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1. 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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2. 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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3. 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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4. 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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5. The Complementary Value of Magnetic Resonance Imaging and Vibration-Controlled Transient Elastography for Risk Stratification in Primary Sclerosing Cholangitis

Author

Farid Gaouar, Palak J. Trivedi, Sara Lemoinne, Francesco Paolo Russo, Olivier Chazouillères, Astrid Kemgang, Chantal Housset, Nora Cazzagon, Christophe Corpechot, Raffaella Motta, Sanaâ El Mouhadi, Karima Ben Belkacem, Annarosa Floreani, Yves Chretien, Gideon M. Hirschfield, and Lionel Arrivé

Subjects
Adult, Male, medicine.medical_specialty, endocrine system diseases, Cholangitis, medicine.medical_treatment, Cholangitis, Sclerosing, Comorbidity, Liver transplantation, Risk Assessment, Vibration, digestive system, Primary sclerosing cholangitis, Cholangiocarcinoma, 03 medical and health sciences, 0302 clinical medicine, Cholangiography, Liver stiffness, medicine, Humans, Progression-free survival, Hepatology, medicine.diagnostic_test, Liver Cirrhosis, Biliary, business.industry, digestive, oral, and skin physiology, Gastroenterology, Magnetic resonance imaging, Middle Aged, Inflammatory Bowel Diseases, Prognosis, equipment and supplies, medicine.disease, Magnetic Resonance Imaging, Shock, Septic, Progression-Free Survival, digestive system diseases, Liver Transplantation, Liver, 030220 oncology & carcinogenesis, Risk stratification, Elasticity Imaging Techniques, Female, 030211 gastroenterology & hepatology, Radiology, Transient elastography, business
Abstract

Magnetic resonance (MR) risk scores and liver stiffness (LS) have individually been shown to predict clinical outcomes in primary sclerosing cholangitis (PSC). The aim of this study was to assess their complementary prognostic value.Patients with PSC from 3 European centers with a 3-dimensional MR cholangiography available for central reviewing and a valid LS measurement assessed by vibration-controlled transient elastography by FibroScan performed within a 6-month interval were included in a longitudinal retrospective study. The MR score (Anali) without gadolinium (Gd) was calculated according to the formula: (1 × dilatation of intrahepatic bile ducts) + (2 × dysmorphy) + (1 × portal hypertension). The primary end point was survival without liver transplantation or cirrhosis decompensation. The prognostic values of LS and Anali score without Gd were assessed using Cox proportional hazard models.One hundred sixty-two patients were included. Over a total follow-up of 753 patient-years, 40 patients experienced an adverse outcome (4 liver transplantations, 6 liver-related deaths, and 30 cirrhosis decompensations). LS and Anali score without Gd were significantly correlated (ρ = 0.51, P0.001) and were independently associated with the occurrence of an adverse outcome. Optimal prognostic thresholds were 10.5 kPa for LS and 2 for the Anali score without Gd. Hazard ratios (95% confidence interval) were 2.07 (1.06-4.06) and 3.78 (1.67-8.59), respectively. The use in combination of these 2 thresholds allowed us to separate patients into low-, medium-, and high-risk groups for developing adverse outcomes. The 5-year cumulative rates of adverse outcome in these 3 groups were 8%, 16%, and 38% (P0.001), respectively.The combined use of MRI and vibration-controlled transient elastography permits easy risk stratification of patients with PSC.

Published
2019

6. Effects of Tumor Necrosis Factor Antagonists in Patients With Primary Sclerosing Cholangitis

Author

Karima Ben Belkacem, Neta Gotlieb, Severine Vermeire, Christoph Schramm, Roger W. Chapman, Nicholas Fonseca Nogueira, Emma Nilsson, Henriette Ytting, Hanns-Ulrich Marschall, João Sabino, Sven Almer, Cyriel Y. Ponsioen, Geir Larsson, Kate D. Lynch, Gina Sado, Ellina Lytvyak, Douglas Thorburn, Bjørn Moum, Olivier Chazouillères, Oren Shibolet, Kim N. van Munster, Christian Rupp, Alessandra Zago, Fredrik Rorsman, Christopher L. Bowlus, K. K. Jørgensen, Cynthia Levy, Mette Vesterhus, Alessio Gerussi, Charlotte R H Hedin, Francesca Saffioti, Aldo J. Montano-Loza, Andrew Mason, Nora Cazzagon, Annika Bergquist, Nelson Ndegwa, Graduate School, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, Hedin, C, Sado, G, Ndegwa, N, Lytvyak, E, Mason, A, Montano-Loza, A, Gerussi, A, Saffioti, F, Thorburn, D, Nilsson, E, Larsson, G, Moum, B, van Munster, K, Ponsioen, C, Levy, C, Nogueira, N, Bowlus, C, Gotlieb, N, Shibolet, O, Lynch, K, Chapman, R, Rupp, C, Vesterhus, M, Jorgensen, K, Rorsman, F, Schramm, C, Sabino, J, Vermeire, S, Zago, A, Cazzagon, N, Marschall, H, Ytting, H, Ben Belkacem, K, Chazouilleres, O, Almer, S, and Bergquist, A

Subjects
musculoskeletal diseases, medicine.medical_specialty, Exacerbation, Cholangitis, Sclerosing, digestive system, Inflammatory bowel disease, Gastroenterology, Primary sclerosing cholangitis, Anti-Inflammatory, 03 medical and health sciences, 0302 clinical medicine, Hepatic, MED/12 - GASTROENTEROLOGIA, Interquartile range, Internal medicine, medicine, Adalimumab, Humans, Retrospective Studies, Hepatology, Tumor Necrosis Factor-alpha, business.industry, Inflammatory Bowel Diseases, medicine.disease, Infliximab, digestive system diseases, Intestine, Liver Transplantation, 030220 oncology & carcinogenesis, Tumor Necrosis Factor Inhibitors, 030211 gastroenterology & hepatology, Liver function, MED/09 - MEDICINA INTERNA, Calprotectin, business, medicine.drug
Abstract

Background & Aims: Few patients with primary sclerosing cholangitis (PSC) and inflammatory bowel diseases (IBDs) are exposed to tumor necrosis factor (TNF) antagonists because of the often mild symptoms of IBD. We assessed the effects of anti-TNF agents on liver function in patients with PSC and IBD, and their efficacy in treatment of IBD. Methods: We performed a retrospective analysis of 141 patients with PSC and IBD receiving treatment with anti-TNF agents (infliximab or adalimumab) at 20 sites (mostly tertiary-care centers) in Europe and North America. We collected data on the serum level of alkaline phosphatase (ALP). IBD response was defined as either endoscopic response or, if no endoscopic data were available, clinical response, as determined by the treating clinician or measurements of fecal calprotectin. Remission was defined more stringently as endoscopic mucosal healing. We used linear regression analysis to identify factors associated significantly with level of ALP during anti-TNF therapy. Results: Anti-TNF treatment produced a response of IBD in 48% of patients and remission of IBD in 23%. There was no difference in PSC symptom frequency before or after drug exposure. The most common reasons for anti-TNF discontinuation were primary nonresponse of IBD (17%) and side effects (18%). At 3 months, infliximab-treated patients had a median reduction in serum level of ALP of 4% (interquartile range, reduction of 25% to increase of 19%) compared with a median 15% reduction in ALP in adalimumab-treated patients (interquartile range, reduction of 29% to reduction of 4%; P =.035). Factors associated with lower ALP were normal ALP at baseline (P

Published
2020
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7. FRI-009-Bezafibrate add-on therapy in high-risk primary biliary cholangitis is associated with prolonged predicted survival even in patients with incomplete biochemical improvements

Author

Alexandra Rousseau, Christophe Corpechot, Olivier Chazouillères, Sara Lemoinne, Karima Ben Belkacem, Gaouar Farid, and Raoul Poupon

Subjects
Add on therapy, medicine.medical_specialty, Bezafibrate, Hepatology, business.industry, Internal medicine, medicine, In patient, business, Gastroenterology, medicine.drug
Published
2019
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8. PS-185-Magnetic resonance risk score and liver stiffness by transient elastography have complementary prognostic values in patients with primary sclerosing cholangitis

Author

Lionel Arrivé, Francesco Russo, Olivier Chazouillères, Nora Cazzagon, Sara Lemoinne, Farid Gaouar, Astrid Donald Kemgang Fankem, Palak J. Trivedi, Annarosa Floreani, Christophe Corpechot, Gideon M. Hirschfield, Raffaella Motta, Sanaa El Mouhadi, Chantal Housset, Karima Ben Belkacem, and Yves Chretien

Subjects
medicine.medical_specialty, Framingham Risk Score, Hepatology, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, medicine.disease, Primary sclerosing cholangitis, Liver stiffness, Medicine, In patient, Radiology, business, Transient elastography
Published
2019
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9. FRI-010-Bezafibrate add-on therapy in high-risk primary biliary cholangitis is associated with an improvement of fibrometer and fibrometer-VCTE, two high-accuracy non-invasive fibrosis tests extensively validated in frequent chronic liver diseases

Author

Olivier Chazouillères, Raoul Poupon, Alexandra Rousseau, Gaouar Farid, Sara Lemoinne, Christophe Corpechot, Paul Calès, and Karima Ben Belkacem

Subjects
medicine.medical_specialty, Bezafibrate, Hepatology, FIBROMETER, business.industry, Non invasive, medicine.disease, Gastroenterology, Add on therapy, Fibrosis, Internal medicine, Medicine, business, medicine.drug
Published
2019
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10. Primary sclerosing cholangitis response to the combination of fibrates with ursodeoxycholic acid: French–Spanish experience

Author

Farid Gaouar, Olivier Chazouillères, Astrid Donald Kemgang Fankem, Christophe Corpechot, Anna Reig, Sara Lemoinne, Chantal Housset, Albert Parés, Karima Ben Belkacem, Raoul Poupon, 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 (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 d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, Universitat de Barcelona (UB), Gestionnaire, Hal Sorbonne Université, Centre de Recherche Saint-Antoine (CRSA), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)

Subjects
Male, Cholagogues and Choleretics, Cirrhosis, Gastroenterology, 0302 clinical medicine, Fenofibrate, Liver Function Tests, Chronic liver diseases, Hypolipidemic Agents, Cholestasis, Ursodeoxycholic Acid, Middle Aged, Ursodeoxycholic acid, 3. Good health, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Female, France, medicine.drug, Adult, medicine.medical_specialty, Cholangitis, Sclerosing, Liver fibrosis, Primary sclerosing cholangitis, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, Adverse effect, Aged, Retrospective Studies, Bezafibrate, Hepatology, business.industry, Pruritus, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Alkaline Phosphatase, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Discontinuation, Spain, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, business
Abstract

Summary Background & aims In patients with primary sclerosing cholangitis (PSC), ursodeoxycholic acid (UDCA) treatment improves serum liver tests and surrogate markers of prognosis but has no proven effect on survival. Additional therapies are obviously needed. Fibrates, PPAR agonists with anti-cholestatic properties, have a beneficial effect in primary biliary cholangitis. The aim of this study was to evaluate the safety and efficacy of fibrates in PSC patients. Methods Retrospectively, we investigated PSC patients treated with fibrates (fenofibrate 200 mg/day or bezafibrate 400 mg/day) for at least 6 months in addition to UDCA, after an incomplete biochemical response (alkaline phosphatase [ALP] ≥ 1.5 × upper limit of normal) to UDCA. Changes in biochemical parameters and clinical features were assessed. Results Twenty patients were included (fourteen from Paris and six from Barcelona): median age 43.8 years, median liver stiffness 11 kPa (≥ F3). Upon treatment with fibrates (median duration of 1.56 years), liver tests significantly improved, including a reduction of ALP levels by 41% and pruritus significantly decreased. No serious adverse event attributable to fibrates occurred. Discontinuation of fibrates was followed by a clear rebound of ALP. Despite biochemical improvement, liver stiffness significantly increased. Conclusions Combining UDCA with fibrates results in a significant biochemical improvement and pruritus decrease in PSC patients with incomplete response to UDCA. These results provide a rationale for larger and prospectively designed studies to establish the efficacy and safety of fibrates in PSC.

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