andreas E. Kremer, Ansgar Deibel, Jérôme Dumortier, Tony Bruns, Karsten Große, Georges-Philippe Pageaux, Aaron Wetten, Jessica Dyson, David Jones, Olivier Chazouillères, Bettina Hansen, Victor de Lédinghen, Corpechot, Christophe, Carrat, Fabrice, Gaouar, Farid, Chau, Frederic, Hirschfield, Gideon, Gulamhusein, Aliya, Montano-Loza, Aldo J, Lytvyak, Ellina, Schramm, Christoph, Pares, Albert, Olivas, Ignasi, Eaton, John E, Osman, Karim T, Dalekos, George, Gatselis, Nikolao, Nevens, Frederik, Cazzagon, Nora, Zago, Alessandra, Russo, Francesco Paolo, Abbas, Nadir, Trivedi, Palak, Thorburn, Dougla, Saffioti, Francesca, Barkai, Laszlo, Roccarina, Davide, Calvaruso, Vincenza, Fichera, Anna, Delamarre, Adèle, Medina-Morales, Esli, Bonder, Alan, Patwardhan, Vila, Rigamonti, Cristina, Carbone, Marco, Invernizzi, Pietro, Cristoferi, Laura, van der Meer, Adriaan, de Veer, Rozanne, Zigmond, Ehud, Yehezkel, Eyal, Kremer, Andreas E, Deibel, Ansgar, Dumortier, Jérôme, Bruns, Tony, Große, Karsten, Pageaux, Georges-Philippe, Wetten, Aaron, Dyson, Jessica, Jones, David, Chazouillères, Olivier, Hansen, Bettina, de Lédinghen, Victor, Corpechot, C, Carrat, F, Gaouar, F, Chau, F, Hirschfield, G, Gulamhusein, A, Montano-Loza, A, Lytvyak, E, Schramm, C, Pares, A, Olivas, I, Eaton, J, Osman, K, Dalekos, G, Gatselis, N, Nevens, F, Cazzagon, N, Zago, A, Russo, F, Abbas, N, Trivedi, P, Thorburn, D, Saffioti, F, Barkai, L, Roccarina, D, Calvaruso, V, Fichera, A, Delamarre, A, Medina-Morales, E, Bonder, A, Patwardhan, V, Rigamonti, C, Carbone, M, Invernizzi, P, Cristoferi, L, van der Meer, A, de Veer, R, Zigmond, E, Yehezkel, E, Kremer, A, Deibel, A, Dumortier, J, Bruns, T, Große, K, Pageaux, G, Wetten, A, Dyson, J, Jones, D, Chazouillères, O, Hansen, B, de Lédinghen, V, and Gastroenterology & Hepatology
Subjects: Liver Cirrhosis, FibroScan, Mortality, PBC, Prognosis, Transplantation, Hepatology, Prognosi, Liver Cirrhosis, Biliary, Liver Cirrhosi, Vibration, Follow-Up Studie, Cohort Studies, Liver, Elasticity Imaging Technique, Retrospective Studie, Humans, Elasticity Imaging Techniques, Cohort Studie, Retrospective Studies, Follow-Up Studies, Human
Abstract: BACKGROUND & AIMS: Liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) has been shown to predict outcomes of patients with primary biliary cholangitis (PBC) in small-size studies. We aimed to validate the prognostic value of LSM in a large cohort study. METHODS: We performed an international, multicentre, retrospective follow-up study of 3,985 patients with PBC seen at 23 centres in 12 countries. Eligibility criteria included at least 1 reliable LSM by VCTE and a follow-up ≥ 1 year. Independent derivation (n = 2,740) and validation (n = 568) cohorts were built. The primary endpoint was time to poor clinical outcomes defined as liver-related complications, liver transplantation, or death. Hazard ratios (HRs) with CIs were determined using a time-dependent multivariable Cox regression analysis. RESULTS: LSM was independently associated with poor clinical outcomes in the derivation (5,324 LSMs, mean follow-up 5.0 ± 3.1 years) and validation (1,470 LSMs, mean follow-up 5.0 ± 2.8 years) cohorts: adjusted HRs (95% CI) per additional kPa were 1.040 (1.026-1.054) and 1.042 (1.029-1.056), respectively (p
Published: 2022

12. Association of bezafibrate with transplant-free survival in patients with primary biliary cholangitis

Author: Kosuke Matsumoto, Bettina E. Hansen, Hajime Takikawa, Toshiaki Nakano, Olivier Chazouillères, Atsushi Tanaka, Fabrice Carrat, Junko Hirohara, Christophe Corpechot, Teikyo University School of Medicine, Kansai Medical University, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Référence des Maladies Rares - Maladies Inflammatoires des Voies Biliaires et Service d’Hépatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), University of Toronto, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de santé publique [CHU Saint-Antoine], and HAL-SU, Gestionnaire
Subjects: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Liver transplantation, Lower risk, Gastroenterology, Cohort Studies, Japan, Internal medicine, medicine, Humans, Proportional Hazards Models, Retrospective Studies, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Hepatology, Liver Cirrhosis, Biliary, business.industry, Hazard ratio, Retrospective cohort study, Middle Aged, Prognosis, Ursodeoxycholic acid, Transplantation, Treatment Outcome, Cohort, Number needed to treat, Female, Bezafibrate, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: A beneficial effect of bezafibrate (BZF) on symptoms and biochemical features of primary biliary cholangitis (PBC) has been reported in patients with an incomplete response to ursodeoxycholic acid (UDCA), but long-term effects on survival remain unknown. In Japan, BZF has been used as a de facto second-line therapy for PBC since 2000. Herein, we compared the survival rates between patients treated with and those without BZF in a large nationwide Japanese PBC cohort.All consecutively registered patients of this cohort who started UDCA therapy from 2000 onwards and had a follow-up ≥1 year were included. Association between BZF exposure and mortality or need for liver transplantation (LT) was assessed using time-dependent, multivariable-and propensity score-adjusted Cox proportional hazards models. Clinical benefit was quantified using the number needed to treat (NNT).Of 3,908 eligible patients, 3,162 (81%) received UDCA only and 746 (19%) UDCA and BZF over 17,360 and 3,932 patient-years, respectively. During follow-up, 183 deaths (89 liver-related) and 21 LT were registered. Exposure to combination therapy was associated with a significant decrease in all-cause and liver-related mortality or need for LT (adjusted hazard ratios: 0.3253, 95% CI 0.1936-0.5466 and 0.2748, 95% CI 0.1336-0.5655, respectively; p0.001 for both). This association was consistent across various risk groups at baseline. The NNTs with combination therapy to prevent 1 additional death or LT over 5, 10, and 15 years were 29 (95% CI 22-46), 14 (10-22), and 8 (6-15), respectively.In a large retrospective cohort study of treatment effects in patients with PBC, the addition of BZF to UDCA was associated with improved prognosis.The long-term efficacy of bezafibrate (BZF) on liver transplantation (LT) - free survival in patients with PBC and an incomplete response to ursodeoxycholic acid (UDCA) remains to be determined. In this Japanese nationwide retrospective cohort study, the use of UDCA-BZF combination therapy, compared to UDCA alone, was associated with a lower risk of all-cause and liver-related mortality or need for LT. These results indicate that BZF is so far the only drug in PBC to have demonstrated efficacy in improving symptoms, biochemical markers, and long-term outcomes.
Published: 2021
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13. A consensus integrated care pathway for patients with primary biliary cholangitis: a guideline-based approach to clinical care of patients

Author: Gideon M. Hirschfield, Femi Adekunle, Marco Carbone, Olivier Chazouillères, Helena Cortez-Pinto, Guilherme Macedo, Victor de Ledinghen, University Health Network, University of Toronto, Service d'hépatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Centre de Référence des Maladies Rares - Maladies Inflammatoires des Voies Biliaires et Service d’Hépatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Universidade de Lisboa (ULISBOA), Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Hirschfield, G, Chazouilleres, O, Cortez-Pinto, H, Macedo, G, de Ledinghen, V, Adekunle, F, Carbone, M, Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Universidade de Lisboa = University of Lisbon (ULISBOA), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Gestionnaire, Hal Sorbonne Université, and Repositório da Universidade de Lisboa
Subjects: ursodeoxycholic acid (udca), medicine.medical_specialty, Consensus, Cirrhosis, [SDV]Life Sciences [q-bio], Best practice, Risk Assessment, digestive system, Care provision, Patient Care Planning, obeticholic acid (oca), 03 medical and health sciences, Liver disease, 0302 clinical medicine, medicine, Humans, American association for the study of liver diseases (aasld), Clinical care, skin and connective tissue diseases, Intensive care medicine, european association for the study of the liver (easl), 030304 developmental biology, 0303 health sciences, Hepatology, Delivery of Health Care, Integrated, Liver Cirrhosis, Biliary, patient care pathway, business.industry, Gastroenterology, Guideline, medicine.disease, primary biliary cholangitis (pbc), digestive system diseases, Patient Care Management, 3. Good health, Integrated care, [SDV] Life Sciences [q-bio], Practice Guidelines as Topic, Critical Pathways, 030211 gastroenterology & hepatology, Cholestatic liver disease, business
Abstract: © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way, Introduction: Primary biliary cholangitis (PBC) is an infrequent, immune-mediated cholestatic liver disease, which can lead to liver fibrosis, cirrhosis and complications of end-stage liver disease. The established goals of treatment of PBC are prevention of end-stage liver disease and amelioration of associated symptoms. The European Association for the Study of the Liver (EASL) management guidelines provide extensive recommendations on the diagnosis and management of PBC. Areas covered: This article describes the development by expert consensus of a 'PBC Integrated Patient Care Pathway' to simplify and standardize the management of PBC for clinicians based on current practice. Expert opinion: Guideline adoption is potentially poor in practice since most patients with PBC in the community are seen by general gastroenterologists or hepatologists without a special interest in autoimmune liver disease. The PBC Integrated Patient Care Pathway is a best practice tool for clinicians designed to complement the EASL Clinical Practice Guidelines for the diagnosis and management of PBC patients. It gives clinicians a practical decision tree of the key steps in PBC management, thereby providing a simplified framework and an opportunity for more uniform practice that supports the safe and timely adoption of varied models of care provision to patients with PBC.
Published: 2021
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14. Liver Stiffness by Transient Elastography to Detect Porto‐Sinusoidal Vascular Liver Disease With Portal Hypertension

Author: Elkrief, Laure, Lazareth, Marie, Chevret, Sylvie, Paradis, Valérie, Magaz, Marta, Blaise, Lorraine, Rubbia‐Brandt, Laura, Moga, Lucile, Durand, François, Payancé, Audrey, Plessier, Aurélie, Chaffaut, Cendrine, Valla, Dominique, Malphettes, Marion, Diaz, Alba, Nault, Jean‐Charles, Nahon, Pierre, Audureau, Etienne, Ratziu, Vlad, Castera, Laurent, Garcia Pagan, Juan‐Carlos, Ganne‐Carrie, Nathalie, Rautou, Pierre‐Emmanuel, Marcellin, Patrick, Guyader, Dominique, Pol, Stanislas, Fontaine, Hélène, Larrey, Dominique, De Lédinghen, Victor, Ouzan, Denis, Zoulim, Fabien, Roulot, Dominique, Tran, Albert, Bronowicki, Jean‐Pierre, Zarski, Jean‐Pierre, Leroy, Vincent, Riachi, Ghassan, Calès, Paul, Péron, Jean‐Marie, Alric, Laurent, Bourlière, Marc, Mathurin, Philippe, Dharancy, Sebastien, Blanc, Jean‐Frédéric, Abergel Olivier Chazouillères, Armand, Mallat, Ariane, Grangé, Jean‐Didier, Attali, Pierre, Bacq, Yannick, Wartelle, Claire, Dao, Thông, Thabut, Dominique, Pilette, Christophe, Silvain, Christine, Christidis, Christos, Nguyen‐Khac, Eric, Bernard‐Chabert, Brigitte, Zucman, David, and Di Martino, Vincent
Subjects: 0301 basic medicine, medicine.medical_specialty, Cirrhosis, Hepatology, business.industry, Hepatitis C virus, Fatty liver, medicine.disease, medicine.disease_cause, Gastroenterology, 03 medical and health sciences, Liver disease, 030104 developmental biology, 0302 clinical medicine, Esophageal varices, Internal medicine, Ascites, medicine, Portal hypertension, 030211 gastroenterology & hepatology, medicine.symptom, Transient elastography, business
Abstract: Background & aims Porto-sinusoidal vascular liver disease (PSVD) is a rare cause of portal hypertension. PSVD is still often misdiagnosed as cirrhosis, emphasizing the need to improve PSVD diagnosis strategies. Data on liver stiffness measurement (TE-LSM) using transient elastography, in PSVD are limited. The aim of this study was to evaluate the accuracy of TE-LSM to discriminate PSVD from cirrhosis in patients with signs of portal hypertension. Approach & results Retrospective multicenter study comparing TE-LSM in patients with PSVD, according to VALDIG criteria, to patients with compensated biopsy-proven cirrhosis related to alcohol (n=117), hepatitis C virus (HCV) infection (n=110) or non-alcoholic fatty liver disease (NAFLD) (n=46). All patients had at least one sign of portal hypertension among gastroesophageal varices, splenomegaly, porto-systemic collaterals, history of ascites or platelet count Conclusions This study including a total of 155 patients with PSVD and 273 patients with cirrhosis demonstrates that TE-LSM 20 kPa, PSVD is highly unlikely.
Published: 2021
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15. Early liver transplantation for corticosteroid non-responders with acute severe autoimmune hepatitis: The SURFASA score

Author: Olivier Chazouillères, Florent Artru, Eleonora De Martin, Philippe Mathurin, Camille Besch, Christophe Duvoux, François Durand, Odile Goria, Hélène Fontaine, Hélène Agostini, Isabelle Ollivier-Hourmand, Noemi Reboux, Olivier Roux, Filomena Conti, Nathalie Ganne-Carrié, Didier Samuel, Georges-Philippe Pageaux, Philippe Ichai, Marilyne Debette-Gratien, Christine Silvain, Alexandra Heurgue, Jean-Marie Peron, Sylvie Radenne, Jérôme Dumortier, Audrey Coilly, Pauline Houssel-Debry, Sandrine Barge, Marc Bourlière, Pascal Potier, Jean-Charles Duclos-Vallée, Vincent Di Martino, Mylène Sebagh, and Victor de Ledinghen
Subjects: 0301 basic medicine, medicine.medical_specialty, Multivariate analysis, Hepatology, medicine.drug_class, Bilirubin, business.industry, medicine.medical_treatment, Odds ratio, Autoimmune hepatitis, Liver transplantation, medicine.disease, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, chemistry, Internal medicine, medicine, Corticosteroid, 030211 gastroenterology & hepatology, Prospective cohort study, business, Survival rate
Abstract: Background & Aims In acute severe autoimmune hepatitis (AS-AIH), the optimal timing for liver transplantation (LT) remains controversial. The objectives of this study were to determine early predictive factors for a non-response to corticosteroids and to propose a score to identify patients in whom LT is urgently indicated. Methods This was a retrospective, multicenter study (2009-2016). A diagnosis of AS-AIH was based on: i) Definite or probable AIH based on the simplified IAIHG score; ii) international normalized ratio (INR) ≥1.5 and/or bilirubin >200 μmol/L; iii) No previous history of AIH; iv) Histologically proven AIH. A treatment response was defined as LT-free survival at 90 days. The evolution of variables from corticosteroid initiation (day-D0) to D3 was estimated from: Δ%3 = (D3–D0)/D0. Results A total of 128 patients were included, with a median age of 52 (39–62) years; 72% were female. Overall survival reached 88%. One hundred and fifteen (90%) patients received corticosteroids, with a LT-free survival rate of 66% at 90 days. Under multivariate analysis, D0-INR (odds ratio [OR] 6.85; 95% CI 2.23–21.06; p Conclusion In patients with AS-AIH, INR at the introduction of corticosteroids and the evolution of INR and bilirubin are predictive of LT or death. Within 3 days of initiating corticosteroids, the SURFASA score can identify non-responders who require a referral for LT. This score needs to be validated in a prospective cohort. Lay summary The management of patients with acute severe autoimmune hepatitis is highly challenging, particularly regarding their early referral for liver transplantation. We found that international normalized ratio at the initiation of corticosteroid therapy and the evolution of international normalized ratio and bilirubin values after 3 days of therapy were highly predictive of liver transplantation or death. We are thus proposing a score that combines these variables and identifies patients in whom liver transplantation is urgently required.
Published: 2021
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16. Making Sense of Overlap and Crossover Syndromes

Author: Olivier Chazouillères
Subjects: medicine.medical_specialty, business.industry, Internal medicine, Sense (molecular biology), Crossover, medicine, Autoimmune hepatitis, medicine.disease, business, Gastroenterology, Ursodeoxycholic acid, medicine.drug, Primary sclerosing cholangitis
Published: 2020
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17. Long-term impact of preventive UDCA therapy after transplantation for primary biliary cholangitis

Author: Gideon M. Hirschfield, Maryam Ebadi, Xavier Verhelst, Federica Malinverno, Nora Cazzagon, Pierre Belnou, Christophe Corpechot, Falk Rauchfuss, Olivier Boillot, Raoul Poupon, Jérôme Dumortier, Palak J. Trivedi, Maria Francesca Donato, Sascha Chopra, Dennis Eurich, Francesco Paolo Russo, Martina Sterneck, Aldo J. Montano-Loza, Maren H. Harms, Fabrice Carrat, Philipp A. Reuken, Christoph Schramm, Alexie Bosch, Albert Parés, Patrick McDowell, Davide Roccarina, Andrew Mason, Jorn C Goet, Bettina E. Hansen, Emiliano Giostra, Anna Reig, Annarosa Floreani, Dietmar Jacob, Douglas Thorburn, Olivier Chazouillères, Tony Bruns, Alessio Gerussi, Henk R. van Buuren, Filomena Conti, Frederik Nevens, Corpechot, C, Chazouilleres, O, Belnou, P, Montano-Loza, A, Mason, A, Ebadi, M, Eurich, D, Chopra, S, Jacob, D, Schramm, C, Sterneck, M, Bruns, T, Reuken, P, Rauchfuss, F, Roccarina, D, Thorburn, D, Gerussi, A, Trivedi, P, Hirschfield, G, Mcdowell, P, Nevens, F, Boillot, O, Bosch, A, Giostra, E, Conti, F, Poupon, R, Pares, A, Reig, A, Donato, M, Malinverno, F, Floreani, A, Russo, F, Cazzagon, N, Verhelst, X, Goet, J, Harms, M, van Buuren, H, Hansen, B, Carrat, F, Dumortier, J, Gastroenterology & Hepatology, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Graft Rejection, Male, 0301 basic medicine, Cholagogues and Choleretics, Cirrhosis, Survival, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Placebo-controlled study, Liver transplantation, PBC, Gastroenterology, UDCA, 0302 clinical medicine, MED/12 - GASTROENTEROLOGIA, Recurrence, Liver Cirrhosis, Biliary, Ursodeoxycholic Acid, Hazard ratio, Middle Aged, Ursodeoxycholic acid, 3. Good health, Survival Rate, Treatment Outcome, Tacrolimu, Cyclosporine, Tacrolimus, Transplantation, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, Immunosuppressive Agents, medicine.drug, Risk, medicine.medical_specialty, 03 medical and health sciences, Internal medicine, medicine, Humans, Aged, Retrospective Studies, Hepatology, business.industry, Retrospective cohort study, medicine.disease, digestive system diseases, Liver Transplantation, Regimen, 030104 developmental biology, MED/09 - MEDICINA INTERNA, business, Follow-Up Studies
Abstract: Background & Aims: Recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT) is frequent and can impair graft and patient survival. Ursodeoxycholic acid (UDCA) is the current standard therapy for PBC. We investigated the effect of preventive exposure to UDCA on the incidence and long-term consequences of PBC recurrence after LT. Methods: We performed a retrospective cohort study in 780 patients transplanted for PBC, between 1983–2017 in 16 centers (9 countries), and followed-up for a median of 11 years. Among them, 190 received preventive UDCA (10–15 mg/kg/day). The primary outcome was histological evidence of PBC recurrence. The secondary outcomes were graft loss, liver-related death, and all-cause death. The association between preventive UDCA and outcomes was quantified using multivariable-adjusted Cox and restricted mean survival time (RMST) models. Results: While recurrence of PBC significantly shortened graft and patient survival, preventive exposure to UDCA was associated with reduced risk of PBC recurrence (adjusted hazard ratio [aHR] 0.41; 95% CI 0.28–0.61; p
Published: 2020
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18. [Primary biliary cholangitis]

Author: Pierre-Antoine, Soret, Olivier, Chazouillères, and Christophe, Corpechot
Subjects: Cholangitis, Liver Cirrhosis, Biliary, Pruritus, Ursodeoxycholic Acid, Humans, Female, Autoimmune Diseases
Abstract: PRIMARY BILIARY CHOLANGITIS Primary biliary cholangitis (formally primary biliary cirrhosis, PBC) is the most common chronic cholestatic liver disease in humans. It is a presumed autoimmune liver disease, characterized by inflammation and progressive destruction of small bile ducts. Without treatment, PBC progresses towards liver fibrosis and, ultimately, cirrhosis. Women older than 40 are more likely affected. Pruritus and tiredness are the most common symptoms but they are frequently lacking. Diagnosis is made by the association of chronic biochemical features of cholestasis (parallel increase in ALP and GGT) and presence of specific auto-antibodies (particularly M2 anti-mitochondrial antibodies). Ursodeoxycholic acid (UDCA), which is the standard of care treatment for PBC, has dramatically improved the prognosis of the disease. However, 30 % to 40 % of patients have an inadequate biochemical response to UDCA and continue to be at high-risk of complications. In this situation, second-line treatments, including obeticholic acid or fibrates, should be considered in association with UDCA.CHOLANGITE BILIAIRE PRIMITIVE La cholangite biliaire primitive (ou anciennement cirrhose biliaire primitive, CBP) est la maladie cholestatique chronique la plus fréquente. Il s’agit d’une affection présumée auto-immune caractérisée par une inflammation et une destruction progressive des petits canaux biliaires, aboutissant, en l’absence de traitement, à une fibrose hépatique puis à une cirrhose. Elle atteint majoritairement les femmes (90 % des cas) de plus de 40 ans. Les signes cliniques révélateurs (prurit et asthénie) sont inconstants et peu spécifiques. Le diagnostic repose sur l’association d’une cholestase biologique (élévation concomitante des PAL et de la GGT) chronique et la présence d’auto-anticorps spécifiques (en particulier anti-mitochondrie de type 2). Le traitement de référence est l’acide ursodésoxycholique (AUDC) qui a fortement amélioré le pronostic de la CBP. Dans 30 à 40 % des cas, la réponse biologique à l’AUDC est insuffisante et des traitements complémentaires sont nécessaires, parmi lesquels figurent actuellement l’acide obéticholique et les fibrates.
Published: 2022

19. Impact of thiopurines and tumour necrosis factor antagonists on primary sclerosing cholangitis outcomes in patients with inflammatory bowel disease

Author: Amélie Biron, Laurent Beaugerie, Olivier Chazouillères, Julien Kirchgesner, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Pharmacoépidémiologie et évaluation des soins [iPLesp] (PEPITES), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Kirchgesner, Julien
Subjects: Hepatology, thiopurines, Cholangitis, Sclerosing, Gastroenterology, primary sclerosing cholangitis, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.CAN]Life Sciences [q-bio]/Cancer, anti-TNF, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Inflammatory Bowel Diseases, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Liver Transplantation, [SDV.CAN] Life Sciences [q-bio]/Cancer, Risk Factors, inflammatory bowel disease, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, biliary tract cancer, Humans, Pharmacology (medical), Tumor Necrosis Factor Inhibitors, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, Proportional Hazards Models, Retrospective Studies
Abstract: International audience; Background: Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) are at risk of biliary tract cancer and liver damage (possibly leading to liver transplantation), and are often treated for IBD with thiopurines and/or tumour necrosis factor antagonists (anti-TNF) on a long-term basis.Aims: To assess the risk of biliary tract cancer and liver transplantation in patients exposed to thiopurines and/or anti-TNF in a French nationwide cohort.Methods: We performed a population-based study of patients aged 18 years or older with PSC and IBD in the French national health insurance database. Patients were followed from 1 January 2009 to 31 December 2018. The risks of biliary tract cancer and liver transplantation associated with thiopurines and anti-TNF exposure were assessed with marginal structural Cox proportional hazard models, adjusting for baseline demographics and comorbidities, and time-varying medications and PSC activity.Results: Among the 1929 patients with PSC and IBD included, 37 biliary tract cancers and 83 liver transplantations occurred. Compared with patients not exposed to thiopurines or anti-TNF agents, patients exposed to thiopurines (hazard ratio [HR], 1.05; 95% confidence interval [CI], 0.39–2.82) or anti-TNF agents (HR, 0.59; 95% CI, 0.13–2.80) had no excess risk of biliary tract cancer. Similarly, patients exposed to thiopurines (HR, 0.67; 95% CI, 0.30–1.48) or anti-TNF agents (HR, 0.68; CI, 0.22–2.09) had no excess risk of liver transplantation.ConclusionsPatients with PSC and IBD who are exposed to thiopurines or anti-TNF agents are not at excess risk of biliary tract cancer or liver transplantation.
Published: 2022
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20. Protective potential of the gallbladder in primary sclerosing cholangitis

Author: Nora Cazzagon, Ester Gonzalez-Sanchez, Haquima El-Mourabit, Dominique Wendum, Dominique Rainteau, Lydie Humbert, Christophe Corpechot, Olivier Chazouillères, Lionel Arrivé, Chantal Housset, and Sara Lemoinne
Subjects: Magnetic resonance imaging, Hepatology, Gastroenterology, Internal Medicine, Immunology and Allergy, Abcb4 knockout mice, Bile acids, Cholecystectomy, Gallbladder volume
Published: 2022

21. Recurrence of primary sclerosing cholangitis after liver transplantation: a french cohort study including 571 patients

Author: Florian Veyre, Eleonora De Martin, Domitille Erard, Claire Francoz, Laure Elkrief, Camille Besch, Olivier Boillot, Karim Boudjema, Filomena Conti, Sebastien Dharancy, Christophe Duvoux, Jean Gugenheim, Jean Hardwigsen, Marie-Noëlle Hilleret, Isabelle Ollivier-Hourmand, Maryline Debette-Gratien, Pauline Houssel-Debry, Nassim Kamar, Jean-Baptiste Hiriart, Stéphanie Faure, Faouzi Saliba, Didier Samuel, Claire Vanlemmens, Christophe Corpechot, Olivier Chazouillères, and Jérôme Dumortier
Subjects: Hepatology
Published: 2022
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22. Non-invasive diagnosis and follow-up of primary sclerosing cholangitis

Author: Pascal Potier, Victor de Lédinghen, Christophe Bureau, Jérôme Gournay, Nathalie Ganne-Carrié, Florence Tanne, Charlotte Bouzbib, M. Bourlière, Alexandra Heurgue, Eric Nguyen-Khac, Olivier Chazouillères, and Bertrand Hanslik
Subjects: medicine.medical_specialty, Colorectal cancer, Biliary cirrhosis, Cholangitis, Sclerosing, digestive system, Gastroenterology, Inflammatory bowel disease, Primary sclerosing cholangitis, Cholangiography, Cholestasis, Internal medicine, medicine, Humans, Cholangiopancreatography, Endoscopic Retrograde, Endoscopic retrograde cholangiopancreatography, Hepatology, medicine.diagnostic_test, business.industry, medicine.disease, Inflammatory Bowel Diseases, digestive system diseases, Bile Ducts, Intrahepatic, Bile Duct Neoplasms, Sample collection, business, Follow-Up Studies
Abstract: Primary sclerosing cholangitis (PSC) is a rare and chronic cholestatic liver disease of unknown cause commonly associated with inflammatory bowel disease (IBD) and characterized by progressive obliterative fibro-inflammation of the biliary tree. Although the natural course is highly variable, PSC is often progressive, leading to biliary cirrhosis and its complications. In addition, PSC is a condition harbouring broad neoplastic potential with increased susceptibility for the development of both biliary and colon cancer. As in other chronic liver diseases, non-invasive methods play a major role in the diagnosis and monitoring of PSC. MR cholangiography is the key exam for the diagnosis and has replaced diagnostic endoscopic retrograde cholangiopancreatography (ERCP). A strict and standardised protocol for carrying out MR cholangiography is recommended. Liver stiffness measured by FibroScan® correlates with the degree of liver fibrosis, has a prognostic value and should be repeated during follow-up. Invasive methods still play an important role, especially ERCP which is indicated for therapeutic purposes or for endo-biliary sample collection in suspected cholangiocarcinoma (following discussion in a multidisciplinary team meeting) and total colonoscopy which is recommended at the initial diagnosis of any PSC and annually in patients with IBD.
Published: 2021

23. Genetic contribution of ABCC2 to Dubin‐Johnson syndrome and inherited cholestatic disorders

Author: Muriel Girard, Yves Chretien, Bertrand Roquelaure, Olivier Chazouillères, Catherine Dong, Véronique Barbu, Christophe Corpechot, Isabelle Jéru, Pierre Broué, Chantal Housset, and Olivier Lascols
Subjects: Adult, Male, Heterozygote, medicine.medical_specialty, Adolescent, DNA Copy Number Variations, Benign Recurrent Intrahepatic Cholestasis, Population, Cholestasis, Intrahepatic, Gastroenterology, Liver disorder, Cohort Studies, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Dubin–Johnson syndrome, Cholestasis, Pregnancy, Internal medicine, medicine, Humans, Neonatal cholestasis, Child, education, Genetic testing, education.field_of_study, Hepatology, medicine.diagnostic_test, Jaundice, Chronic Idiopathic, business.industry, Infant, Middle Aged, medicine.disease, Multidrug Resistance-Associated Protein 2, Pregnancy Complications, Child, Preschool, 030220 oncology & carcinogenesis, Mutation, Female, 030211 gastroenterology & hepatology, France, Multidrug Resistance-Associated Proteins, business, Cholestasis of pregnancy
Abstract: Background and aims The ABCC2 gene is implicated in Dubin-Johnson syndrome (DJS), a rare autosomal recessive liver disorder. The primary aim of this study was to determine the diagnostic value of ABCC2 genetic testing in the largest cohort of DJS reported to date. The high number of patients with cholestatic manifestations in this series prompted us to evaluate the genetic contribution of rare, potentially pathogenic ABCC2 variants to other inherited cholestatic disorders. Methods The cohort study included 32 patients with clinical DJS diagnosis, and 372 patients referred for the following disorders: low phospholipid-associated cholelithiasis (LPAC) syndrome, intrahepatic cholestasis of pregnancy (ICP) and benign recurrent intrahepatic cholestasis (BRIC). ABCC2 was screened by next-generation sequencing. Results Most patients with clinical DJS had positive genetic diagnosis (n = 30; 94%), with a great diversity of point mutations and copy number variations in ABCC2. Strikingly, eight (27%) of these patients showed transient cholestatic features at presentation: four neonatal cholestasis, two ICP, one contraceptive-induced cholestasis and one sporadic cholestasis. Conversely, the frequency of rare, heterozygous, potentially pathogenic ABCC2 variants in patients with LPAC, ICP or BRIC did not differ significantly from that of the general population. Conclusions This large series reveals that DJS is a highly homogeneous Mendelian disorder involving a large spectrum of ABCC2 variants. Genetic testing is crucial to establish early DJS diagnosis in patients with atypical presentations, such as neonatal cholestasis. This study also provides no evidence for the contribution of rare, potentially pathogenic ABCC2 variants to other inherited cholestatic disorders.
Published: 2019
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24. MRCP+TM-derived biliary metrics are associated with disease severity and clinical outcomes in patients with primary sclerosing cholangitis

Author: Nora Cazzagon, Sanaa El Mouhadi, Quentin Vanderbecq, Carlos Ferreira, Sara Lemoinne, Christophe Corpechot, Olivier Chazouillères, and Lionel Arrivè
Subjects: Hepatology
Published: 2022
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25. Predictive Factors for Hepatocellular Carcinoma in Chronic Hepatitis B Using Structural Equation Modeling: A Prospective Cohort Study

Author: Jean-Pierre Bronowicki, Clovis Lusivika-Nzinga, Jean-Charles Duclos-Vallée, Ghassan Riachi, Anne Minello, Thomas Decaens, Louis d’Alteroche, Fabrice Carrat, Isabelle Portal, François Raffi, Fabien Zoulim, Sophie Metivier, Véronique Loustaud-Ratti, François Habersetzer, Jérôme Gournay, Olivier Chazouillères, Paul Calès, Victor de Ledinghen, Xavier Causse, Stanislas Pol, Céline Dorival, Isabelle Rosa, Dominique Larrey, Tarik Asselah, Marc Bourlière, Claire Geist, Nathanael Lapidus, Laurent Lam, Moana Gelu-Simeon, Laurent Alric, Vincent Leroy, Hélène Fontaine, Armand Abergel, Nathalie Ganne, Dominique Thabut, Philippe Mathurin, Albert Tran, Dominique Guyader, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Saint-Joseph [Marseille], Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Interactions Virus-Hôte et Maladies Hépatiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Virologie, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, CRHU Nancy, Physiopathologie des Maladies Inflammatoires de l'Intestin, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHI Créteil, Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Régional d'Orléans (CHRO), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'hépatologie [CHU Saint-Antoine], CHU Pointe-à-Pitre/Abymes [Guadeloupe], Institut de recherche en santé, environnement et travail (Irset), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), CHU Toulouse [Toulouse], Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), CHU Rouen, Normandie Université (NU), Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital de la Timone [CHU - APHM] (TIMONE), Immunité Innée - Innate Immunity, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], The ANRS CO22 HEPATHER cohort is sponsored and funded by INSERM‐ANRS and conducted in collaboration with Association Française pour l'étude du Foie (AFEF). The cohort received supports from ANR (Agence Nationale de la Recherche), DGS (Direction Générale de la Santé), MSD, Janssen, Gilead, Abbvie, BMS, and Roche., Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Pathologies biliaires, fibrose et cancer du foie [CRSA], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: Male, Liver Cancer, medicine.medical_specialty, Hepatocarcinogenesis, Hepatitis B virus, Carcinoma, Hepatocellular, Epidemiology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Liver transplantation, Sciences du Vivant [q-bio]/Cancer, medicine.disease_cause, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Hepatitis B, Chronic, [SDV.CAN] Life Sciences [q-bio]/Cancer, Risk Factors, Internal medicine, medicine, Humans, Prospective Studies, Prospective cohort study, Aged, Hepatology, business.industry, Liver Neoplasms, Carcinoma, Hepatocellular, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, digestive system diseases, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Cohort, 030211 gastroenterology & hepatology, Metabolic syndrome, business, Liver cancer
Abstract: International audience; BACKGROUND and AIMS: The factors predicting hepatocellular carcinoma (HCC) occurrence in chronic hepatitis B need to be precisely known to improve its detection. We identified pathways and individual predictive factors associated with HCC in the ANRS CO22 HEPATHER cohort. METHODS: The study analyzed HBV-infected patients recruited at 32 French expert hepatology centers from August 6, 2012, to December 31, 2015. We excluded patients with chronic HCV, HDV and a history of HCC, decompensated cirrhosis or liver transplantation. Structural equation models were developed to characterize the causal pathways leading to HCC occurrence. The association between clinical characteristics (age, gender, body-mass index, liver fibrosis, alcohol consumption, smoking status, diabetes, hypertension, dyslipidemia, alpha-fetoprotein, HBV DNA levels, antiviral therapy) and incident HCC was quantified. RESULTS: Among the 4,489 patients included, 33 patients reported incident HCC. The median follow-up was 45.2 months. Age (β = 0.18 by decade, 95% CI 0.14-0.23), male gender (β = 0.23, 95% CI 0.18-0.29), metabolic syndrome (β = 0.28, 95% CI 0.22-0.33), alcohol consumption (β = 0.09, 95% CI 0.05-0.14) and HBV DNA (β = 0.25, 95% CI 0.17-0.34) had a significant and direct effect on the occurrence of advanced liver fibrosis. Liver fibrosis (β = 0.71, 95% CI 0.55-0.87) predicted, in turn, the occurrence of HCC. CONCLUSIONS: Liver fibrosis mediates the effects of age, gender, alcohol, metabolic syndrome and HBV DNA on the occurrence of HCC. Elderly men with chronic hepatitis B, risky alcohol use, advanced liver fibrosis, metabolic syndrome and high HBV DNA levels should be monitored closely to detect the development of HCC.
Published: 2021
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26. Assessment of hepatic steatosis by controlled attenuation parameter using the M and XL probes:an individual patient data meta-analysis

Author: Emmanuel Tsochatzis, Olivier Chazouillères, Jeremy F. L. Cobbold, Stephan Baumeler, Sylvie Naveau, Thomas Karlas, Maja Thiele, Vincent Wai-Sun Wong, David Semela, Gabriel Perlemuter, Harshit Garg, Cristiane A. Villela-Nogueira, Magali Sasso, Marie Irles-Depe, Monica Lupsor-Platon, Peter J Eddowes, David Sheridan, Cosmin Sebastian Voican, Aleksander Krag, Johannes Wiegand, Shalimar, Sebastian Mueller, Philip N. Newsome, Victor de Ledinghen, Michael Allison, Sandeep Aggarwal, Quentin M. Anstee, Wah-Kheong Chan, David Petroff, A.C. Cardoso, Valentin Blank, and Grace Lai-Hung Wong
Subjects: Adult, Male, medicine.medical_specialty, Biopsy, MEDLINE, Severity of Illness Index, Body Mass Index, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Internal medicine, Severity of illness, medicine, Humans, Hepatology, Receiver operating characteristic, business.industry, Fatty liver, Gastroenterology, Middle Aged, medicine.disease, 3. Good health, Liver, ROC Curve, 030220 oncology & carcinogenesis, Meta-analysis, Area Under Curve, Elasticity Imaging Techniques, 030211 gastroenterology & hepatology, Female, Steatosis, business, Body mass index
Abstract: BACKGROUND: Diagnostic tools for liver disease can now include estimation of the grade of hepatic steatosis (S0 to S3). Controlled attenuation parameter (CAP) is a non-invasive method for assessing hepatic steatosis that has become available for patients who are obese (FibroScan XL probe), but a consensus has not yet been reached regarding cutoffs and its diagnostic performance. We aimed to assess diagnostic properties and identify relevant covariates with use of an individual patient data meta-analysis.METHODS: We did an individual patient data meta-analysis, in which we searched PubMed and Web of Science for studies published from database inception until April 30, 2019. Studies reporting original biopsy-controlled data of CAP for non-invasive grading of steatosis were eligible. Probe recommendation was based on automated selection, manual assessment of skin-to-liver-capsule distance, and a body-mass index (BMI) criterion. Receiver operating characteristic methods and mixed models were used to assess diagnostic properties and covariates. Patients with non-alcoholic fatty liver disease (NAFLD) were analysed separately because they are the predominant patient group when using the XL probe. This study is registered with PROSPERO, CRD42018099284.FINDINGS: 16 studies reported histology-controlled CAP including the XL probe, and individual data from 13 papers and 2346 patients were included. Patients with a mean age of 46·5 years (SD 14·5) were recruited from 20 centres in nine countries. 2283 patients had data for BMI; 673 (29%) were normal weight (BMI INTERPRETATION: CAP cutoffs varied according to cause, and can effectively recognise significant steatosis in patients with viral hepatitis. CAP cannot grade steatosis in patients with NAFLD adequately, but its value in a NAFLD screening setting needs to be studied, ideally with methods beyond the traditional histological reference standard.FUNDING: The German Federal Ministry of Education and Research and Echosens.
Published: 2021
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27. Overlap Syndromes

Author: Nora Cazzagon and Olivier Chazouillères
Published: 2021
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28. Low-phospholipid-associated cholelithiasis syndrome: Prevalence, clinical features, and comorbidities

Author: Bertrand Condat, Yves Chrétien, Magalie Picon-Coste, Olivier Chazouillères, David Zanditenas, Lionel Arrivé, Chantal Housset, Pascal Potier, Karima Ben Belkacem, Farid Gaouar, Catherine Dong, Marie-Pierre Hauuy, Raoul Poupon, Anware Maftouh, Véronique Barbu, Christophe Corpechot, Béatrice Noblinski, HAL-SU, Gestionnaire, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Référence des Maladies Rares - Maladies Inflammatoires des Voies Biliaires et Service d’Hépatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Radiologie [CHU Saint-Antoine], Hôpital Saint Camille, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Physiopathologie des maladies génétiques d'expression pédiatrique (UMRS_933), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: Pediatrics, medicine.medical_specialty, FDR, false discovery rate, medicine.medical_treatment, CBD, common bile duct, UDCA, ursodeoxycholic acid, 03 medical and health sciences, 0302 clinical medicine, Cholestasis, Pregnancy, Internal Medicine, Immunology and Allergy, Medicine, LPAC, Young adult, Family history, lcsh:RC799-869, ICP, intrahepatic cholestasis of pregnancy, MRCP, magnetic resonance cholangiopancreatography, 030304 developmental biology, Cancer, 0303 health sciences, Endoscopic retrograde cholangiopancreatography, Hepatology, medicine.diagnostic_test, LPAC, low-phospholipid-associated cholelithiasis, business.industry, GGT, gamma-glutamyltransferase, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Gallstones, ABCB4, medicine.disease, Metabolic syndrome, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Cholecystitis, 030211 gastroenterology & hepatology, Cholecystectomy, lcsh:Diseases of the digestive system. Gastroenterology, ABCB4, ATP-binding cassette subfamily B member 4, business, Research Article, ERCP, endoscopic retrograde cholangiopancreatography
Abstract: Background & Aims Low-phospholipid-associated cholelithiasis (LPAC) syndrome, a rare genetic form of intrahepatic cholelithiasis in adults, is still poorly understood. We report the results of the largest-ever case-control study of patients with LPAC syndrome aiming to assess the prevalence, clinical features, and comorbidities of the disease. Methods We included all LPAC cases diagnosed between 2001 and 2016 in 11 French centres. Controls consisted of all patients who underwent a cholecystectomy for common gallstone disease in a single non-academic centre over 1 year. A logistic regression analysis was used to identify the clinical features associated with LPAC syndrome across several patient strata with increasing levels of diagnostic confidence. The ratio between the incident cases of LPAC syndrome and the total number of cholecystectomies for gallstones was used to assess the relative prevalence of the disease. Results In this study, 308 cases and 206 controls were included. LPAC syndrome accounted for 0.5–1.9% of all patients admitted with symptomatic gallstone disease. Age at first symptoms, Graphical abstract, Highlights • Low-phospholipid-associated cholelithiasis (LPAC) syndrome affects approximately 1% of adults with symptomatic cholelithiasis. • Normal weight, common bile duct stones, and lack of cholecystitis are clinical features significantly associated with this syndrome. • ABCB4 variants in patients with LPAC may be associated with an increased personal or family risk of hepato-biliary cancer.
Published: 2021
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29. Combination of fibrates with obeticholic acid is able to normalise biochemical liver tests in patients with difficult-to-treat primary biliary cholangitis

Author: Pietro Invernizzi, Dominique Larrey, Thomas Berg, Christine Silvain, Christina Weiler-Normann, Rodolphe Anty, Cervoni Jp, Albert Parés, Cynthia Levy, Olivier Chazouillères, Laurent Lam, Christophe Bureau, Isabelle Rosa-Hezode, Palak J. Trivedi, Christoph Schramm, Nora Cazzagon, Laurent Alric, Vincent Leroy, Alexandra Heurgué, Frederik Nevens, Jérôme Dumortier, Pierre Antoine Soret, Olivier Roux, Marco Carbone, Fabrice Carrat, Pascal Potier, Lena Smets, Christophe Corpechot, Gestionnaire, Hal Sorbonne Université, Centre de Référence des Maladies Rares - Maladies Inflammatoires des Voies Biliaires et Service d’Hépatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de santé publique [CHU Saint-Antoine], University Hospitals Leuven [Leuven], Leipzig University, Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Centre Hospitalier Universitaire [Grenoble] (CHU), University Hospitals Birmingham [Birmingham, Royaume-Uni], Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), University Hospital Hamburg-Eppendorf, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Centre Hospitalier Intercommunal de Créteil (CHIC), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Régional d'Orléans (CHRO), Centre de référence des Maladies Vasculaires du Foie [Paris] (FILFOIE), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), University of Miami Leonard M. Miller School of Medicine (UMMSM), Clinic Barcelona Hospital Universitari, Soret, P, Lam, L, Carrat, F, Smets, L, Berg, T, Carbone, M, Invernizzi, P, Leroy, V, Trivedi, P, Cazzagon, N, Weiler-Normann, C, Alric, L, Rosa-Hezode, I, Heurgue, A, Cervoni, J, Dumortier, J, Potier, P, Roux, O, Silvain, C, Bureau, C, Anty, R, Larrey, D, Levy, C, Pares, A, Schramm, C, Nevens, F, Chazouilleres, O, and Corpechot, C
Subjects: Liver Cirrhosis, medicine.medical_specialty, Cholagogues and Choleretics, Bilirubin, [SDV]Life Sciences [q-bio], Chenodeoxycholic Acid, Gastroenterology, chemistry.chemical_compound, Retrospective Studie, Internal medicine, Chenodeoxycholic acid, medicine, Humans, Pharmacology (medical), Cholagogues and Choleretic, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Bezafibrate, Fenofibrate, Hepatology, Liver Cirrhosis, Biliary, business.industry, Fibric Acids, Ursodeoxycholic Acid, Biliary, Obeticholic acid, Retrospective cohort study, Odds ratio, eye diseases, Ursodeoxycholic acid, Fibric Acid, [SDV] Life Sciences [q-bio], chemistry, business, Human, medicine.drug
Abstract: Background: Obeticholic acid (OCA) and fibrates are second-line therapies for patients with primary biliary cholangitis (PBC) with an inadequate response to ursodeoxycholic acid (UDCA). Aim: To know whether OCA and fibrates, administered together in combination with UDCA, have additive beneficial effects in patients with difficult-to-treat PBC. Methods: PBC patients treated for ≥3months with UDCA, OCA and fibrates (bezafibrate or fenofibrate) due to failure of either second-line therapy were included in a multicentre, uncontrolled retrospective cohort study. Changes in biochemical liver tests and pruritus were analysed using a generalised linear mixed-effect model. Results: Among 58 patients included, half received OCA as second-line and fibrates as third-line therapy (Group OCA-Fibrate), while the other half had the inverse therapeutic sequence (Group Fibrate-OCA). The mean duration of triple therapy was 11months (range 3-26). Compared to dual therapy, triple therapy was associated with a significant gain in alkaline phosphatase (ALP) reduction: 22% per first year (95% CI 12%-31%), an effect that was stronger in OCA-Fibrate than in Fibrate-OCA group. Triple therapy was associated with a 3.4 (95% CI 1.4-8.2) odds ratio (OR) of reaching normal ALP and with a significant decrease in gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin. The ORs of achieving the Paris-2 and Toronto criteria of adequate biochemical response were 6.8 (95% CI 2.8-16.7) and 9.2 (95% CI 3.4-25.1) respectively. Finally, triple therapy significantly improved pruritus in OCA-Fibrate but not in Fibrate-OCA group. Conclusions: Triple therapy with UDCA, OCA and fibrates is able to normalise biochemical liver tests and improve pruritus in patients with difficult-to-treat PBC.
Published: 2021
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30. Letter: the use of magnetic resonance scores (Anali) for risk stratification in PSC

Author: Lionel Arrivé, Christophe Corpechot, Nora Cazzagon, Sara Lemoinne, Olivier Chazouillères, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Università degli Studi di Padova = University of Padua (Unipd), and Lemoinne, Sara
Subjects: medicine.medical_specialty, Magnetic Resonance Spectroscopy, Hepatology, medicine.diagnostic_test, business.industry, Cholangiopancreatography, Magnetic Resonance, Cholangitis, Cholangitis, Sclerosing, Gastroenterology, Magnetic resonance imaging, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Prognosis, Risk Assessment, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Sclerosing, Cholangiopancreatography, Text mining, Risk stratification, Medicine, Humans, Pharmacology (medical), Radiology, Magnetic Resonance, business
Abstract: International audience; GBCA gadolinium-based contrast agent MR magnetic resonance MRC magnetic resonance cholangiography PSC primary sclerosing cholangitis VCTE vibration controlled transient elastography Dear editor, We read with interest the review written by Mahzar and Russo about non-invasive prognostic tests for primary sclerosing cholangitis (PSC) 1. Although rare, PSC is a serious disease, associated with potentially lethal complications, notably cirrhosis and cholangiocarcinoma 2. Liver transplantation is the only curative treatment for PSC and median transplant-free survival is approximately 12-21 years after diagnosis 3. Identification of prognostic factors is essential for tailoring the follow-up strategies and testing new therapeutic modalities in homogeneous groups of PSC patients. As detailed in this review, over the last twenty years, different teams across the world, including ours, have identified several noninvasive prognostic tests for PSC patients 1. First, our team demonstrated in a large retrospective study that liver stiffness measured by vibration-controlled transient elastography (VCTE) was an independent predictive marker of survival in PSC patients 4. Next, we built 2 magnetic resonance (MR) risk scores (with and without gadolinium-based contrast agent (GBCA) administration) 5 , called Anali scores, and showed that they were able to predict adverse outcome-free survival (defined by survival without liver transplantation or cirrhosis
Published: 2021
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31. Su1354: QUANTITATIVE MAGNETIC RESONANCE CHOLANGIOPANCREATOGRAPY METRICS SIGNIFICANTLY CORRELATE WITH DISEASE SEVERITY AND CLINICAL OUTCOMES IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS

Author: Nora Cazzagon, Sanaâ El Mouhadi, Quentin Vanderbecq, Carlos Ferreira, Sarah Finnegan, Sara Lemoinne, Christophe Corpechot, Olivier Chazouillères, and Lionel Arrivé
Subjects: Hepatology, Gastroenterology
Published: 2022
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32. Personalized surveillance for hepatocellular carcinoma in cirrhosis – using machine learning adapted to HCV status

Author: Jean-Marie Péron, Dominique Larrey, Albert Tran, Marc Bourlière, Paul Calès, Thong Dao, Eric Nguyen-Khac, Olivier Chazouillères, Brigitte Bernard-Chabert, Pierre Attali, Ghassan Riachi, Jean-Didier Grangé, Dominique Guyader, Pierre Nahon, Victor de Ledinghen, Claire Wartelle, Ariane Mallat, Christos Christidis, Christophe Pilette, Vincent Di Martino, Jean-Pierre Bronowicki, Stanislas Pol, Philippe Mathurin, Dominique Roulot, Denis Ouzan, Jean-Frédéric Blanc, Louis d’Alteroche, David Zucman, Jean-Pierre Zarski, Tarik Asselah, Etienne Audureau, Dominique Thabut, Angela Sutton, Fabien Zoulim, Laurent Alric, Carole Cagnot, Christine Silvain, Armand Abergel, Richard Layese, Fabrice Carrat, Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), ANRS France Recherche Nord & sud Sida-hiv hépatites, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Institut Arnault Tzanck, Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Hôpital Michallon, Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Agence Nationale de Recherches sur le Sida et les Hépatites Virales, Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées
Subjects: 0301 basic medicine, Cirrhosis, [SDV]Life Sciences [q-bio], Machine learning, computer.software_genre, HCV clearance, 03 medical and health sciences, 0302 clinical medicine, medicine, ComputingMilieux_MISCELLANEOUS, Prothrombin time, Hepatology, medicine.diagnostic_test, business.industry, Incidence (epidemiology), Cancer, medicine.disease, digestive system diseases, 3. Good health, 030104 developmental biology, Hepatocellular carcinoma, Cohort, Screening, 030211 gastroenterology & hepatology, Artificial intelligence, Liver cancer, business, Risk assessment, computer
Abstract: Background & Aims Refining hepatocellular carcinoma (HCC) surveillance programs requires improved individual risk prediction. Thus, we aimed to develop algorithms based on machine learning approaches to predict the risk of HCC more accurately in patients with HCV-related cirrhosis, according to their virological status. Methods Patients with compensated biopsy-proven HCV-related cirrhosis from the French ANRS CO12 CirVir cohort were included in a semi-annual HCC surveillance program. Three prognostic models for HCC occurrence were built, using (i) Fine-Gray regression as a benchmark, (ii) single decision tree (DT), and (iii) random survival forest for competing risks survival (RSF). Model performance was evaluated from C-indexes validated externally in the ANRS CO22 Hepather cohort (n = 668 enrolled between 08/2012–01/2014). Results Out of 836 patients analyzed, 156 (19%) developed HCC and 434 (52%) achieved sustained virological response (SVR) (median follow-up 63 months). Fine-Gray regression models identified 6 independent predictors of HCC occurrence in patients before SVR (past excessive alcohol intake, genotype 1, elevated AFP and GGT, low platelet count and albuminemia) and 3 in patients after SVR (elevated AST, low platelet count and shorter prothrombin time). DT analysis confirmed these associations but revealed more complex interactions, yielding 8 patient groups with varying cancer risks and predictors depending on SVR achievement. On RSF analysis, the most important predictors of HCC varied by SVR status (non-SVR: platelet count, GGT, AFP and albuminemia; SVR: prothrombin time, ALT, age and platelet count). Externally validated C-indexes before/after SVR were 0.64/0.64 [Fine-Gray], 0.60/62 [DT] and 0.71/0.70 [RSF]. Conclusions Risk factors for hepatocarcinogenesis differ according to SVR status. Machine learning algorithms can refine HCC risk assessment by revealing complex interactions between cancer predictors. Such approaches could be used to develop more cost-effective tailored surveillance programs. Lay summary Patients with HCV-related cirrhosis must be included in liver cancer surveillance programs, which rely on ultrasound examination every 6 months. Hepatocellular carcinoma (HCC) screening is hampered by sensitivity issues, leading to late cancer diagnoses in a substantial number of patients. Refining surveillance periodicity and modality using more sophisticated imaging techniques such as MRI may only be cost-effective in patients with the highest HCC incidence. Herein, we demonstrate how machine learning algorithms (i.e. data-driven mathematical models to make predictions or decisions), can refine individualized risk prediction.
Published: 2020
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33. Management of primary biliary cholangitis: results from a large real-life observational study in France and Belgium

Author: and Descript, Armand Garioud, Study Groups, Jean-Pierre Arpurt, Descript, Jean Henrion, Olivier Chazouillères, Christophe Corpechot, Alexandre Pariente, Christophe Renou, Isabelle Rosa, Xavier Causse, and Bertrand Hanslik
Subjects: Male, medicine.medical_specialty, Cholagogues and Choleretics, Cirrhosis, Disease, Gastroenterology, Belgium, Internal medicine, Albumins, medicine, Humans, Stage (cooking), Retrospective Studies, Hepatology, medicine.diagnostic_test, business.industry, Liver Cirrhosis, Biliary, Ursodeoxycholic Acid, Retrospective cohort study, Bilirubin, Middle Aged, medicine.disease, Ursodeoxycholic acid, Liver biopsy, Portal hypertension, Female, France, Transient elastography, business, medicine.drug
Abstract: BACKGROUND AND AIMS To assess the characteristics, care, treatment response, and outcomes of primary biliary cholangitis (PBC) patients recently followed-up by hepato-gastroenterologists in various French and Belgian healthcare settings. METHODS This retrospective cohort study included patients with PBC who recently visited 79 hepato-gastroenterologists in France and Belgium. Data were collected at the time of diagnosis and at last visit and were compared according to biochemical response (BR) to ursodeoxycholic acid (UDCA) (BR), using Paris I-II criteria, and clinical outcomes. RESULTS A total of 436 patients (mean age at diagnosis 57 years, 88% females, median follow-up 5.2 years) were included. Liver biopsy, transient elastography, or none of these two procedures were performed at baseline in 216 (50%), 194 (45%), and 107 (25%) patients, respectively. Late-stage disease (histological stage III or IV, or transient elastography ≥9.6 kPa, or bilirubin >17 µM and albumin
Published: 2020

34. Risk factors of de novo malignancies after liver transplantation: a French national study on 11004 adult patients

Author: Christophe Duvoux, Mario Altieri, Nassim Kamar, Jean Gugenheim, Sébastien Dharancy, Filomena Conti, Armand Abergel, Olivier Sérée, Georges-Philippe Pageaux, Ephrem Salamé, Jean Hardwigsen, Karim Boudjema, Pascal Lebray, Philippe Segol, Camille Besch, Vincent Leroy, Didier Samuel, Guy Launoy, Claire Vanlemmens, Sylvie Radenne, Maryline Debette-Gratien, Olivier Chazouillères, Xavier Blaizot, Martine Neau-Cransac, Claire Francoz, Marianne Latournerie, Jérôme Dumortier, Audrey Coilly, Pauline Houssel-Debry, François Durand, Olivier Boillot, Faouzi Saliba, Thierry Lobbedez, CCSD, Accord Elsevier, Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, CHU Pontchaillou [Rennes], Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Centre de Référence des Maladies Rares - Maladies Inflammatoires des Voies Biliaires et Service d’Hépatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Henri Mondor, Ecole Polytechnice Universitaire de Nice (EPU Nice -Polytech'Nice-Sophia), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Néphrologie - Immunologie Clinique [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-PRES Université de Toulouse, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hospices Civils de Lyon (HCL), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), and CHU Strasbourg
Subjects: Oncology, Adult, Male, medicine.medical_specialty, MESH: Liver Transplantation, Liver tumor, medicine.medical_treatment, Liver transplantation, Malignancy, Primary sclerosing cholangitis, 03 medical and health sciences, Liver disease, 0302 clinical medicine, MESH: Liver Neoplasms, MESH: Risk Factors, Risk Factors, Internal medicine, medicine, Humans, MESH: Incidence, Lung cancer, Retrospective Studies, MESH: Humans, Hepatology, business.industry, Incidence, Liver Neoplasms, Gastroenterology, Retrospective cohort study, MESH: Adult, MESH: Retrospective Studies, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Competing risk, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Male, Liver Transplantation, 030220 oncology & carcinogenesis, Population study, 030211 gastroenterology & hepatology, business, Liver transplantationde novomalignancies
Abstract: International audience; Background: After liver transplantation (LT),de novo malignancies are one of the leading causes of late mortality. The aim of the present retrospective study was to identify the risk factors of de novo malignancies in a large cohort of LT recipients in France, using Fine and Gray competing risks regression analysis.Methods: The study population consisted in 11004 adults transplanted between 2000 and 2013, who had no history of pre-transplant malignancy, except primary liver tumor. A Cox model adapted to the identification of prognostic factors (competitive risks) was used.Results: From the entire cohort, one (or more)de novo malignancy was reported in 1480 L T recipients (13.45%). The probability to develop a de novo malignancy after LT was 2.07% at 1 year, 13.30% at 5 years, and 28.01% at 10 years. Of the known reported malignancies, the most common malignancies were hematological malignancy (22.36%), non-melanoma skin cancer (19.53%) and lung cancer (12.36%). According to Fine and Gray competing risks regression multivariate analysis, were significant risk factors for post-LT de novo malignancy: recipient age (Subdistribution Hazard Ratio (SHR) = 1.03 95%CI 1.03-1.04), male gender (SHR = 1.45 95%CI 1.27-1.67), non-living donor (SHR = 1.67 95%CI 1.14-2.38), a first LT (SHR = 1.35 95%CI 1.09-1.69) and the type of initial liver disease (alcohol-related liver disease (SHR = 1.63 95%CI 1.22-2.17), primary sclerosing cholangitis (SHR = 1.98 95%CI 1.34-2.91), and primary liver tumor (SHR = 1.88 95%CI 1.41-2.54)). Initial immunosuppressive regimen had no significant impact.Conclusion: The present study confirms that LT recipient characteristics are associated with the risk ofde novo malignancy and this underlines the need for personalized screening in order to improve survival.
Published: 2020
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35. Origin, HDV genotype and persistent viremia determine outcome and treatment response in patients with chronic hepatitis delta

Author: Isabelle Rosa, Fabien Zoulim, Vincent Thibault, Christophe Hézode, Victor de Ledinghen, Thierry Poynard, Xavier Causse, Sophie Hillaire, Hélène Fontaine, Richard Layese, Jérôme Gournay, Nathalie Ganne, Ghassan Riachi, Emmanuel Gordien, Eric Nguyen-Khac, Sophie Metivier, Olivier Chazouillères, Dominique Roulot, Roland Landman, Paul Calès, Dominique Salmon, Pierre Nahon, Cécile Goujard, Zahia Ben-Abdesselam, Ségolène Brichler, H. Labadie, Jean-François Cadranel, Caroline Lascoux-Combe, Véronique Loustaud-Ratti, Bruno Roche, P. Sellier, Corinne Castelnau, Frédéric Le Gal, Philippe Mathurin, Dominique Guyader, Julie Bottero, Françoise Roudot-Thoraval, Laurent Alric, François Habersetzer, Caroline Scholtes, Jean-Didier Grangé, Sylvie Naveau, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hospices Civils de Lyon (HCL), Hôpital Paul Brousse, Hôpital Beaujon [AP-HP], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Jean Verdier [AP-HP], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Pontchaillou [Rennes], Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Agence Nationale de Recherches sur le Sida et les Hépatites Virales, France REcherche Nord & sud Sida-HIV Hépatites, Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Jonchère, Laurent
Subjects: Adult, Liver Cirrhosis, Male, 0301 basic medicine, medicine.medical_specialty, Carcinoma, Hepatocellular, Cirrhosis, Hepatitis D, Chronic, viruses, African origin, HDV persistent viremia, [SDV]Life Sciences [q-bio], Chronic liver disease, Severity of Illness Index, HDV genotype, 03 medical and health sciences, 0302 clinical medicine, Residence Characteristics, Internal medicine, medicine, Humans, Decompensation, Viremia, Retrospective Studies, Deltavir study, Liver infection, Hepatology, business.industry, Liver Neoplasms, virus diseases, Retrospective cohort study, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Viral Load, biochemical phenomena, metabolism, and nutrition, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Cohort, Female, 030211 gastroenterology & hepatology, France, Interferons, Hepatitis Delta Virus, Viral hepatitis, business, Viral load, Liver outcome
Abstract: International audience; Background & aims: HDV infection causes severe chronic liver disease in individuals infected with HBV. However, the factors associated with poor prognosis are largely unknown. Thus, we aimed to identify prognostic factors in patients with HDV infection.Methods: The French National Reference Centre for HDV performed a nationwide retrospective study on 1,112 HDV-infected patients, collecting epidemiological, clinical, virological and histological data from the initial referral to the last recorded follow-up.Results: The median age of our cohort was 36.5 (29.9-43.2) years and 68.6% of our cohort were male. Most patients whose birthplace was known were immigrants from sub-Saharan Africa (52.5%), southern and eastern Europe (21.3%), northern Africa and the Middle East (6.2%), Asia (5.9%) and South America (0.3%). Only 150 patients (13.8%) were French native. HDV load was positive in 659 of 748 tested patients (88.1%). HDV-1 was predominant (75.9%), followed by sub-Saharan genotypes: HDV-5 (17.6%), HDV-7 (2.9%), HDV-6 (1.8%) and HDV-8 (1.6%). At referral, 312 patients (28.2%) had cirrhosis, half having experienced at least 1 episode of hepatic decompensation. Cirrhosis was significantly less frequent in African than in European patients regardless of HDV genotype. At the end of follow-up (median 3.0 [0.8-7.2] years), 48.8% of the patients had developed cirrhosis, 24.2% had ≥1 episode(s) of decompensation and 9.2% had hepatocellular carcinoma. European HDV-1 and African HDV-5 patients were more at risk of developing cirrhosis. Persistent replicative HDV infection was associated with decompensation, hepatocellular carcinoma and death. African patients displayed better response to interferon therapy than non-African patients (46.4% vs. 29.1%, p
Published: 2020
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36. Primary Biliary Cholangitis: Autoimmune Hepatitis Overlap Syndrome

Author: Nora Cazzagon and Olivier Chazouillères
Subjects: Autoimmune disease, Immunosuppressive treatment, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Autoantibody, Overlap syndrome, Autoimmune hepatitis, medicine.disease, Gastroenterology, digestive system diseases, Ursodeoxycholic acid, Serology, Internal medicine, Liver biopsy, Medicine, business, medicine.drug
Abstract: Overlap syndromes (OSs) between primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) represent rare forms of PBC and AIH. The diagnosis of OS is based on the presence or sequential development of biochemical, serological, and histologic features of the two diseases. Liver biopsy is mandatory when PBC-AIH OS is suspected and moderate or interface hepatitis is a fundamental component for the diagnosis of OS. OS should not be over-diagnosed, and it is generally recommended to use the Paris diagnostic criteria. Patients may present with one or more associated extra-hepatic autoimmune disease. PBC-AIH OS seems to have a more severe presentation and course compared to conventional PBC. Treatment of OS is empiric and includes ursodeoxycholic acid (UDCA) for the cholestatic component and immunosuppressive agents for the hepatitic component. Immunosuppressive treatment in addition to UDCA is recommended in patients with severe interface hepatitis. In those with moderate interface hepatitis, the dominant clinical feature should be treated first and therapy adjusted according to the response.
Published: 2020
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37. Sofosbuvir-Daclatasvir Is Suboptimal in Patients with Genotype 2 Chronic Hepatitis C Infection: Real-life Experience from the HEPATHER ANRS CO22 Cohort

Author: Dominique Larrey, Albert Tran, Fabrice Carrat, Didier Samuel, Stéphane Chevaliez, Fabien Zoulim, Hélène Fontaine, Jean-Michel Pawlotsky, Olivier Chazouillères, Jean-Pierre Bronowicki, Céline Dorival, Afef, Patrick Marcellin, Clovis Lusivika-Nzinga, Stanislas Pol, Victor de Ledinghen, Sophie Metivier, Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Hépatologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), CHU Toulouse [Toulouse], Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Service de Chirurgie Digestive / Centre de Transplantation Hépatique [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de Référence Virus des hépatites B, C et Delta, Institut National de la Transfusion Sanguine [Paris] (INTS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], CHU Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Gestionnaire, Hal Sorbonne Université
Subjects: medicine.medical_specialty, Pyrrolidines, Daclatasvir, Genotype, Sofosbuvir, [SDV]Life Sciences [q-bio], Hepacivirus, Antiviral Agents, chemistry.chemical_compound, Virology, Internal medicine, medicine, Humans, Prospective Studies, Adverse effect, Hepatitis, Hepatology, business.industry, Ribavirin, Imidazoles, virus diseases, Valine, Hepatitis C, Hepatitis C, Chronic, medicine.disease, digestive system diseases, Discontinuation, [SDV] Life Sciences [q-bio], Regimen, Infectious Diseases, chemistry, Drug Therapy, Combination, Carbamates, business, medicine.drug
Abstract: Sofosbuvir plus daclatasvir with or without ribavirin has demonstrated a high efficacy and an acceptable safety profile in clinical trials of patients infected with genotype 2 hepatitis Cvirus (HCV); however, there are currently no real-world data available for this regimen. To evaluate the real-life safety and efficacy of sofosbuvir/daclatasvir with or without ribavirin in genotype 2 HCV patients in the French cohort ANRS CO22 HEPATHER(NCT01953458). In this ongoing, national, multicentre, prospective, observational study, we observed patients with HCV genotype 2 infection who initiated treatment with sofosbuvir (400 mg/d) plus daclatasvir with or without ribavirin (1-1.2 g/d). Patients were divided into two treatment groups: sofosbuvir/daclatasvir with or without ribavirin (12 weeks/24 weeks). The primary end point was a sustained virological response at week 12 following the end of therapy. Overall, 88% and 91% of patients achieved a sustained virological response following 12 and 24 weeks of treatment with sofosbuvir/daclatasvir with or without ribavirin, respectively. The most common adverse events were asthenia (29%), headache (15%) and fatigue (20%), and ribavirin addition was associated with a higher rate of adverse events and treatment discontinuation. Sofosbuvir/daclatasvir with or without ribavirin was associated with lower rates of sustained virological response in the real-life setting compared with the clinical setting and demonstrated suboptimal efficacy for the treatment of patients with genotype 2 chronic HCV.
Published: 2020
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38. Early hepatocellular carcinoma detection using magnetic resonance imaging is cost-effective in high-risk patients with cirrhosis

Author: Pierre Nahon, Marie Najean, Richard Layese, Kevin Zarca, Laeticia Blampain Segar, Carole Cagnot, Nathalie Ganne-Carrié, Gisèle N’Kontchou, Stanislas Pol, Cendrine Chaffaut, Fabrice Carrat, Maxime Ronot, Etienne Audureau, Isabelle Durand-Zaleski, Tarik Asselah, Dominique Guyader, Hélène Fontaine, Georges-Philippe Pageaux, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Dominique Roulot, Albert Tran, Jean-Pierre Bronowicki, Thomas Decaensi, Ghassan Riachi, Paul Calès, Jean-Marie Péron, Laurent Alric, Marc Bourlière, Philippe Mathurin, Sebastien Dharancy, Jean-Frédéric Blanc, Armand Abergel, Olivier Chazouillères, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, Louis d’Alteroche, Claire Wartelle, Thông Dao, Dominique Thabut, Christophe Pilette, Christine Silvain, Christos Christidis, Eric Nguyen-Khac, Brigitte Bernard-Chabert, Sophie Hillaire, Vincent Di Martino, Delphine Bonnet, Virginie Payssan-Sicart, Chloe Pomes, François Bailly, Marjolaine Beaudoin, Dominique Giboz, Kerstin Hartig-Lavie, Marianne Maynard, Eric Billaud, David Boutoille, Morane Cavellec, Marjorie Cheraud-Carpentier, Isabelle Hubert, Jaouad Benhida, Adrien Lannes, Françoise Lunel, Frédéric Oberti, Nathalie Boyer, Nathalie Giuily, Corinne Castelnau, Giovanna Scoazec, Aziza Chibah, Sylvie Keser, Karim Bonardi, Anaïs Vallet-Pichard, Philippe Sogni, Juliette Foucher, Jean-Baptiste Hiriart, Amy Wilson, Sarah Shili, Faiza Chermak, Christelle Ansaldi, Nisserine Ben Amara, Laëtitia Chouquet, Emilie De Luca, Valérie Oules, Rodolphe Anty, Eve Gelsi, Régine Truchi, Elena Luckina, Nadia Messaoudi, Joseph Moussali, Barbara De Dieuleveult, Damien Labarriere, Pascal Poter, Si Nafa Si Ahmed, Véronique Grando-Lemaire, Valérie Bourcier, Séverine Brulé, Thomas Stalhberger, Caroline Jezequel, Audrey Brener, Anne Laligant, Aline Rabot, Isabelle Renard, Thomas F. Baumert, Michel Dofföel, Catherine Mutter, Pauline Simo-Noumbissie, Esma Razi, Hélène Barraud, Mouni Bensenane, Abdelbasset Nani, Sarah Hassani-Nani, Marie-Albertine Bernard, Michael Bismuth, Ludovic Caillo, Stéphanie Faure, Marie Pierre Ripault, Christophe Bureau, Jean Marie Peron, Marie Angèle Robic, Léa Tarallo, Marine Faure, Bruno Froissart, Marie-Noelle Hilleret, Jean-Pierre Zarski, Odile Goria, Victorien Grard, Hélène Montialoux, Muriel François, Christian Ouedraogo, Christelle Pauleau, Anne Varault, Tony Andreani, Bénédicte Angoulevant, Azeline Chevance, Lawrence Serfaty, Teresa Antonini, Audrey Coilly, Jean-Charles Duclos Vallée, Mariagrazia Tateo, Corinne Bonny, Chanteranne Brigitte, Géraldine Lamblin, Léon Muti, Abdenour Babouri, Virginie Filipe, Camille Barrault, Laurent Costes, Hervé Hagège, Soraya Merbah, Paul Carrier, Maryline Debette-Gratien, Jérémie Jacques, Guillaume Lassailly, Florent Artu, Valérie Canva, Sébastien Dharancy, Alexandre Louvet, Marianne Latournerie, Marc Bardou, Thomas Mouillot, Yannick Bacq, Didier Barbereau, Charlotte Nicolas, Caroline Chevalier, Isabelle Archambeaud, Sarah Habes, Danièle Botta-Fridlund, Eric Saillard, Marie-Josée Lafrance, Patrice Cacoub, Patrizia Carrieri, Elisabeth Delarocque-Astagneau, Victor De Ledinghen, Céline Dorival, Jean Dubuisson, Chantal Housset, Dominique Larrey, Patrick Marcellin, Jean-Michel Pawlotsky, Ventzislava Petrov-Sanchez, Sophie Vaux, Linda Wittkop, Yazdan Yazdanpanah, Jessica Zucman-Rossi, Christophe Moreno, Romain Moirand, Nicolas Carbonell, Jean-Charles Duclos-Vallée, Victor de Ledinghen, Violaine Ozenne, Jean Henrion, Gabriel Perlemuter, Xavier Amiot, Sylvie Chevret, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13), Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] (FunGeST), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Henri Mondor, Unité de recherche clinique en économie de la santé [Paris] (URC Eco), Délégation de la Recherche Clinique et de l’Innovation [Paris] (DRCI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), ANRS|Maladies infectieuses émergentes (ANRS|MIE), Université Sorbonne Paris Nord, Hôpital Cochin [AP-HP], Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de santé publique [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Hôpital Beaujon [AP-HP]
Subjects: AMRI, abbreviated magnetic resonance imaging, NAFLD, non-alcoholic fatty liver disease, medicine.medical_specialty, Cirrhosis, Cost effectiveness, [SDV]Life Sciences [q-bio], Population, TACE, transarterial chemoembolization, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Gastroenterology, QALY, quality-adjusted life year, Internal medicine, Internal Medicine, LY, life years, Immunology and Allergy, Medicine, Early Hepatocellular Carcinoma, liver cancer risk, education, cost-effectiveness, RFA, radiofrequency ablation, education.field_of_study, AFP, alpha-fetoprotein, US, ultrasound, Hepatology, medicine.diagnostic_test, business.industry, cirrhosis, LYG, life years gained, Incidence (epidemiology), BCLC, Barcelona Clinic Liver Cancer, ICER, incremental cost-effectiveness ratio, Magnetic resonance imaging, medicine.disease, HR, hazard ratio, digestive system diseases, Hepatocellular carcinoma, SHR, subdistribution hazard ratio, surveillance, HCC, hepatocellular carcinoma, business, MRI, magnetic resonance imaging, Incremental cost-effectiveness ratio, Research Article, MRI
Abstract: Background & Aims Reinforced hepatocellular carcinoma (HCC) surveillance using magnetic resonance imaging (MRI) could increase early tumour detection but faces cost-effectiveness issues. In this study, we aimed to evaluate the cost-effectiveness of MRI for the detection of very early HCC (Barcelona Clinic Liver Cancer [BCLC] 0) in patients with an annual HCC risk >3%. Methods French patients with compensated cirrhosis included in 4 multicentre prospective cohorts were considered. A scoring system was constructed to identify patients with an annual risk >3%. Using a Markov model, the economic evaluation estimated the costs and life years (LYs) gained with MRI vs. ultrasound (US) monitoring over a 20-year period. The incremental cost-effectiveness ratio (ICER) was calculated by dividing the incremental costs by the incremental LYs. Results Among 2,513 patients with non-viral causes of cirrhosis (n = 840) and/or cured HCV (n = 1,489)/controlled HBV infection (n = 184), 206 cases of HCC were detected after a 37-month follow-up. When applied to training (n = 1,658) and validation (n = 855) sets, the construction of a scoring system identified 33.4% and 37.5% of patients with an annual HCC risk >3% (3-year C-Indexes 75 and 76, respectively). In patients with a 3% annual risk, the incremental LY gained with MRI was 0.4 for an additional cost of €6,134, resulting in an ICER of €15,447 per LY. Compared to US monitoring, MRI detected 5x more BCLC 0 HCC. The deterministic sensitivity analysis confirmed the impact of HCC incidence. At a willingness to pay of €50,000/LY, MRI screening had a 100% probability of being cost-effective. Conclusions In the era of HCV eradication/HBV control, patients with annual HCC risk >3% represent one-third of French patients with cirrhosis. MRI is cost-effective in this population and could favour early HCC detection. Lay summary The early identification of hepatocellular carcinoma in patients with cirrhosis is important to improve patient outcomes. Magnetic resonance imaging could increase early tumour detection but is more expensive and less accessible than ultrasound (the standard modality for surveillance). Herein, using a simple score, we identified a subgroup of patients with cirrhosis (accounting for >one-third), who were at increased risk of hepatocellular carcinoma and for whom the increased expense of magnetic resonance imaging would be justified by the potential improvement in outcomes., Graphical abstract, Highlights • HCC risk stratification in patients with cirrhosis aims at improving performance of cancer surveillance. • Using a simple scoring system, one-third of patients with cirrhosis with an annual HCC risk >3% can be easily identified. • Semi-annual surveillance using MRI in this population could enable the cost-effective detection of 5x more BCLC 0 HCCs.
Published: 2022
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39. Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis

Author: Martina Sterneck, Wolfgang Lieb, Christian Rust, Tom H. Karlsen, Massimo Pinzani, Erik Schrumpf, John E. Eaton, Gideon M. Hirschfield, Christoph Schramm, Richard Sandford, Ulrich Beuers, Andrew Mason, Espen Melum, Daniel Gotthardt, A. Boudewijn de Vries, I. Franceschet, Konstantinos N. Lazaridis, Floris Imhann, Marco Carbone, Pietro Invernizzi, Mark S. Silverberg, Simon Hohenester, Maria Consiglia Bragazzi, Andreas Teufel, Bart van Hoek, Martti Färkkilä, Einar Bjornsson, Cyriel Y. Ponsioen, Brijesh Srivastava, Joanne Verheij, Roger W. Chapman, Krista Rombouts, Niklas K. Björkström, Johannes R. Hov, Weiwei Wang, F. Sampaziotis, Ludovic Vallier, Albert Parés, Eleonora A. M. Festen, Kristian Holm, Kalliopi Zachou, Katrin Böttcher, Christopher L. Bowlus, Xiaojun Jiang, Trine Folseraas, Elisabeth M.G. de Vries, Simon M. Rushbrook, Piotr Milkiewicz, Carl A. Anderson, Georgios N. Dalekos, David Ellinghaus, Hanns-Ulrich Marschall, Rinse K. Weersma, Marco Marzioni, Olivier Chazouillères, Domenico Alvaro, Christian Rupp, Angela M. Cheung, Jimmy Z. Liu, Brian D. Juran, Michael P. Manns, Rudi Alberts, Bertus Eksteen, Tobias J. Weismüller, Graeme J.M. Alexander, Annarosa Floreani, Tobias Müller, Stefan Schreiber, Andre Franke, Elizabeth C. Goode, Henrike Lenzen, Arnau Vich Vila, Annika Bergquist, Kirsten Muri Boberg, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Gastroenterology and Hepatology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Graduate School, Pathology, Alberts, R, De Vries, E, Goode, E, Jiang, X, Sampaziotis, F, Rombouts, K, Böttcher, K, Folseraas, T, Weismüller, T, Mason, A, Wang, W, Alexander, G, Alvaro, D, Bergquist, A, Björkström, N, Beuers, U, Björnsson, E, Boberg, K, Bowlus, C, Bragazzi, M, Carbone, M, Chazouillères, O, Cheung, A, Dalekos, G, Eaton, J, Eksteen, B, Ellinghaus, D, Färkkilä, M, Festen, E, Floreani, A, Franceschet, I, Gotthardt, D, Hirschfield, G, Hoek, B, Holm, K, Hohenester, S, Hov, J, Imhann, F, Invernizzi, P, Juran, B, Lenzen, H, Lieb, W, Liu, J, Marschall, H, Marzioni, M, Melum, E, Milkiewicz, P, Müller, T, Pares, A, Rupp, C, Rust, C, Sandford, R, Schramm, C, Schreiber, S, Schrumpf, E, Silverberg, M, Srivastava, B, Sterneck, M, Teufel, A, Vallier, L, Verheij, J, Vila, A, Vries, B, Zachou, K, Chapman, R, Manns, M, Pinzani, M, Rushbrook, S, Lazaridis, K, Franke, A, Anderson, C, Karlsen, T, Ponsioen, C, Weersma, R, Centre of Excellence in Complex Disease Genetics, Doctoral Programme in Drug Research, Department of Medicine, Clinicum, Gastroenterologian yksikkö, HUS Abdominal Center, and Universitat de Barcelona
Subjects: Male, 0301 basic medicine, Oncology, Candidate gene, Cholangitis, medicine.medical_treatment, Medizin, Trasplantament hepàtic, Genome-wide association study, Kaplan-Meier Estimate, LIVER FIBROSIS, Liver transplantation, Bioinformatics, Sclerosing, Oral and gastrointestinal, Primary sclerosing cholangitis, genetics, liver transplantation, Cohort Studies, ACTIVATION, 0302 clinical medicine, MED/12 - GASTROENTEROLOGIA, MULTIPLE, 2.1 Biological and endogenous factors, EPIDEMIOLOGY, Aetiology, CIRRHOSIS, Bilious diseases and biliousness, Liver Disease, digestive, oral, and skin physiology, Gastroenterology, Single Nucleotide, Primary sclerosing cholangiti, Middle Aged, 3. Good health, ULCERATIVE-COLITIS, Disease Progression, Female, 030211 gastroenterology & hepatology, Adult, medicine.medical_specialty, Cholangitis, Sclerosing, Chronic Liver Disease and Cirrhosis, Clinical Sciences, Malalties del tracte biliar, Single-nucleotide polymorphism, HEPATIC STELLATE CELLS, Polymorphism, Single Nucleotide, International PSC Study Group, Article, Paediatrics and Reproductive Medicine, 03 medical and health sciences, Rare Diseases, Clinical Research, Internal medicine, Genetics, medicine, Humans, Polymorphism, GENOME-WIDE ASSOCIATION, Allele, Digestive Diseases - (Gallbladder), Survival analysis, Proportional Hazards Models, MALIGNANCY, The UK PSC Consortium, Transplantation, Gastroenterology & Hepatology, business.industry, Proportional hazards model, medicine.disease, RISK LOCI, Logistic Models, 030104 developmental biology, 3121 General medicine, internal medicine and other clinical medicine, genetic, Hepatic transplantation, Thrombospondins, Digestive Diseases, business, Genètica
Abstract: ObjectivePrimary sclerosing cholangitis (PSC) is a genetically complex, inflammatory bile duct disease of largely unknown aetiology often leading to liver transplantation or death. Little is known about the genetic contribution to the severity and progression of PSC. The aim of this study is to identify genetic variants associated with PSC disease progression and development of complications.DesignWe collected standardised PSC subphenotypes in a large cohort of 3402 patients with PSC. After quality control, we combined 130 422 single nucleotide polymorphisms of all patients—obtained using the Illumina immunochip—with their disease subphenotypes. Using logistic regression and Cox proportional hazards models, we identified genetic variants associated with binary and time-to-event PSC subphenotypes.ResultsWe identified genetic variant rs853974 to be associated with liver transplant-free survival (p=6.07×10–9). Kaplan-Meier survival analysis showed a 50.9% (95% CI 41.5% to 59.5%) transplant-free survival for homozygous AA allele carriers of rs853974 compared with 72.8% (95% CI 69.6% to 75.7%) for GG carriers at 10 years after PSC diagnosis. For the candidate gene in the region, RSPO3, we demonstrated expression in key liver-resident effector cells, such as human and murine cholangiocytes and human hepatic stellate cells.ConclusionWe present a large international PSC cohort, and report genetic loci associated with PSC disease progression. For liver transplant-free survival, we identified a genome-wide significant signal and demonstrated expression of the candidate gene RSPO3 in key liver-resident effector cells. This warrants further assessments of the role of this potential key PSC modifier gene.
Published: 2017
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40. HLA haplotypes in primary sclerosing cholangitis patients of admixed and non-European ancestry

Author: Johannes R. Hov, Stuart C. Gordon, Kidist K. Yimam, Konstantinos N. Lazaridis, Brian D. Juran, Trine Folseraas, Marte K. Viken, B. Eksteen, L. Yu, Eva Kristine Klemsdal Henriksen, Rinse K. Weersma, Christopher L. Bowlus, Daniel Gotthardt, Michael Wittig, Espen Melum, Simon M. Rushbrook, E. Goode, Sören Mucha, Olivier Chazouillères, Benedicte A. Lie, Tom H. Karlsen, Kristian Holm, Cyriel Y. Ponsioen, David S. Goldberg, Pietro Invernizzi, Andre Franke, Martti Färkkilä, Gideon M. Hirschfield, and Marco Carbone
Subjects: 0301 basic medicine, Genetics, education.field_of_study, Linkage disequilibrium, endocrine system diseases, Immunology, Population, Haplotype, Human leukocyte antigen, Biology, medicine.disease, Primary sclerosing cholangitis, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, immune system diseases, medicine, Immunology and Allergy, Chronic Cholangitis, education, Allele frequency, 030217 neurology & neurosurgery, HLA Complex
Abstract: Primary sclerosing cholangitis (PSC) is strongly associated with several human leukocyte antigen (HLA) haplotypes. Due to extensive linkage disequilibrium and multiple polymorphic candidate genes in the HLA complex, identifying the alleles responsible for these associations has proven difficult. We aimed to evaluate whether studying populations of admixed or non-European descent could help in defining the causative HLA alleles. When assessing haplotypes carrying HLA-DRB1*13:01 (hypothesized to specifically increase the susceptibility to chronic cholangitis), we observed that every haplotype in the Scandinavian PSC population carried HLA-DQB1*06:03. In contrast, only 65% of HLA-DRB1*13:01 haplotypes in an admixed/non-European PSC population carried this allele, suggesting that further assessments of the PSC-associated haplotype HLA-DRB1*13:01-DQA1*01:03-DQB1*06:03 in admixed or multi-ethnic populations could aid in identifying the causative allele.
Published: 2017
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41. Biologie des maladies cholestatiques chroniques de l’adulte

Author: Sara Lemoinne and Olivier Chazouillères
Subjects: Medical Laboratory Technology, Biochemistry (medical), Analytical Chemistry
Abstract: Resume La cholestase est definie par un defaut de transport des acides biliaires du foie vers l’intestin. Les tests de cholestase refletent d’une part les lesions des hepatocytes ou des cellules epitheliales biliaires induites par l’accumulation des acides biliaires (enzymes hepatiques) et d’autre part les alterations fonctionnelles de la secretion biliaire (bilirubine, acides biliaires). La ponction biopsie hepatique garde une place dans le diagnostic etiologique d’une cholestase chronique. Les principales maladies cholestatiques chroniques de l’adulte sont la cholangite biliaire primitive (CBP) et la cholangite sclerosante primitive (CSP). Des facteurs pronostiques ont ete identifies. La mesure de la souplesse du foie par elastometrie semble un examen tres prometteur dans la prise en charge de ces maladies. Le traitement medical est base sur l’acide ursodesoxycholique. Cependant, de nouveaux agents anti-cholestatiques, en particulier les agonistes des recepteurs nucleaires, dont l’acide obeticholique et les fibrates, ont fait l’objet d’une evaluation preclinique et clinique prometteuse. Une amelioration de la prise en charge est donc hautement probable a court terme.
Published: 2017
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42. Individual patient data meta-analysis on controlled attenuation parameter for the XL probe in obese patients

Author: David Petroff, Valentin Blank, Shalimar Shalimar, Philip N Newsome, Cosmin Sebastian Voican, Maja Thiele, Victor de Lédinghen, Stephan Baumeler, Wah-Kheong Chan, Gabriel Perlemuter, Ana Carolina Cardoso, Sandeep Aggarwal, Magali Sasso, Peter Eddowes, Michael Allison, Emmanuel Tsochatzis, Quentin Anstee, David Sheridan, Jeremy Cobbold, Naveau Sylvie, Monica Lupsor-Platon, Sebastian Mueller, Aleksander Krag, Marie Irles-Depe, David Semela, Grace Lai-Hung Wong, Vincent Wai-Sun Wong, Cristiane Villela-Nogueira, Garg Harshit, Olivier Chazouillères, Johannes Wiegand, and Thomas Karlas
Subjects: Hepatology
Published: 2020
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43. Letter: reduction in projected mortality or need for liver transplantation associated with bezafibrate add-on in primary biliary cholangitis with incomplete UDCA response

Author: Christophe Corpechot, Sara Lemoinne, Alexandra Rousseau, and Olivier Chazouillères
Subjects: medicine.medical_specialty, Cholangitis, medicine.medical_treatment, Liver transplantation, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Fenofibrate, Internal medicine, medicine, Humans, Pharmacology (medical), Reduction (orthopedic surgery), Bezafibrate, Hepatology, Liver Cirrhosis, Biliary, business.industry, Ursodeoxycholic Acid, Ursodeoxycholic acid, Liver Transplantation, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, business, medicine.drug
Published: 2018
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44. Switching vs. add-on strategy in PBC treatment: Lessons from UDCA and bezafibrate experience

Author: Alexandra Rousseau, Christophe Corpechot, and Olivier Chazouillères
Subjects: medicine.medical_specialty, Cholagogues and Choleretics, Bezafibrate, Hepatology, business.industry, Liver Cirrhosis, Biliary, Ursodeoxycholic Acid, MEDLINE, Internal medicine, medicine, Humans, business, medicine.drug
Published: 2019

45. Simple Magnetic Resonance Scores Associate With Outcomes of Patients With Primary Sclerosing Cholangitis

Author: Nora Cazzagon, Gideon M. Hirschfield, Christophe Corpechot, Astrid Kemgang, Jeffrey Barkun, Annarosa Floreani, Sara Lemoinne, Alan N. Barkun, Raffaella Motta, Olivier Chazouillères, Lionel Arrivé, Sanaâ El Mouhadi, Anthony Dohan, Yves Chretien, Chantal Housset, Palak J. Trivedi, Benoit Gallix, Karima Ben Belkacem, Centre de Référence des Maladies Rares - Maladies Inflammatoires des Voies Biliaires et Service d’Hépatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Radiologie [CHU Saint-Antoine], University of Birmingham [Birmingham], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hépatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], University Health Network, Department of Surgery, Oncology and Gastroenterology [Padova], Azienda Ospedaliera di Padova, Division of Gastroenterology [Padova], Azienda Ospedaliera di Padova -Azienda Ospedaliera di Padova, McGill University Health Center [Montreal] (MUHC), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and CCSD, Accord Elsevier
Subjects: Male, Cirrhosis, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, medicine.medical_treatment, Liver transplantation, Gastroenterology, Imaging, 0302 clinical medicine, Biliary Tract, biliary tract, cholestatic liver disease, imaging, prognosis, radiology, Univariate analysis, Middle Aged, Prognosis, Magnetic Resonance Imaging, 3. Good health, Liver, Cholestatic Liver Disease, 030220 oncology & carcinogenesis, Cohort, Disease Progression, 030211 gastroenterology & hepatology, Female, Radiology, Cholangiography, Dilatation, Pathologic, Adult, medicine.medical_specialty, Cholangitis, Sclerosing, Primary sclerosing cholangitis, 03 medical and health sciences, Internal medicine, Hypertension, Portal, medicine, Humans, Decompensation, Proportional Hazards Models, Retrospective Studies, Hepatology, Proportional hazards model, business.industry, Retrospective cohort study, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Liver Transplantation, Bile Ducts, Intrahepatic, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Atrophy, business
Abstract: Background & Aims Primary sclerosing cholangitis (PSC) has a variable, often progressive, course. Magnetic resonance cholangiography (MRC) is used in the diagnosis of PSC. Magnetic resonance risk scoring systems, called Anali without and with gadolinium, are used to predict disease progression, determined by radiologic factors. We aimed to assess the prognostic value of Anali scores in patients with PSC and validate our findings in a separate cohort. Methods We performed a retrospective study of patients with large-duct PSC (internal cohort, 119 patients in France; external cohort, 119 patients in Canada, Italy, and the United Kingdom). All the first-available MRC results were reviewed by 2 radiologists and the Anali scores were calculated as follows: Anali without gadolinium = (1× dilatation of intrahepatic bile ducts) + (2× dysmorphy) + (1× portal hypertension); Anali with gadolinium = (1× dysmorphy) + (1× parenchymal enhancement heterogeneity). The primary end point was survival without liver transplantation or cirrhosis decompensation. The prognostic value of Anali scores was assessed by Cox regression modeling. Results During a total of 549 patient-years for the internal cohort and 497 patient-years for the external cohort, we recorded 2 and 8 liver transplantations, 4 and 3 liver-related deaths, and 26 and 25 cirrhosis decompensations, respectively. In the univariate analysis, factors associated with survival without liver transplantation or cirrhosis decompensation in the internal cohort were as follows: serum levels of bilirubin, aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transferase, alkaline phosphatase, albumin, and Anali scores. Anali scores without and with gadolinium identified patients' survival without liver transplantation or cirrhosis decompensation with a c-statistic of 0.89 (95% CI, 0.84–0.95) and 0.75 (95% CI, 0.64–0.87), respectively. Independent prognostic factors identified by multivariate analysis were Anali scores and bilirubinemia. The prognostic value of Anali scores was confirmed in the external cohort. Conclusions In internal and external cohorts, we found that Anali scores, determined from MRC, were associated with outcomes of patients with PSC. These scores might be used as prognostic factors.
Published: 2019
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46. A Brief Reflection on Continuous vs Binary Risk Indicators in Primary Biliary Cholangitis

Author: Olivier Chazouillères and Christophe Corpechot
Subjects: medicine.medical_specialty, Hepatology, business.industry, Cholangitis, Liver Cirrhosis, Biliary, Ursodeoxycholic Acid, Gastroenterology, Binary number, Risk indicators, Risk Factors, medicine, Humans, Medical physics, Longitudinal Studies, Reflection (computer graphics), business
Published: 2019

47. Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment a prospective cohort study

Author: Albert Tran, Victor de Ledinghen, Armand Abergel, Céline Dorival, Olivier Chazouillères, Louis d’Alteroche, Isabelle Rosa, Didier Samuel, Moana Gelu-Simeon, Laurent Alric, Vincent Leroy, Jérôme Gournay, François Habersetzer, Dominique Guyader, Stanislas Pol, Véronique Loustaud-Ratti, Ghassan Riachi, Jean-Pierre Bronowicki, Hélène Fontaine, Anne Minello, Christophe Hézode, Philippe Mathurin, Claire Geist, Nathalie Ganne, Mélanie Simony, Dominique Thabut, François Raffi, Xavier Causse, Patrick Marcellin, Sophie Metivier, Paul Calès, Isabelle Portal, Marc Bourlière, Dominique Larrey, Fabien Zoulim, Fabrice Carrat, Alpha Diallo, Georges Haour, Tarik Asselah, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'hépatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANRS France Recherche Nord & sud Sida-hiv hépatites, Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire de Nice (CHU Nice), Interactions Virus-Hôte et Maladies Hépatiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Virologie, Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Physiopathologie des Maladies Inflammatoires de l'Intestin, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Rouen, Normandie Université (NU), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Image Science for Interventional Techniques (ISIT), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Centre National de la Recherche Scientifique (CNRS), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional d'Orléans (CHRO), Service d'Hépato-gastro-entérologie [CHR Metz-Thionville], Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Equipe EPICAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Intercommunal de Créteil (CHIC), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Aix Marseille Université (AMU), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Toulouse [Toulouse], Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], CCSD, Accord Elsevier, Institut National de la Recherche Agronomique (INRA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Cirrhosis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Liver transplantation, Antiviral Agents, Gastroenterology, 03 medical and health sciences, Liver disease, Viewpoint, 0302 clinical medicine, Internal medicine, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Aged, Proportional Hazards Models, business.industry, Incidence, Liver Neoplasms, Hazard ratio, General Medicine, Hepatitis C, Hepatitis C, Chronic, Middle Aged, Hepatology, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Hepatocellular carcinoma, Female, France, business
Abstract: Although direct-acting antivirals have been used extensively to treat patients with chronic hepatitis C virus (HCV) infection, their clinical effectiveness has not been well reported. We compared the incidence of death, hepatocellular carcinoma, and decompensated cirrhosis between patients treated with direct-acting antivirals and those untreated, in the French ANRS CO22 Hepather cohort.We did a prospective study in adult patients with chronic HCV infection enrolled from 32 expert hepatology centres in France. We excluded patients with chronic hepatitis B, those with a history of decompensated cirrhosis, hepatocellular carcinoma, or liver transplantation, and patients who were treated with interferon-ribavirin with or without first-generation protease inhibitors. Co-primary study outcomes were incidence of all-cause mortality, hepatocellular carcinoma, and decompensated cirrhosis. The association between direct-acting antivirals and these outcomes was quantified using time-dependent Cox proportional hazards models. This study is registered with ClinicalTrials.gov, number NCT01953458.Between Aug 6, 2012, and Dec 31, 2015, 10 166 patients were eligible for the study. 9895 (97%) patients had available follow-up information and were included in analyses. Median follow-up was 33·4 months (IQR 24·0-40·7). Treatment with direct-acting antivirals was initiated during follow-up in 7344 patients, and 2551 patients remained untreated at the final follow-up visit. During follow-up, 218 patients died (129 treated, 89 untreated), 258 reported hepatocellular carcinoma (187 treated, 71 untreated), and 106 had decompensated cirrhosis (74 treated, 32 untreated). Exposure to direct-acting antivirals was associated with increased risk for hepatocellular carcinoma (unadjusted hazard ratio [HR] 2·77, 95% CI 2·07-3·71) and decompensated cirrhosis (3·83, 2·29-6·42). After adjustment for variables (age, sex, body-mass index, geographical origin, infection route, fibrosis score, HCV treatment-naive, HCV genotype, alcohol consumption, diabetes, arterial hypertension, biological variables, and model for end-stage liver disease score in patients with cirrhosis), exposure to direct-acting antivirals was associated with a decrease in all-cause mortality (adjusted HR 0·48, 95% CI 0·33-0·70) and hepatocellular carcinoma (0·66, 0·46-0·93), and was not associated with decompensated cirrhosis (1·14, 0·57-2·27).Treatment with direct-acting antivirals is associated with reduced risk for mortality and hepatocellular carcinoma and should be considered in all patients with chronic HCV infection.INSERM-ANRS (France Recherche NordSud Sida-HIV Hépatites), ANR (Agence Nationale de la Recherche), DGS (Direction Générale de la Santé), MSD, Janssen, Gilead, AbbVie, Bristol-Myers Squibb, and Roche.
Published: 2019
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48. New treatments/targets for primary biliary cholangitis

Author: Olivier Chazouillères, Raoul Poupon, and Christophe Corpechot
Subjects: medicine.medical_specialty, Standard of care, Cirrhosis, Review, Chronic liver disease, PBC, PPAR, digestive system, chemistry.chemical_compound, Liver disease, obeticholic acid, Cholestasis, Internal Medicine, medicine, Immunology and Allergy, lcsh:RC799-869, Intensive care medicine, Hepatology, business.industry, Gastroenterology, Obeticholic acid, Treatment options, medicine.disease, Ursodeoxycholic acid, digestive system diseases, ursodeoxycholic acid, chemistry, FXR, inflammation, lcsh:Diseases of the digestive system. Gastroenterology, fibrates, business, cholestasis, liver disease, medicine.drug
Abstract: Summary: Primary biliary cholangitis (PBC) is an autoimmune, cholestatic, chronic liver disease that ultimately progresses towards cirrhosis and liver failure if untreated. While ursodeoxycholic acid has been established as standard of care for PBC in the last few decades, significant advances in second-line treatment options have recently been made and new therapeutic developments are currently under evaluation. The purpose of this article is to provide the clinician with an overview of the current treatment options and future opportunities for patients with PBC. Keywords: PBC, ursodeoxycholic acid, obeticholic acid, fibrates, FXR, PPAR, cholestasis, inflammation, liver disease
Published: 2019

49. Fungi participate in the dysbiosis of gut microbiota in patients with primary sclerosing cholangitis

Author: Christophe Corpechot, Olivier Chazouillères, Astrid Kemgang, Sarah Jegou, Marjolène Straube, Karima Ben Belkacem, Chantal Housset, Sara Lemoinne, Harry Sokol, Centre de Référence des Maladies Rares - Maladies Inflammatoires des Voies Biliaires et Service d’Hépatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Université Paris Saclay (COmUE), Laboratoire des biomolécules (LBM UMR 7203), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Gestionnaire, HAL Sorbonne Université 5, Sorbonne Universités (COMUE), European Association for the Study of the Liver (EASL). CHE., Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Université Pierre et Marie Curie (Paris 6), École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-ESPCI ParisTech-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-ESPCI ParisTech-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-Gastroentérologie [CHU Pitié-Salpêtrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP]
Subjects: endocrine system diseases, [SDV]Life Sciences [q-bio], Gut flora, Inflammatory bowel disease, digestive system, Primary sclerosing cholangitis, 03 medical and health sciences, 0302 clinical medicine, Exophiala, inflammatory bowel disease, medicine, In patient, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, gut microbiota, digestive, oral, and skin physiology, Gastroenterology, Healthy subjects, primary sclerosing cholangitis, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, biology.organism_classification, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, digestive system diseases, [SDV] Life Sciences [q-bio], stomatognathic diseases, Immunology, 030211 gastroenterology & hepatology, fungi, Dysbiosis, Bacteria, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: ObjectivePatients with primary sclerosing cholangitis (PSC) were previously shown to display a bacterial gut dysbiosis but fungal microbiota has never been examined in these patients. The aim of this study was to assess the fungal gut microbiota in patients with PSC.DesignWe analysed the faecal microbiota of patients with PSC and concomitant IBD (n=27), patients with PSC and no IBD (n=22), patients with IBD and no PSC (n=33) and healthy subjects (n=30). Bacterial and fungal composition of the faecal microbiota was determined using 16S and ITS2 sequencing, respectively.ResultsWe found that patients with PSC harboured bacterial dysbiosis characterised by a decreased biodiversity, an altered composition and a decreased correlation network density. These alterations of the microbiota were associated with PSC, independently of IBD status. For the first time, we showed that patients with PSC displayed a fungal gut dysbiosis, characterised by a relative increase in biodiversity and an altered composition. Notably, we observed an increased proportion of Exophiala and a decreased proportion of Saccharomyces cerevisiae. Compared with patients with IBD and healthy subjects, the gut microbiota of patients with PSC exhibited a strong disruption in bacteria-fungi correlation network, suggesting an alteration in the interkingdom crosstalk.ConclusionThis study demonstrates that bacteria and fungi contribute to gut dysbiosis in PSC.
Published: 2019
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50. SAT-490-No Impact of Direct-Acting Antivirals on Recurrent Hepatocellular Carcinoma Tumour Growth in the ANRS CO22 Hepather Cohort

Author: Tarik Asselah, Pol Stanislas, Fabien Zoulim, Isabelle Rosa, A.V. Pichard, Hélène Fontaine, Olivier Chazouillères, Correas Jean Michel, Dominique Larrey, Marc Bourlière, Nathalie Ganne, Véronique Loustaud-Ratti, Jérôme Gournay, Philippe Mathurin, Vincent Leroy, Albert Tran, Jean-Pierre Bronowicki, Didier Samuel, Dorival Celine, Dominique Guyader, Paul Calès, Christophe Hézode, Metivier Sophie, Victor de Ledinghen, Fabrice Carrat, Département d'hépatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hospices Civils de Lyon, Departement de Neurologie (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Lille, Épidémiologie clinique des maladies virales chroniques [iPLesp] (CLEPIVIR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Physiopathologie du système immunitaire (Inserm U1223), and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: Oncology, medicine.medical_specialty, Hepatology, business.industry, Internal medicine, [SDV]Life Sciences [q-bio], Cohort, Medicine, business, DIRECT ACTING ANTIVIRALS, Recurrent Hepatocellular Carcinoma
Abstract: International audience
Published: 2019
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