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1. Anticoagulation is not associated with an increased risk of variceal bleeding under systemic therapy for advanced HCC

Author: Manon Allaire, Philippe Sultanik, and Dominique Thabut
Subjects: Diseases of the digestive system. Gastroenterology, RC799-869
Published: 2024
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2. Proton pump inhibitor use and risk of hepatic encephalopathy: A multicentre study

Author: Simon Johannes Gairing, Chiara Mangini, Lisa Zarantonello, Elise Jonasson, Henrike Dobbermann, Philippe Sultanik, Peter Robert Galle, Joachim Labenz, Dominique Thabut, Jens Uwe Marquardt, Patricia P. Bloom, Mette Munk Lauridsen, Sara Montagnese, and Christian Labenz
Subjects: Covert hepatic encephalopathy, Decompensated cirrhosis, Psychometric hepatic encephalopathy score, Acid suppression, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: Data on the association between proton pump inhibitor (PPI) use and hepatic encephalopathy (HE) are conflicting, and data from multicentre studies are scarce. The aim of this study was to dissect the potential association between PPI use and minimal (MHE) and overt HE (OHE). Methods: Data from patients with cirrhosis recruited at seven centres across Europe and the US were analysed. MHE was defined by the psychometric hepatic encephalopathy score (PHES). PPI use was recorded on the day of testing with PHES. Patients were followed for OHE development and death/liver transplantation. Results: A total of 1,160 patients with a median MELD of 11 were included (Child-Pugh stages: A 49%/B 39%/C 11%). PPI use was noted in 58% of patients. Median follow-up time was 18.1 months, during which 230 (20%) developed an OHE episode, and 224 (19%) reached the composite endpoint of death/liver transplantation. In multivariable analyses, PPI use was neither associated with the presence of MHE at baseline nor OHE development during follow-up. These findings were consistent in subgroup analyses of patients with Child-Pugh A or B cirrhosis and after excluding patients with a history of OHE. PPI use was also not associated with a higher risk of OHE, neither in patients with an indication for treatment nor in patients without an indication. Conclusions: PPI use is not associated with a higher risk of HE in patients with cirrhosis. Based on these findings, at present, a prescription should not be prohibited in case of a generally accepted indication. Impact and implications: Data on the association between proton pump inhibitor (PPI) use and hepatic encephalopathy (HE) are conflicting. In this study, PPI use was not associated with a higher risk of minimal HE at baseline or overt HE during follow-up in patients with cirrhosis. Based on these findings, prescription of a PPI for a generally accepted indication should not be prohibited in patients with cirrhosis.
Published: 2024
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3. Protein-S-100-beta is increased in patients with decompensated cirrhosis admitted to ICU

Author: Nicolas Weiss, Simona Tripon, Maxime Mallet, Françoise Imbert-Bismut, Mehdi Sakka, Dominique Bonnefont-Rousselot, Philippe Sultanik, Sarah Mouri, Marika Rudler, and Dominique Thabut
Subjects: Cirrhosis, Hepatic encephalopathy, Blood–brain barrier, PS100-Beta, Liver disease, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: Background: Hepatic encephalopathy (HE) is highly prevalent in patients with liver diseases. The pathophysiology of HE is centered on the synergic role of hyperammonemia and systemic inflammation. However, some data suggest altered functioning of the blood–brain barrier (BBB). Assessing BBB function is challenging in clinical practice and at the bedside. Protein-S-100 Beta (PS100-Beta) could be a useful peripheral marker of BBB permeability in HE. This study aimed to assess plasmatic PS100-Beta levels in a prospective cohort of patients admitted to the intensive care unit (ICU) with decompensated cirrhosis with and without overt HE. Methods: We retrospectively evaluated a prospective cohort of cirrhotic patients admitted to the ICU from October 2013 to September 2015 that had an available plasmatic PS100-Beta measurement. Patients with previous neurological impairment or limitation of intensive or resuscitative measures were excluded. Overt HE was defined as West-Haven grades 2 to 4. The patients were compared to a control cohort of outpatient clinic cirrhotic and non-cirrhotic patients explored for isolated elevation of liver enzymes. After ICU discharge, the patients were followed for at least 3 months for the occurrence of overt HE. Adverse outcomes (liver transplantation or death) were collected. The ability of PS100-Beta – in combination with other factors – to predict overt HE was evaluated in a multivariate analysis using logistic regression. Likelihood ratios were used to determine the effects and calculate odds ratios (OR). Survival analysis was performed by using the Kaplan–Meier method and survival between groups was compared using a Log-rank test. Results: A total of 194 ICU patients and 207 outpatients were included in the study. Increased levels of plasmatic PS100-Beta were detected in the ICU decompensated cirrhotic patients compared with the outpatients ([0.15±0.01] mg/L vs. [0.08±0] mg/L, P
Published: 2024
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4. Identification of an Endoglin Variant Associated With HCV-Related Liver Fibrosis Progression by Next-Generation Sequencing

Author: Frédégonde About, Stéphanie Bibert, Emmanuelle Jouanguy, Bertrand Nalpas, Lazaro Lorenzo, Vimel Rattina, Mohammed Zarhrate, Sylvain Hanein, Mona Munteanu, Beat Müllhaupt, David Semela, Nasser Semmo, Jean-Laurent Casanova, Ioannis Theodorou, Philippe Sultanik, Thierry Poynard, Stanislas Pol, Pierre-Yves Bochud, Aurélie Cobat, Laurent Abel, The Swiss Hepatitis C Cohort Study Group, The French ANRS HC EP 26 Genoscan Study Group, Francesco Negro, Antoine Hadengue, Laurent Kaiser, Laura Rubbia-Brandt, Darius Moradpour, Cristina Cellerai, Martin Rickenbach, Andreas Cerny, Gladys Martinetti, Jean-François Dufour, Meri Gorgievski, Virginie Masserey Spicher, Markus Heim, Hans Hirsch, Beat Helbling, Stephan Regenass, Raffaele Malinverni, Guenter Dollenmaier, and Gieri Cathomas
Subjects: endoglin, HCV-related liver fibrosis, exome sequencing, TGF-beta, rare-variant association study, Genetics, QH426-470
Abstract: Despite the astonishing progress in treating chronic hepatitis C virus (HCV) infection with direct-acting antiviral agents, liver fibrosis remains a major health concern in HCV infected patients, in particular due to the treatment cost and insufficient HCV screening in many countries. Only a fraction of patients with chronic HCV infection develop liver fibrosis. While there is evidence that host genetic factors are involved in the development of liver fibrosis, the common variants identified so far, in particular by genome-wide association studies, were found to have limited effects. Here, we conducted an exome association study in 88 highly selected HCV-infected patients with and without fibrosis. A strategy focusing on TGF-β pathway genes revealed an enrichment in rare variants of the endoglin gene (ENG) in fibrosis patients. Replication studies in additional cohorts (617 patients) identified one specific ENG variant, Thr5Met, with an overall odds ratio for fibrosis development in carriers of 3.04 (1.39–6.69). Our results suggest that endoglin, a key player in TGF-β signaling, is involved in HCV-related liver fibrogenesis.
Published: 2019
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5. Inhibition of DPP4 activity in humans establishes its in vivo role in CXCL10 post‐translational modification: prospective placebo‐controlled clinical studies

Author: Jérémie Decalf, Kristin V Tarbell, Armanda Casrouge, Jeffrey D Price, Grace Linder, Estelle Mottez, Philippe Sultanik, Vincent Mallet, Stanislas Pol, Darragh Duffy, and Matthew L Albert
Subjects: chemokines, clinical study, CXCL10, DPP4, post‐translational modifications, Medicine (General), R5-920, Genetics, QH426-470
Abstract: Abstract Biochemical experiments, animal models, and observational studies in humans all support a role of dipeptidyl peptidase 4 (DPP4) in the N‐terminal truncation of CXCL10, which results in the generation of an antagonist form of the chemokine that limits T‐cell and NK cell migration. Motivated by the ability to regulate lymphocyte trafficking in vivo, we conducted two prospective clinical trials to test the effects of DPP4 inhibition on CXCL10 processing in healthy donors and in chronic hepatitis C patients, a disease in which DPP4 levels are found to be elevated. Participants were treated daily with 100 mg sitagliptin, a clinically approved DPP4 inhibitor. Plasma samples were analyzed using an ultrasensitive single‐molecule assay (Simoa) to distinguish the full‐length CXCL101–77 from the NH2‐truncated CXCL103–77, as compared to the total CXCL10 levels. Sitagliptin treatment resulted in a significant decrease in CXCL103–77 concentration, a reciprocal increase in CXCL101–77, with only minimal effects on total levels of the chemokine. These data provide the first direct evidence that in vivo DPP4 inhibition in humans can preserve the bioactive form of CXCL10, offering new therapeutic opportunities for DPP4 inhibitors.
Published: 2016
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6. Unsolved Questions in Salvage TIPSS: Practical Modalities for Placement, Alternative Therapeutics, and Long-Term Outcomes

Author: Charlotte Bouzbib, Philippe Sultanik, Dominique Thabut, and Marika Rudler
Subjects: Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Salvage transjugular intrahepatic portosystemic shunt (TIPSS) has proven its efficacy to treat refractory variceal bleeding for patients with cirrhosis. However, this procedure is associated with very poor outcomes. As it is used as a last resort to treat a severe complication of cirrhosis, it seems essential to improve our practice, with the aim of optimizing management of those patients. Somehow, many questions are still unsolved: which stents should be used? Should a concomitant embolization be systematically considered? Is there any alternative therapeutic in case of recurrent bleeding despite TIPSS? What are the long-term outcomes on survival, liver transplantation, and hepatic encephalopathy after salvage TIPSS? Is this procedure futile in some patients? Is prognosis with salvage TIPSS nowadays as bad as earlier, despite the improvement of prophylaxis for variceal bleeding? The aim of this review is to summarize those data and to identify the lacking ones to guide further research on salvage TIPSS.
Published: 2019
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7. Bystander hyperactivation of preimmune CD8+ T cells in chronic HCV patients

Author: Cécile Alanio, Francesco Nicoli, Philippe Sultanik, Tobias Flecken, Brieuc Perot, Darragh Duffy, Elisabetta Bianchi, Annick Lim, Emmanuel Clave, Marit M van Buuren, Aurélie Schnuriger, Kerstin Johnsson, Jeremy Boussier, Antoine Garbarg-Chenon, Laurence Bousquet, Estelle Mottez, Ton N Schumacher, Antoine Toubert, Victor Appay, Farhad Heshmati, Robert Thimme, Stanislas Pol, Vincent Mallet, and Matthew L Albert
Subjects: Pre-immune repertoire, CD8 T cell dysfunction, TCR signaling, viral immunology, chronic inflammation, Medicine, Science, Biology (General), QH301-705.5
Abstract: Chronic infection perturbs immune homeostasis. While prior studies have reported dysregulation of effector and memory cells, little is known about the effects on naïve T cell populations. We performed a cross-sectional study of chronic hepatitis C (cHCV) patients using tetramer-associated magnetic enrichment to study antigen-specific inexperienced CD8+ T cells (i.e., tumor or unrelated virus-specific populations in tumor-free and sero-negative individuals). cHCV showed normal precursor frequencies, but increased proportions of memory-phenotype inexperienced cells, as compared to healthy donors or cured HCV patients. These observations could be explained by low surface expression of CD5, a negative regulator of TCR signaling. Accordingly, we demonstrated TCR hyperactivation and generation of potent CD8+ T cell responses from the altered T cell repertoire of cHCV patients. In sum, we provide the first evidence that naïve CD8+ T cells are dysregulated during cHCV infection, and establish a new mechanism of immune perturbation secondary to chronic infection.
Published: 2015
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8. Impact of IL28B, APOH and ITPA Polymorphisms on Efficacy and Safety of TVR- or BOC-Based Triple Therapy in Treatment-Experienced HCV-1 Patients with Compensated Cirrhosis from the ANRS CO20-CUPIC Study.

Author: Frédégonde About, Tiphaine Oudot-Mellakh, Jonathan Niay, Pascaline Rabiéga, Vincent Pedergnana, Darragh Duffy, Philippe Sultanik, Carole Cagnot, Fabrice Carrat, Patrick Marcellin, Fabien Zoulim, Dominique Larrey, Christophe Hézode, Hélène Fontaine, Jean-Pierre Bronowicki, Stanislas Pol, Matthew L Albert, Ioannis Theodorou, Aurélie Cobat, Laurent Abel, and ANRS CO20-CUPIC study group
Subjects: Medicine, Science
Abstract: BACKGROUND:Human genetic factors influence the outcome of pegylated interferon and ribavirin hepatitis C therapy. We explored the role of IL28B, APOH and ITPA SNPs on the outcomes of triple therapy including telaprevir or boceprevir in patients with compensated cirrhosis chronically infected with HCV-1. PATIENTS AND METHODS:A total of 256 HCV-1 Caucasian treatment-experienced patients with compensated cirrhosis from the ANRS CO20-CUPIC cohort were genotyped for a total of 10 candidate SNPs in IL28B (rs12979860 and rs368234815), APOH (rs8178822, rs12944940, rs10048158, rs52797880, rs1801689 and rs1801690) and ITPA (rs1127354 and rs7270101). We tested the association of IL28B and APOH SNPs with sustained virological response and of ITPA SNPs with anemia related phenotypes by means of logistic regression assuming an additive genetic model. RESULTS:None of the six APOH SNPs were associated with sustained virological response. The favorable alleles of the IL28B SNPs rs12979860 and rs368234815 were associated with sustained virological response (rs12979860: OR = 2.35[1.50-3.70], P = 2x10(-4)). Refined analysis showed that the effect of IL28B SNPs on sustained virological response was restricted to prior PegIFN/RBV relapse (OR = 3.80[1.82-8.92], P = 8x10(-4)). We also confirmed the association between ITPA low activity alleles and protection against early hemoglobin decline in triple therapy (P = 2x10(-5)). CONCLUSION:Our results suggest that the screening of rs12979860 may remain interesting for decision making in prior relapse HCV-1 Caucasian patients with compensated cirrhosis eligible for a telaprevir- or boceprevir-based therapy.
Published: 2015
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9. P45 Multimodal Assessment of Covert Hepatic Encephalopathy and Its Outcome in a Prospective Cohort of Outpatients With Chronic Liver Disease

Author: Philippe, Sultanik, primary, Kheloufi, Lyes, additional, Leproux, Apolline, additional, Santiago, Antoine, additional, Bouzbib, Charlotte, additional, Mouri, Sarah, additional, Plessier, Aurélie, additional, Sobesky, Rodolphe, additional, Coilly, Audrey, additional, Galanaud, Damien, additional, Navarro, Vincent, additional, Rudler, Marika, additional, Weiss, Nicolas, additional, and Thabut, Dominique, additional
Published: 2023
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10. P25 Cognitive Differential Diagnosis of Hepatic Encephalopathy in a Cohort of Outpatients With Chronic Liver Disease

Author: Lyès, Kheloufi, primary, Philippe, Sultanik, additional, Leproux, Apolline, additional, Santiago, Antoine, additional, Bouzbib, Charlotte, additional, Mouri, Sarah, additional, Rudler, Marika, additional, Weiss, Nicolas, additional, and Thabut, Dominique, additional
Published: 2023
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11. A history of variceal bleeding is associated with further bleeding under atezolizumab–bevacizumab in patients with <scp>HCC</scp>

Author: Edouard Larrey, Bertille Campion, Manon Evain, Philippe Sultanik, Lorraine Blaise, Héloïse Giudicelli, Mathilde Wagner, Philippe Cluzel, Marika Rudler, Nathalie Ganne‐Carrié, Dominique Thabut, and Manon Allaire
Subjects: Male, Bevacizumab, Liver Cirrhosis, Carcinoma, Hepatocellular, Hepatology, Liver Neoplasms, Humans, Prospective Studies, Sorafenib, Esophageal and Gastric Varices, Gastrointestinal Hemorrhage, Retrospective Studies
Abstract: Atezolizumab-bevacizumab is the new standard for advanced hepatocellular carcinoma (HCC) but its impact on portal hypertension (PHT) is unknown. We aimed to identify predictive factors of acute variceal bleeding (AVB) and to monitor PHT parameters under treatment.We conducted a prospective study including all cirrhotic patients treated with atezolizumab-bevacizumab since 2020. We performed monitoring of PHT using upper endoscopy at inclusion and at 6 months and hepatic venous pressure gradient (HVPG) at inclusion, 3 and 6 months after the beginning of treatment. We also included a retrospective series of patients treated with sorafenib. Time-to-events data were estimated by Kaplan-Meier with the log-rank test, along with Cox models.Forty-three patients treated with atezolizumab-bevacizumab were included (male 79.1%, Child-Pugh A 86%). At baseline, 48.8% were treated with curative anticoagulation, 16.3% already experienced AVB and 25.6% had large oesophageal varices (EV). Sorafenib group characteristics were similar. Vascular invasion was present in 60.5% and median was HVPG 8.5 mm Hg. No significant modification in HVPG and EV size was observed at 6 months in the whole cohort but also when considering vascular invasion and radiological response. 14% presented AVB within a median time of occurrence of 3 months, without bleeding-related death. In multivariate analysis, history of AVB (HR = 10.58, p = .03) was associated with AVB. AVB incidence was higher in atezolizumab-bevacizumab compared to sorafenib group (21% vs. 5% at 1 year, p = .02).Atezolizumab-bevacizumab treatment was associated with a higher risk of AVB compared to sorafenib. A history of AVB was associated with AVB during follow-up, which questions the use of bevacizumab in this setting.
Published: 2022
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12. Current challenges and future perspectives in treating patients with NAFLD-related cirrhosis

Author: Maxime Mallet, Cristina Alina Silaghi, Philippe Sultanik, Filomena Conti, Marika Rudler, Vlad Ratziu, Dominique Thabut, and Raluca Pais
Subjects: Hepatology
Published: 2023
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13. Primary balloon dacryoplasty for nasolacrimal duct obstruction in adults: a systematic review

Author: Pauline Beaujeux, Hakim Benkhatar, Philippe Sultanik, Edouard Koch, and Barthélémy Poignet
Subjects: Adult, medicine.medical_specialty, Nasolacrimal duct, business.industry, Acquired nasolacrimal duct obstruction, medicine.disease, eye diseases, Surgery, 03 medical and health sciences, Ophthalmology, Stenosis, Treatment Outcome, 0302 clinical medicine, Nasolacrimal duct obstruction, medicine.anatomical_structure, Lacrimal Duct Obstruction, 030221 ophthalmology & optometry, medicine, Humans, 030223 otorhinolaryngology, business, Balloon dacryoplasty, Dacryocystorhinostomy, Nasolacrimal Duct, Minimally invasive procedures
Abstract: Introduction: Acquired nasolacrimal duct obstruction (NLDO) is a major cause of epiphora. Balloon dacryoplasty (BD) is a minimally invasive procedure effectively used for congenital NLDO which has ...
Published: 2020
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14. Optimal management of ascites

Author: Maxime Mallet, Dominique Thabut, Philippe Sultanik, Charlotte Bouzbib, Marika Rudler, CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université - Faculté de Médecine (SU FM), and Sorbonne Université (SU)
Subjects: Liver Cirrhosis, medicine.medical_specialty, Cirrhosis, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Liver transplantation, ascites, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Quality of life, Ascites, medicine, Paracentesis, Humans, Diuretics, Intensive care medicine, Hepatology, medicine.diagnostic_test, business.industry, cirrhosis, portal hypertension, medicine.disease, Liver Transplantation, 3. Good health, 030220 oncology & carcinogenesis, Quality of Life, Portal hypertension, 030211 gastroenterology & hepatology, medicine.symptom, Complication, business
Abstract: International audience; Ascites is the most common complication of cirrhosis, which develops in 5%-10% of patients per year. Its management is based on symptomatic measures including restriction of sodium intake, diuretics and paracentesis. Underlying liver disease must always be treated and may improve ascites. In some patients, ascites is not controlled by medical therapies and has a major impact on quality of life and survival. TIPS placement and liver transplantation must therefore be discussed. More recently, repeated albumin infusions and Alfapump® have emerged as new therapies in ascites. In this review, the current data on these different options are analysed and an algorithm to help the physician make clinical decisions is suggested.
Published: 2020
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15. Blood ammonia in patients with chronic liver diseases: A better defined role in clinical practice

Author: Maxime Mallet, Victor Desplats, Charlotte Bouzbib, Philippe Sultanik, Imen Alioua, Marika Rudler, Nicolas Weiss, and Dominique Thabut
Subjects: Diagnosis, Differential, Liver Cirrhosis, Ammonia, Hepatic Encephalopathy, Biophysics, Brain, Humans, Cell Biology, Molecular Biology, Biochemistry
Abstract: Ammonia is one of the main players in the pathogenesis of hepatic encephalopathy (HE) in patients with chronic liver diseases. The usefulness of measuring ammonemia has been debated since many years. New data reveal that besides helping in the differential diagnosis of HE, ammonemia could be a prognostic marker not only in patients with HE, but also in patients without any neurological symptoms, suggesting a potential toxic role of ammonia beyond the brain. Finally, targeting ammonemia while monitoring therapeutic response could be a way to improve outcomes in patients with HE.
Published: 2021

16. TIPS and liver transplantation should always be discussed together

Author: Eric Savier, Imen Alioua, Marika Rudler, Philippe Sultanik, and Dominique Thabut
Subjects: Liver Cirrhosis, Text mining, Hepatology, business.industry, medicine.medical_treatment, MEDLINE, medicine, Humans, Portasystemic Shunt, Transjugular Intrahepatic, Liver transplantation, Bioinformatics, business, Liver Transplantation
Published: 2021
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17. Transportation and handling of blood samples prior to ammonia measurement in the real life of a large university hospital

Author: Thierry Poynard, Mehdi Sakka, Rana Alkouri, Dominique Thabut, Marika Rudler, Jamal Alfaisal, Sylvie Dever, Françoise Imbert-Bismut, Dominique Bonnefont-Rousselot, Shaedah Djavoudine, Mona Munteanu, Philippe Sultanik, Pierre-Emeric Payet, Fouzi Mestari, Service de Biochimie Métabolique [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), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], Université de Paris (UP), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Institut de Chimie du CNRS (INC)-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), 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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and CCSD, Accord Elsevier
Subjects: 0301 basic medicine, Waiting time, Sample (material), [SDV]Life Sciences [q-bio], Clinical Biochemistry, Centrifugation, Transportation, Context (language use), Biochemistry, Specimen Handling, 03 medical and health sciences, Ammonia, chemistry.chemical_compound, 0302 clinical medicine, Freezing, Humans, Ammonia Measurement, Sample handling, Chromatography, Biochemistry (medical), Temperature, General Medicine, University hospital, Hospitals, [SDV] Life Sciences [q-bio], 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Environmental science
Abstract: Background: Hyperammonemia is neurotoxic and as such can be a medical emergency. Preanalytical factors greatly influence the blood ammonia concentration results. Aims and methods: Ammonia concentrations measured in the real life setting of a large hospital after pneumatic transport of blood samples and various time periods before centrifugation were compared to those based on the indications of the reagent manufacturer. In the same routine context, the effects of waiting times of centrifuged samples or after plasma storage at −20 °C and −80 °C were determined. Results: Despite the pneumatic transport, the lead times for sample arrival to the lab were even longer than those recommended for their complete handling until ammonia assay. Ammonia concentration results were not affected by the pneumatic transport of blood samples and by waiting times up to a maximum of 1.75 h before their centrifugation and 1 h after centrifugation. Ammonia stability was superior when plasma was stored at −80 °C. Conclusion: Pneumatic transport and sample handling in the routine practice of our lab do not affect ammonia concentration results provided that waiting times are limited to 1.75 h before and 1 h after centrifugation and samples are kept cold. Otherwise, it is better to freeze plasma at −80 °C.
Published: 2020
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18. Prognosis of patients undergoing salvage TIPS is still poor in the preemptive TIPS era

Author: Philippe Sultanik, Charlotte Bouzbib, Marika Rudler, Brigitte Bernard-Chabert, Simona Tripon, Maxime Mallet, H. Benosman, Dominique Thabut, Philippe Cluzel, J. Massard, and Filomena Conti
Subjects: Male, medicine.medical_specialty, Poor prognosis, Alcoholic liver disease, Cirrhosis, Esophageal and Gastric Varices, 03 medical and health sciences, 0302 clinical medicine, medicine, Clinical endpoint, Humans, In patient, Hepatic encephalopathy, Retrospective Studies, Salvage Therapy, Hepatology, business.industry, Gastroenterology, Secondary prophylaxis, Middle Aged, Prognosis, medicine.disease, Surgery, Treatment Outcome, 030220 oncology & carcinogenesis, Portal hypertension, Female, 030211 gastroenterology & hepatology, Portasystemic Shunt, Transjugular Intrahepatic, Gastrointestinal Hemorrhage, business
Abstract: Background Salvage transjugular intrahepatic portosystemic shunts (TIPS) are associated with poor prognosis, especially in patients with Child-Pugh C cirrhosis. Since preemptive TIPS improved prophylaxis of variceal bleeding in those patients, recourse to salvage TIPS may now affect patients with a better prognosis. Aim To assess the impact of the preemptive TIPS policy on outcomes after salvage TIPS placement. Methods We conducted a retrospective monocentric study on cirrhotic patients undergoing salvage TIPS with polytetrafluoroethylene-covered stents from 2002 to 2017 (period 1 until February 2011; period 2 after the preemptive TIPS policy in March 2011). The primary endpoint was one-year transplant-free survival. Results We included 106 patients (period 1/2 = 53/53 patients, male gender 82%, age 54 ± 9 years, alcoholic cirrhosis 70%, Child-Pugh score B/C 94%). One-year transplant-free survival was 46.0% during period 1 compared to 40.2% during period 2 (p = 0.65). Amongst 61 patients with history of variceal bleeding, 32 (52.5%) had an inadequate secondary prophylaxis, including 19 (59.4%) with a previous indication of preemptive TIPS. One-year transplant-free survival was 33.2% if inadequate secondary prophylaxis vs 65.2% if adequate (p = 0.008). Independent factors associated with survival were a lower Child-Pugh or MELD score, infection, failure to control bleeding, and hepatic encephalopathy after TIPS. Conclusion Prognosis after salvage TIPS remained poor in our series. Optimizing secondary prophylaxis, including preemptive TIPS placement, should be the main concern to improve prognosis.
Published: 2021
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19. Endoscopic Therapy for Variceal Bleeding: from Patient Preparation to Available Techniques and Rescue Therapies

Author: Philippe Sultanik and Dominique Thabut
Subjects: medicine.medical_specialty, Gastrointestinal bleeding, Resuscitation, Cirrhosis, Blood transfusion, Hepatology, business.industry, Balloon tamponade, medicine.medical_treatment, medicine.disease, Surgery, 03 medical and health sciences, 0302 clinical medicine, Refractory, 030220 oncology & carcinogenesis, Virology, Internal medicine, Intensive care, medicine, 030211 gastroenterology & hepatology, business
Abstract: Gastrointestinal variceal bleeding (VB) is a frequent and severe complication in cirrhosis. Despite improvement in the last decades in the management of VB, the 6-week mortality after bleeding still ranges from 10 to 20%. Here, we review an up-to-date in the global management of VB. The endoscopic hemostatic treatment relies on band ligation for esophageal variceal bleeding and tissue adhesive injection for gastric variceal bleeding. In case of refractory bleeding, self-expanding metal stents or balloon tamponade can both be used as bridge to specific treatment. The use of covered TIPS provided a new step in the management of VB in severe patients, so-called “early-TIPS” in the setting of secondary prophylaxis or in all patients with refractory bleeding. The global management of patients with VB should include volume resuscitation, blood transfusion, and prevention of complications such as renal failure+/-sepsis+/-liver encephalopathy, as they drive the prognosis. Therefore, the rapid control of gastrointestinal bleeding and subsequent organ complications should be performed in specific intensive care units.
Published: 2017
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20. Neurocognitive impairment is associated with erectile dysfunction in cirrhotic patients

Author: Dominique Thabut, Mona Munteanu, Pauline Rivière, Morgan Rouprêt, Simona Tripon, Florian Poullenot, Philippe Sultanik, Maxime Mallet, Ryad Boukherrouf, Marika Rudler, Sara Philonenko, 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), and Service d'Urologie [CHU Pitié-Salpêtrière]
Subjects: medicine.medical_specialty, Cirrhosis, Hepatology, business.industry, [SDV]Life Sciences [q-bio], Gastroenterology, Erectile function, medicine.disease, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Erectile dysfunction, 030220 oncology & carcinogenesis, Internal medicine, medicine, Dementia, 030211 gastroenterology & hepatology, Observational study, In patient, business, Neurocognitive, Hepatic encephalopathy
Abstract: Introduction Erectile dysfunction (ED) is common in patients with chronic diseases. It is evaluated using the International Index of Erectile Function (IIEF5) questionnaire. The relationship between ED and cirrhosis is complex. The aims of our study were (1) to assess the prevalence of ED in cirrhosis and (2) to evaluate factors associated with ED, with a special focus on minimal hepatic encephalopathy (MHE). Methods We performed a prospective, observational study. Patients with cirrhosis were invited to complete the IIEF5 questionnaire. The exclusion criteria were clinical hepatic encephalopathy (HE) and dementia. MHE was evaluated by the psychometric hepatic encephalopathy test score (PHES) and the critical flicker frequency (CFF). Results Between April 2016 and April 2017, 87 patients were included (age: 55 [51–57] years, Child–Pugh score: 8 [7–9], MELD score: 13 [11–16]. Minimal HE was diagnosed in 33% of the patients according to the PHES and in 44% of the patients according to the CFF. ED was diagnosed in 74/87 patients (85%) when compared to 12.5% in healthy controls (p Conclusion ED should be systematically screened in cirrhotics, especially in patients with MHE.
Published: 2019
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21. 'Empirical' retreatment of patients with chronic hepatitis C who failed a first direct-acting antiviral-based regimen

Author: Pauline Trémeaux, J.-F. Meritet, L. Kramer, Arielle R. Rosenberg, A Laurain, Stanislas Pol, and Philippe Sultanik
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Time Factors, Treatment outcome, Genome, Viral, Hepacivirus, Drug resistance, Viral Nonstructural Proteins, Antiviral Agents, Treatment failure, 03 medical and health sciences, 0302 clinical medicine, Viral genetics, Chronic hepatitis, Internal medicine, Drug Resistance, Viral, medicine, Humans, Treatment Failure, Hepatology, business.industry, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, Surgery, Regimen, Treatment Outcome, 030104 developmental biology, Retreatment, Female, 030211 gastroenterology & hepatology, Sofosbuvir, business, Direct acting
Published: 2017
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22. Unsolved Questions in Salvage TIPSS: Practical Modalities for Placement, Alternative Therapeutics, and Long-Term Outcomes

Author: Dominique Thabut, Charlotte Bouzbib, Marika Rudler, Philippe Sultanik, 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), and Sorbonne Université (SU)
Subjects: Liver Cirrhosis, medicine.medical_specialty, Cirrhosis, medicine.medical_treatment, Salvage therapy, Review Article, Liver transplantation, Esophageal and Gastric Varices, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Embolization, lcsh:RC799-869, Intensive care medicine, Hepatic encephalopathy, Salvage Therapy, Modalities, Hepatology, business.industry, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, General Medicine, medicine.disease, 3. Good health, 030220 oncology & carcinogenesis, Concomitant, lcsh:Diseases of the digestive system. Gastroenterology, 030211 gastroenterology & hepatology, Portasystemic Shunt, Transjugular Intrahepatic, Gastrointestinal Hemorrhage, business, Transjugular intrahepatic portosystemic shunt
Abstract: International audience; Salvage transjugular intrahepatic portosystemic shunt (TIPSS) has proven its efficacy to treat refractory variceal bleeding for patients with cirrhosis. However, this procedure is associated with very poor outcomes. As it is used as a last resort to treat a severe complication of cirrhosis, it seems essential to improve our practice, with the aim of optimizing management of those patients. Somehow, many questions are still unsolved: which stents should be used? Should a concomitant embolization be systematically considered? Is there any alternative therapeutic in case of recurrent bleeding despite TIPSS? What are the long-term outcomes on survival, liver transplantation, and hepatic encephalopathy after salvage TIPSS? Is this procedure futile in some patients? Is prognosis with salvage TIPSS nowadays as bad as earlier, despite the improvement of prophylaxis for variceal bleeding? The aim of this review is to summarize those data and to identify the lacking ones to guide further research on salvage TIPSS.
Published: 2019
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23. Mucocele development after endoscopic sinus surgery for nasal polyposis: A long-term analysis

Author: Ollivier Laccourreye, Philippe Sultanik, Pierre Bonfils, Hakim Benkhatar, and Idir Khettab
Subjects: Male, medicine.medical_specialty, Time Factors, medicine.medical_treatment, Mucocele, Physical examination, 03 medical and health sciences, 0302 clinical medicine, Nasal Polyps, Postoperative Complications, Risk Factors, Paranasal Sinuses, medicine, Paranasal Sinus Diseases, Humans, Risk factor, 030223 otorhinolaryngology, Asthma, Retrospective Studies, medicine.diagnostic_test, business.industry, Retrospective cohort study, Endoscopy, Functional endoscopic sinus surgery, Middle Aged, medicine.disease, Marsupialization, Surgery, Nasal Mucosa, Otorhinolaryngology, 030220 oncology & carcinogenesis, Female, Complication, business, Follow-Up Studies
Abstract: The aim of the present study was to determine the prevalence of long-term mucocele development after functional endoscopic sinus surgery (FESS) for nasal polyposis, to search for a statistical relationship with preoperative variables and to analyze the management of this complication. A retrospective analysis of 153 patients who underwent FESS for nasal polyposis, with a minimum of 7 years of follow-up, was performed. Mucocele diagnosis was based on regular clinical and radiologic evaluation. Univariate and multivariate statistical analysis was performed. The postoperative mucocele rate was 13.1% (20 patients). The mean delay between surgery and mucocele diagnosis was 6.25 years. A high preoperative Lund-Mackay score (>19) was a risk factor for postoperative mucocele (p = 0.04). Asthma and aspirin intolerance did not increase the risk of this complication. Endoscopic marsupialization of mucoceles was successful in 19 patients, with only one recurrent frontal mucocele. One patient required external approaches for two frontal mucoceles. In conclusion, mucocele risk after FESS for nasal polyposis is significant, especially in case of a high preoperative Lund-Mackay score (>19). Long-term clinical follow-up is recommended, imaging being prescribed based on symptoms or abnormal findings on clinical examination. Endoscopic marsupialization is very effective, but frontal mucoceles are more likely to recur.
Published: 2018

24. Traitement de l’infection virale B et prévention du carcinome hépatocellulaire

Author: Stanislas Pol, Damien Soudan, and Philippe Sultanik
Subjects: Cirrhotic liver, medicine.medical_specialty, business.industry, Incidence (epidemiology), General Medicine, medicine.disease_cause, medicine.disease, Gastroenterology, digestive system diseases, Virus, Virological response, Interferon, Hepatocellular carcinoma, Internal medicine, medicine, Curative surgery, Carcinogenesis, business, medicine.drug
Abstract: Chronic hepatitis B virus (HBV) infection is a major public health problem. It concerns more than 240 million people over the world. Natural HBV history leads to hepatocellular carcinoma (HCC), developed on cirrhotic liver and/or by direct viral cacinogenesis. HCC incidence is estimated between 0,2 and 1% per year. The risk of HCC development showed a positive correlation with the level of HBV DNA in the sera. This virosuppression, obtained with interferon or analogs, can reduce the incidence of HCC development during chronic HBV infection. In case of HCC curative surgery, sustained virological response showed a protective effect on recurrence development. Guidelines suggest to treat every cirrhotic or highly replicative patients, and to screen every six months chronic HBs antigen carrier to prevent HCC development.
Published: 2015
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25. Plasma apolipoprotein H limits HCV replication and associates with response to NS3 protease inhibitors-based therapy

Author: Matthew L. Albert, Yoann Barthe, Armanda Casrouge, Arnaud Fontanet, Stanislas Pol, Sylvie Lagaye, Hélène Fontaine, Vincent Mallet, Philippe Sultanik, Christophe Hézode, Estelle Mottez, Laurent Abel, Etienne Gayat, Céline Dorival, Fabrice Carrat, Jean-Pierre Bronowicki, Ioannis Theodorou, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'hépatologie, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunobiologie des Cellules Dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie, systèmes d'information, modélisation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Departement d'Hépatho-Gastro-Enterologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre Hospitalier Universitaire Henri Mondor, Centre d'Immunologie Humaine (CIH), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), 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), Immunité et Infection, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Human Genetics of Infectious Diseases, Rockefeller University [New York]-Rockefeller Branch, Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of anesthesiology and critical care medicine, Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Département Infection et Epidémiologie - Department of Infection and Epidemiology, Institut Pasteur [Paris], The CUPIC Cohort study was sponsored and funded by The National Agency for research on Aids and Viral Hepatitis (ANRS), with support by the French Association for the Study of the Liver(AFEF). The authors also wish to acknowledge the Center for Human Immunology for its support of the research project., Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-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), Institut Pasteur [Paris] (IP), CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Centre Hospitalier Universitaire Henri Mondor, Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR113-Université Pierre et Marie Curie - Paris 6 (UPMC), Rockefeller Branch-rockefeller university, Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Centre Hospitalier Universitaire Henri Mondor, Centre d'Immunologie Humaine ( CIH ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR113-Université Pierre et Marie Curie - Paris 6 ( UPMC ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Biomarqueurs CArdioNeuroVASCulaires ( BioCANVAS ), Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris 13 ( UP13 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Département Infection et Epidémiologie
Subjects: Male, MESH : Aged, MESH : Prospective Studies, MESH : Viral Load, MESH : Hepatitis C, Chronic/blood, Hepacivirus, MESH : Virus Replication/drug effects, Polyethylene Glycols, MESH: Molecular Targeted Therapy, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Molecular Targeted Therapy, Prospective Studies, MESH: Ribavirin/therapeutic use, MESH : Proline/analogs & derivatives, MESH: Treatment Outcome, MESH : Hepacivirus/drug effects, MESH: Viral Nonstructural Proteins/metabolism, MESH: Middle Aged, MESH: RNA, Viral/blood, virus diseases, MESH : beta 2-Glycoprotein I/blood, Blood proteins, 3. Good health, beta 2-Glycoprotein I, Area Under Curve, MESH: Hepacivirus/genetics, Drug Therapy, Combination, Oligopeptides, Apolipoprotein H, MESH : Biomarkers/blood, MESH: Hepatitis C, Chronic/drug therapy, Proline, MESH: Hepatitis C, Chronic/blood, virological response, MESH: Proline/analogs & derivatives, MESH : Antiviral Agents/therapeutic use, Antiviral Agents, MESH : Proline/therapeutic use, Boceprevir, MESH : Recombinant Proteins/therapeutic use, Humans, chronic hepatitis C, MESH : Middle Aged, Protease Inhibitors, MESH: Interferon-alpha/therapeutic use, MESH : Predictive Value of Tests, Aged, MESH: Polyethylene Glycols/therapeutic use, MESH : Hepacivirus/genetics, MESH: Humans, Surrogate endpoint, MESH : Humans, MESH: beta 2-Glycoprotein I/blood, MESH: ROC Curve, digestive system diseases, chemistry, MESH: Protease Inhibitors/therapeutic use, Immunology, MESH: Female, Biomarkers, Time Factors, MESH : Viral Nonstructural Proteins/antagonists & inhibitors, MESH : Hepatitis C, Chronic/diagnosis, MESH : Protease Inhibitors/therapeutic use, Viral Nonstructural Proteins, Virus Replication, MESH : Polyethylene Glycols/therapeutic use, HCV protease inhibitor, Telaprevir, MESH: Virus Replication/drug effects, MESH: Proline/therapeutic use, chemistry.chemical_compound, apolipoprotein H, MESH: Hepacivirus/drug effects, MESH : RNA, Viral/blood, MESH : Female, MESH: Hepatitis C, Chronic/diagnosis, MESH : Viral Nonstructural Proteins/metabolism, MESH: Aged, Middle Aged, Viral Load, MESH: Hepacivirus/growth & development, Recombinant Proteins, MESH: Predictive Value of Tests, MESH : Hepacivirus/enzymology, Treatment Outcome, RNA, Viral, biomarker, [SDV.IMM]Life Sciences [q-bio]/Immunology, Biomarker (medicine), Female, France, MESH: Viral Load, MESH : Oligopeptides/therapeutic use, MESH : Time Factors, medicine.drug, MESH : Hepatitis C, Chronic/drug therapy, MESH : Molecular Targeted Therapy, MESH: Biomarkers/blood, MESH: Hepacivirus/enzymology, MESH : Male, MESH : Ribavirin/therapeutic use, MESH : Interferon-alpha/therapeutic use, MESH : Treatment Outcome, Biology, Predictive Value of Tests, MESH: Recombinant Proteins/therapeutic use, Ribavirin, medicine, MESH : France, NS3, MESH: Viral Nonstructural Proteins/antagonists & inhibitors, Hepatology, MESH : Drug Therapy, Combination, MESH: Time Factors, Interferon-alpha, Hepatitis C, Chronic, MESH : Hepacivirus/growth & development, MESH: Male, MESH: Prospective Studies, MESH: France, MESH: Drug Therapy, Combination, ROC Curve, MESH: Antiviral Agents/therapeutic use, MESH: Oligopeptides/therapeutic use, MESH: Area Under Curve, MESH : Area Under Curve, MESH : ROC Curve
Abstract: International audience; BACKGROUND & AIMS:Chronic infection with HCV remains a public health problem with approximately 150 million people infected worldwide. HCV intersects with lipid metabolism for replication and entry; and plasma concentrations of apolipoproteins have been identified as predictors for response to therapy. Herein, we conducted a screen of plasma proteins, including all apolipoproteins, to identify correlates of response to pegylated-interferon/ribavirin (PR) and HCV non-structural protein 3 (NS3) inhibitors (i.e., telaprevir/boceprevir) therapy in treatment-experienced cirrhotic patients from the ANRS CUPIC cohort.METHODS:We analysed 220 baseline plasma protein concentrations in 189 patients using Luminex technology and analyzed results.RESULTS:We identified baseline levels of apolipoprotein H (apoH) as a surrogate marker for sustained virological response (SVR). Notably, increased plasma concentration of apoH, used in combination with known clinical parameters, established a robust model with improved classification of patients as likely to achieve SVR (AUC = 0.77, Se = 66%, Sp = 72%, NRI = 39%). Moreover, we provide mechanistic information that indicates a previously unidentified role for apoH during viral entry. Using a human liver slices HCV infection model, we demonstrate that apoH limits replication.CONCLUSION:These data support testing of new biomarker strategies for the management of cirrhotic HCV patients and expand our understanding of how apoH may intersect with HCV infection
Published: 2015
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26. Frontal sinus revision rate after nasal polyposis surgery including frontal recess clearance and middle turbinectomy: A long-term analysis

Author: Pierre Bonfils, Ollivier Laccourreye, Hakim Benkhatar, Idir Khettab, and Philippe Sultanik
Subjects: Adult, Reoperation, medicine.medical_specialty, Sphenoid Sinus, medicine.medical_treatment, Turbinectomy, Nasal Surgical Procedures, Mucocele, Turbinates, 03 medical and health sciences, 0302 clinical medicine, Frontal Sinusitis, Nasal Polyps, Ethmoid Sinus, Ethmoid sinus, Risk Factors, medicine, Humans, Nasal polyps, Longitudinal Studies, 030223 otorhinolaryngology, Osteitis, Frontal sinus, business.industry, General Medicine, Functional endoscopic sinus surgery, Middle Aged, medicine.disease, Asthma, Surgery, medicine.anatomical_structure, Otorhinolaryngology, 030220 oncology & carcinogenesis, Frontal Sinus, business, Tomography, X-Ray Computed
Abstract: Objective To determine the frontal sinus revision rate after nasal polyposis (NP) surgery including frontal recess clearance (FRC) and middle turbinectomy (MT), to search for predictive factors and to analyse surgical management. Methods Longitudinal analysis of 153 patients who consecutively underwent bilateral sphenoethmoidectomy with FRC and MT for NP with a minimum follow-up of 7 years. Decision of revision surgery was made in case of medically refractory chronic frontal sinusitis or frontal mucocele. Univariate and multivariate analysis incorporating clinical and radiological variables were performed. Results The frontal sinus revision rate was 6.5% (10/153). The mean time between the initial procedure and revision surgery was 3 years, 10 months. Osteitis around the frontal sinus outflow tract (FSOT) was associated with a higher risk of frontal sinus revision surgery (p = 0.01). Asthma and aspirin intolerance did not increase the risk, as well as frontal sinus ostium diameter or residual frontoethmoid cells. Among revised patients, 60% required multiple procedures and 70% required frontal sinus ostium enlargement. Conclusions Our long-term study reports that NP surgery including FRC and MT is associated with a low frontal sinus revision rate (6.5%). Patients developing osteitis around the FSOT have a higher risk of frontal sinus revision surgery. As mucosal damage can lead to osteitis, FSOT mucosa should be preserved during initial NP surgery. However, as multiple procedures are common among NP patients requiring frontal sinus revision, frontal sinus ostium enlargement should be considered during first revision in the hope of reducing the need of further revisions.
Published: 2017

27. P: 65 Drug-induced Hyperammonaemia: Data From VigiBase, the WHO Database

Author: Philippe Sultanik, Dominique Thabut, Charlotte Bouzbib, Nicolas Weiss, Kevin Bihan, Bénédicte Lebrun-Vignes, Joe-Elie Salem, and Marika Rudler
Subjects: Drug, Hepatology, business.industry, media_common.quotation_subject, Gastroenterology, Medicine, Bioinformatics, business, media_common
Published: 2019
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28. Inhibition of DPP4 activity in humans establishes its in vivo role in CXCL10 post‐translational modification: prospective placebo‐controlled clinical studies

Author: Stanislas Pol, Grace Linder, Kristin V. Tarbell, Jérémie Decalf, Vincent Mallet, Matthew L. Albert, Armanda Casrouge, Estelle Mottez, Darragh Duffy, Jeffrey D. Price, Philippe Sultanik, Immunobiologie des Cellules Dendritiques, Institut Pasteur [Paris] - Institut National de la Santé et de la Recherche Médicale (INSERM), Diabetes Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Centre d'Immunologie Humaine (CIH), Service d'hépatologie médicale [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Cochin [AP-HP], Institut Pasteur [Paris], Department of Cancer Immunology, Genentech, Inc. [San Francisco], This work was supported by the Agence nationale de recherches sur le sida et les hépatites virales (ANRS) and the Ligue nationale contre le cancer and by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), National Institutes of Health [Bethesda] (NIH), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Vougny, Marie-Christine
Subjects: 0301 basic medicine, Chemokine, [SDV.IMM] Life Sciences [q-bio]/Immunology, Dipeptidyl Peptidase 4, [SDV]Life Sciences [q-bio], Lymphocyte, chemokines, Pharmacology, Biology, DPP4, Placebos, 03 medical and health sciences, 0302 clinical medicine, In vivo, Report, medicine, Humans, CXCL10, Prospective Studies, Pharmacology & Drug Discovery, post‐translational modifications, Dipeptidyl peptidase-4, Dipeptidyl-Peptidase IV Inhibitors, Sitagliptin Phosphate, Antagonist, Post-translational Modifications, Proteolysis & Proteomics, Hepatitis C, Chronic, clinical study, Healthy Volunteers, Microbiology, Virology & Host Pathogen Interaction, 3. Good health, Chemokine CXCL10, Clinical trial, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Sitagliptin, Proteolysis, Immunology, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Molecular Medicine, Protein Processing, Post-Translational, Reports, medicine.drug
Abstract: International audience; Biochemical experiments, animal models, and observational studies in humans all support a role of dipeptidyl peptidase 4 (DPP4) in the N-terminal truncation of CXCL10, which results in the generation of an antagonist form of the chemokine that limits T-cell and NK cell migration. Motivated by the ability to regulate lymphocyte trafficking in vivo, we conducted two prospective clinical trials to test the effects of DPP4 inhibition on CXCL10 processing in healthy donors and in chronic hepatitis C patients, a disease in which DPP4 levels are found to be elevated. Participants were treated daily with 100 mg sitagliptin, a clinically approved DPP4 inhibitor. Plasma samples were analyzed using an ultrasensitive single-molecule assay (Simoa) to distinguish the full-length CXCL101-77 from the NH2-truncated CXCL103-77, as compared to the total CXCL10 levels. Sitagliptin treatment resulted in a significant decrease in CXCL103-77 concentration, a reciprocal increase in CXCL101-77, with only minimal effects on total levels of the chemokine. These data provide the first direct evidence that in vivo DPP4 inhibition in humans can preserve the bioactive form of CXCL10, offering new therapeutic opportunities for DPP4 inhibitors.
Published: 2016
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29. The relationship between liver stiffness measurement and outcome in patients with chronic hepatitis C and cirrhosis: a retrospective longitudinal hospital study

Author: Marion Corouge, Hélène Fontaine, Laurence Bousquet, D. Soudan, Vincent Mallet, Philippe Sogni, L. Kramer, Anaïs Vallet-Pichard, Stanislas Pol, S. Bouam, Philippe Sultanik, J.-F. Meritet, and E. Boueyre
Subjects: Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, Gastroenterology, End Stage Liver Disease, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Pharmacology (medical), Longitudinal Studies, Prospective Studies, Prospective cohort study, Aged, Retrospective Studies, Hepatology, business.industry, Proportional hazards model, Retrospective cohort study, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, Surgery, Hospitalization, Treatment Outcome, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Disease Progression, Elasticity Imaging Techniques, 030211 gastroenterology & hepatology, Female, Metabolic syndrome, business
Abstract: SummaryBackground There is a relationship between liver stiffness measurement (LSM) and outcome of HCV patients. Aim To evaluate the performance of LSM to predict outcome of HCV patients at risk of liver-related complication. Methods We established a retrospective longitudinal cohort of 341 HCV patients with unequivocal cirrhosis. All underwent LSM and were followed from September 2006 to July 2015. Outcome measure was a composite end-point of end-stage liver disease (ESLD) and/or hepatocellular carcinoma (HCC). Cox models and areas under receiver operating characteristic (AUROC) curves were used to evaluate independent risk factors of outcome. Results Overall, LSM was below the 12.5 kPa threshold in 129 (37.8%) patients, including three-fourth and one-third of patients with or without a sustained virological response respectively. Liver disease progressed in 136 (39.9%) patients after a median observational period of 23.5 months. Older age, male gender, alcohol use disorders, metabolic syndrome and LSM were independent risk factors of liver disease progression. Age, alcohol use disorders and LSM were independently associated with ESLD. Age, gender and metabolic syndrome, but not LSM, were associated with HCC. The AUROC curves for disease progression, ESLD and HCC were 0.67, 0.70 and 0.58 respectively. Patients with a liver stiffness >12.5 kPa were at the highest risk of liver disease progression; below 12.5 kPa, liver stiffness was not discriminant. Conclusion Liver stiffness measurement is not a surrogate of disease progression of HCV patients with cirrhosis. HCV patients with cirrhosis should undergo the recommended follow-up, regardless of liver stiffness measurement.
Published: 2016

30. Mortality associated with the treatment of HCV with direct-acting antivirals

Author: Philippe Sogni, L. Kramer, Stanislas Pol, Philippe Sultanik, Anaïs Vallet-Pichard, and A Laurain
Subjects: medicine.medical_specialty, business.industry, Gastroenterology, Clinical settings, Hepatitis C, medicine.disease, DIRECT ACTING ANTIVIRALS, Tertiary care, Surgery, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Internal medicine, Cohort, medicine, 030211 gastroenterology & hepatology, 030212 general & internal medicine, business, Adverse effect, Hepatic decompensation
Abstract: We read with interest the study by Welzel et al 1 confirming the high efficacy of oral direct-acting antiviral agents (DAAs) for the treatment of chronic HCV infection.2 Results about safety are less clear, since in these patients who have a high risk of hepatic decompensation or death within 12 months, the rate of death was 7.8% during treatment and the 12 weeks post-treatment. These deaths and most safety events were associated with advanced liver disease and not considered treatment related. The largest phase III studies (COSMOS, ION1 and ION3, SAPPHIRE) did not report any death during DAA treatment and severe adverse events occurring during therapy were considered to be unlikely related to DAAs.3 In real-life clinical settings, mortality has been observed in around 0.5% (0.3% for the French ANRS CO22 HEPATHER cohort and 0.6% for the US TARGET cohort). In our tertiary care …
Published: 2017
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31. Bystander hyperactivation of preimmune CD8+ T cells in chronic HCV patients

Author: Tobias Flecken, Jeremy Boussier, Farhad Heshmati, Vincent Mallet, Marit M. van Buuren, Francesco Nicoli, Matthew L. Albert, Aurélie Schnuriger, Ton N. Schumacher, Philippe Sultanik, Laurence Bousquet, Elisabetta Bianchi, Robert Thimme, Annick Lim, A. Garbarg-Chenon, Darragh Duffy, Antoine Toubert, Kerstin Johnsson, Emmanuel Clave, Stanislas Pol, Estelle Mottez, Cécile Alanio, Brieuc Perot, Victor Appay, Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie Humaine (CIH), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Albert-Ludwigs-Universität Freiburg, Immunorégulation, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Département d'Immunologie - Department of Immunology, Institut Pasteur [Paris], Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Lund University [Lund], Université Paris Descartes - Paris 5 (UPD5), EFS [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 Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre d'Immunologie Humaine ( CIH ), Centre d'Immunologie et de Maladies Infectieuses ( CIMI ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Département d'Immunologie, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), Netherlands Cancer Institute ( NKI ), Laboratoire de virologie [CHU Trousseau], Université Paris Descartes - Paris 5 ( UPD5 ), CHU Cochin [AP-HP], and HAL UPMC, Gestionnaire
Subjects: chronic inflammation, medicine, Hepacivirus, CD8-Positive T-Lymphocytes, Lymphocyte Activation, TCR signaling, immunology, 0302 clinical medicine, CD8 T cell dysfunction, Receptors, Cytotoxic T cell, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Pre-immune repertoire, Biology (General), Chronic, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, General Neuroscience, human biology, General Medicine, Hepatitis C, 3. Good health, medicine.anatomical_structure, Antigen, [SDV.IMM]Life Sciences [q-bio]/Immunology, Research Article, Signal Transduction, [SDV.IMM] Life Sciences [q-bio]/Immunology, Naive T cell, viral immunology, QH301-705.5, T cell, Science, Receptors, Antigen, T-Cell, Biology, CD5 Antigens, General Biochemistry, Genetics and Molecular Biology, NO, 03 medical and health sciences, Immune system, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, human, Cross-Sectional Studies, Hepatitis C, Chronic, Humans, Human Biology and Medicine, 030304 developmental biology, General Immunology and Microbiology, T-cell receptor, T-Cell, Chronic infection, Immunology, CD5, CD8, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract: Chronic infection perturbs immune homeostasis. While prior studies have reported dysregulation of effector and memory cells, little is known about the effects on naïve T cell populations. We performed a cross-sectional study of chronic hepatitis C (cHCV) patients using tetramer-associated magnetic enrichment to study antigen-specific inexperienced CD8+ T cells (i.e., tumor or unrelated virus-specific populations in tumor-free and sero-negative individuals). cHCV showed normal precursor frequencies, but increased proportions of memory-phenotype inexperienced cells, as compared to healthy donors or cured HCV patients. These observations could be explained by low surface expression of CD5, a negative regulator of TCR signaling. Accordingly, we demonstrated TCR hyperactivation and generation of potent CD8+ T cell responses from the altered T cell repertoire of cHCV patients. In sum, we provide the first evidence that naïve CD8+ T cells are dysregulated during cHCV infection, and establish a new mechanism of immune perturbation secondary to chronic infection. DOI: http://dx.doi.org/10.7554/eLife.07916.001, eLife digest Long-lasting or “chronic” infections massively perturb the immune system as a way to favor their own growth. In particular, they can stop T cells – a subtype of immune cells that help to destroy viruses – from working well. For example, HIV and hepatitis C viruses can overwork T cells and cause them to die. This can make individuals vulnerable to other infections. In healthy people, T cells that have participated in the fight against particular infections continue to live to provide a memory of those past infections. Groups of “naïve” T cells that have not yet encountered an infected cell also patrol the body, ready to respond to infections by a new virus. There are relatively few virus-specific naïve T cells in the body, so until recently it has been hard to study them. As a result, researchers know little about how these cells are affected by long-lasting infections, and whether chronic infection affects our capacity to fight unrelated infections. Alanio et al. have now used a highly sensitive technique to compare naïve T cells found in the blood of three groups of people: those with chronic hepatitis C infections, those who have been cured of a chronic hepatitis C infection, and healthy people. This revealed that the naïve T cells are negatively affected by chronic hepatitis C infections, and become hypersensitive: they get easily overexcited, which can lead to their death. This compromises the immune defenses at the moment they are most needed. Closer inspection showed that the naïve T cells of patients with hepatitis C are hypersensitive because they have less of a protein called CD5 on their surface. This protein acts as a natural brake for the T cells, and thus having less results in the T cells mounting stronger immune responses. Although this might be beneficial when fighting certain infections, this may also account for conditions where T cells attack healthy tissues. Finally, Alanio et al. found evidence that people who have been cured of a chronic hepatitis C infection recover a healthy set of naïve T cells within two years. Treating patients as soon as an infection is diagnosed therefore has several benefits: as well as clearing the virus, this will reset the immune system balance and reduce the damage that hyperactive immune cells cause to the body. The results also have implications for vaccinations, which work by pushing naïve T cells to arm themselves against a particular virus. The discovery that naïve T cells are hypersensitive in patients with hepatitis C suggests that we may need a distinct strategy for efficiently vaccinating these patients. It is indeed possible that standard vaccines – tested in groups of healthy people – may result in unexpected and unwanted immune responses in individuals with hepatitis C. These open questions will be addressed in further studies. It will also be of interest to know if other chronic viruses have the same ability to alter the activity of naïve T cells. DOI: http://dx.doi.org/10.7554/eLife.07916.002
Published: 2015
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32. Baseline sensitivity of T cells to alpha-IFN correlates with sustained virological response to IFN-based triple therapy in HCV infection

Author: Christophe Hézode, Cécile Alanio, G. Uze, Armanda Casrouge, Vincent Mallet, I. Rosa-Hézode, P. Pellet, Estelle Mottez, Matthew L. Albert, Philippe Renard, Stanislas Pol, Philippe Sultanik, Laurence Bousquet, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunobiologie des Cellules Dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie Humaine (CIH), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Victor Dupouy, CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was supported by grants from the Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS 11416) and ERC Starting award (M.A.). We thank the Fondation pour la Recherche Médicale for master and PhD student bursaries, We thank the Fondation pour la Recherche Médicale for master and PhD student bursaries, the Etablissement Français du Sang (EFS) for healthy donors samples, S. Pellegrini for critical review, S. Feton and K. Sperber for coordination of the clinical protocol, J. Gaston, S. Lagaye and M. Andrieu for technical assistance. We would also like to acknowledge the Department of Development, Reproduction and Cancer, Institut Cochin, Paris, the Department of Immunology, Institut Cochin, Paris, and the Centre d'Immunologie Humaine (CIH), Institut Pasteur, Paris, for support and technical expertise, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Pitié-Salpêtrière [APHP], CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut Cochin (UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] - Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Montpellier 1 (UM1) - Université Montpellier 2 - Sciences et Techniques (UM2) - Université de Montpellier (UM) - Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Cochin [AP-HP]
Subjects: Male, MESH: T-Lymphocytes/metabolism, T-Lymphocytes, Drug Resistance, MESH: Hepatitis C, Chronic/virology, MESH: Leukocytes, Mononuclear/drug effects, Telaprevir, chemistry.chemical_compound, Pegylated interferon, Phosphorylation, MESH: Treatment Outcome, MESH: Aged, MESH: STAT1 Transcription Factor/metabolism, MESH: Middle Aged, biology, MESH: Polymorphism, Single Nucleotide, IFNα desensitization, IFN-based triple therapy, MESH: T-Lymphocytes/immunology, Middle Aged, Viral Load, MESH: Antiviral Agents/pharmacology, MESH: Interleukins/genetics, MESH: Case-Control Studies, 3. Good health, STAT1 Transcription Factor, Treatment Outcome, Infectious Diseases, MESH: Interferon-alpha/therapeutic use, [SDV.IMM]Life Sciences [q-bio]/Immunology, Drug Therapy, Combination, Female, MESH: Viral Load, medicine.drug, MESH: Leukocytes, Mononuclear/metabolism, MESH: Hepatitis C, Chronic/drug therapy, [SDV.IMM] Life Sciences [q-bio]/Immunology, CD3, MESH: T-Lymphocytes/drug effects, T cells, Alpha interferon, Antiviral Agents, Polymorphism, Single Nucleotide, Peripheral blood mononuclear cell, Virology, Boceprevir, medicine, Humans, Aged, MESH: Hepatitis C, Chronic/immunology, MESH: Humans, Hepatology, MESH: Phosphorylation, business.industry, Interleukins, Ribavirin, MESH: Drug Resistance/genetics, Interferon-alpha, Hepatitis C, Chronic, MESH: Male, MESH: Drug Therapy, Combination, MESH: Interferon-alpha/pharmacology, chemistry, MESH: Leukocytes, Mononuclear/immunology, Case-Control Studies, Immunology, MESH: Antiviral Agents/therapeutic use, Leukocytes, Mononuclear, biology.protein, chronic HCV infection, Interferons, business, MESH: Female, Ex vivo, MESH: Hepatitis C, Chronic/genetics
Abstract: International audience; Chronic infection with HCV is a public health problem with approximately 170 million people infected worldwide. Interferon alpha (IFNα) sensitivity in liver and IL28B genotype has been identified as important determinants of HCV clearance in the setting of pegylated interferon/ribavirin treatment. Herein, we explored IFNα sensitivity in PBMC from 21 healthy donors and 21 HCV-infected patients treated with pegylated interferon/ribavirin and HCV nonstructural protein-3 inhibitors (i.e. telaprevir/boceprevir). We explored phospho-STAT1 level as read-out for IFN signalling pathway activation in PBMC, T cells and monocytes and correlated results with virological response. We found that PBMC from healthy donors are desensitized to IFNα after priming and challenged with IFNα, with a subsequent decrease of phospho-STAT1 and interferon-stimulated genes. Furthermore, we show that CD3+ T cells, but not monocytes, become desensitized after 4 weeks of treatment, with a significant decrease of phospho-STAT1 after ex vivo IFNα stimulation. Finally, we identified baseline phospho-STAT1 level in CD3+ T cells as a potential biomarker of sustained virological response, regardless of the IL28B genotype. In the upcoming costly era of IFN-sparing regimen, baseline IFNα sensitivity could act as biomarker to define cost-effectiveness strategies of treatment by identifying patients who will or will not respond to IFN-based treatments.
Published: 2015
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33. Author response: Bystander hyperactivation of preimmune CD8+ T cells in chronic HCV patients

Author: Philippe Sultanik, Marit M. van Buuren, Elisabetta Bianchi, A. Garbarg-Chenon, Darragh Duffy, Robert Thimme, Matthew L. Albert, Jeremy Boussier, Annick Lim, Cécile Alanio, Aurélie Schnuriger, Farhad Heshmati, Antoine Toubert, Kerstin Johnsson, Ton N. Schumacher, Estelle Mottez, Francesco Nicoli, Laurence Bousquet, Vincent Mallet, Emmanuel Clave, Tobias Flecken, Stanislas Pol, Brieuc Perot, and Victor Appay
Subjects: Hyperactivation, business.industry, Immunology, Bystander effect, Cytotoxic T cell, Medicine, business
Published: 2015
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34. Patients with chronic hepatitis B should be screened for hepatocellular carcinoma regardless of liver stiffness measurement

Author: Philippe Sogni, Jean-François Meritet, Stanislas Pol, Philippe Sultanik, and Vincent Mallet
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Hepatology, business.industry, Liver Neoplasms, medicine.disease, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Text mining, Hepatitis B, Chronic, Chronic hepatitis, Liver stiffness, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Internal medicine, medicine, Elasticity Imaging Techniques, Humans, 030211 gastroenterology & hepatology, Female, business
Published: 2015

35. [Treatment of chronic hepatitis B virus infection and hepatocellular carcinoma prevention]

Author: Damien, Soudan, Philippe, Sultanik, and Stanislas, Pol
Subjects: Liver Cirrhosis, Risk, Carcinoma, Hepatocellular, Cross-Sectional Studies, Hepatitis B, Chronic, Carcinogenesis, Carrier State, Liver Neoplasms, Humans, Guideline Adherence, Interferons, Antiviral Agents
Abstract: Chronic hepatitis B virus (HBV) infection is a major public health problem. It concerns more than 240 million people over the world. Natural HBV history leads to hepatocellular carcinoma (HCC), developed on cirrhotic liver and/or by direct viral cacinogenesis. HCC incidence is estimated between 0,2 and 1% per year. The risk of HCC development showed a positive correlation with the level of HBV DNA in the sera. This virosuppression, obtained with interferon or analogs, can reduce the incidence of HCC development during chronic HBV infection. In case of HCC curative surgery, sustained virological response showed a protective effect on recurrence development. Guidelines suggest to treat every cirrhotic or highly replicative patients, and to screen every six months chronic HBs antigen carrier to prevent HCC development.
Published: 2015

36. Lengthy Follow-up After Liver Transplantation for Nodular Regenerative Hyperplasia in Human Immunodeficiency Virus–Infected Patients

Author: Philippe Sultanik, Jean-Charles Duclos-Vallée, Mylène Sebagh, Teresa Antonini, Elina Teicher, Didier Samuel, Audrey Coilly, and Bruno Roche
Subjects: Transplantation, Pathology, medicine.medical_specialty, medicine.diagnostic_test, business.industry, medicine.medical_treatment, Treatment outcome, Human immunodeficiency virus (HIV), Disease, Liver transplantation, medicine.disease_cause, medicine.disease, Biopsy, medicine, Graft survival, business, Nodular regenerative hyperplasia
Published: 2013
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37. Retreatment of Sofosbuvir-Including Regimen Failures in the Real Life

Author: E. Boueyre, Stanislas Pol, Anaïs Vallet-Pichard, Hélène Fontaine, Philippe Sogni, Arielle R. Rosenberg, Vincent Mallet, J.-F. Mertitet, L. Kramer, A Laurain, and Philippe Sultanik
Subjects: medicine.medical_specialty, Regimen, Hepatology, Sofosbuvir, business.industry, medicine, business, medicine.drug, Surgery
Published: 2016
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38. Relationship between Alcohol use Disorders and Response to Antiviral Treatment on the Prognosis of Cirrhotic Patients with Chronic Hepatitis C

Author: V. Thepot, Stanislas Pol, Marion Corouge, S. Bouam, Philippe Sultanik, Hélène Fontaine, Philippe Sogni, Vincent Mallet, B. Lavielle, L. Kramer, and Anaïs Vallet-Pichard
Subjects: medicine.medical_specialty, chemistry.chemical_compound, Hepatology, chemistry, Chronic hepatitis, business.industry, Internal medicine, medicine, Alcohol, Antiviral treatment, business, Gastroenterology
Published: 2016
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39. Non-Tumoral Portalvein Thrombosis and End-Stage Liver Disease in Patients with Cirrhosis: A Longitudinal Retrospective Cohort

Author: Hélène Fontaine, Vincent Mallet, Anaïs Vallet-Pichard, Philippe Sultanik, Stanislas Pol, Marion Corouge, S. Bouam, Philippe Sogni, and J. Roux
Subjects: medicine.medical_specialty, Cirrhosis, Hepatology, business.industry, Internal medicine, Medicine, Retrospective cohort study, End stage liver disease, In patient, business, medicine.disease, Thrombosis, Gastroenterology
Published: 2016
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40. Regression of an HCV-associated disseminated marginal zone lymphoma under IFN-free antiviral treatment

Author: Stanislas Pol, Philippe Brault, Vincent Mallet, Philippe Sultanik, and Caroline Klotz
Subjects: Hepatitis C virus, Immunology, Marginal zone lymphoma, Cell Biology, Hematology, Biology, medicine.disease_cause, medicine.disease, Marginal zone, Biochemistry, Ifn free, Virology, Antigenic stimulation, hemic and lymphatic diseases, medicine, Marginal zone B-cell lymphoma, Antiviral treatment, Intracellular
Abstract: To the editor: Hepatitis C virus (HCV) is prevalent in B-cell–associated lymphomas, including marginal zone and diffuse large B-cell lymphomas.[1][1] A stepwise model of lymphomagenesis induced by chronic antigenic stimulation and/or a direct pro-oncogenic effect of intracellular HCV proteins is
Published: 2015
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41. Brief communication: case reports of ribavirin treatment for chronic hepatitis E

Author: Philippe Sogni, Sophie Tesse, Catherine Chakvetadze, Elisabeth Nicand, Stanislas Pol, Luc Mouthon, Vincent Mallet, Philippe Sultanik, and Eric Thervet
Subjects: Adult, Male, Pediatrics, medicine.medical_specialty, viruses, Hepatitis C virus, Administration, Oral, Chronic liver disease, medicine.disease_cause, Antiviral Agents, Virus, chemistry.chemical_compound, Immunocompromised Host, Hepatitis E virus, Ribavirin, Internal Medicine, medicine, Humans, T-Lymphocytopenia, Idiopathic CD4-Positive, Hepatitis B virus, business.industry, General Medicine, Middle Aged, medicine.disease, Kidney Transplantation, Hepatitis E, chemistry, Immunology, Chronic Disease, Emerging infectious disease, Female, Viral disease, Pancreas Transplantation, business
Abstract: There is currently no accepted treatment of chronic hepatitis E virus (HEV) infection.To report 2 patients in whom ribavirin therapy seemed to alter the natural history of chronic HEV infection.Case reports.Hepatology unit of a tertiary care center in France.A kidney and pancreas transplant recipient and a patient with idiopathic CD4(+) T lymphocytopenia, both with biopsy-proven chronic HEV infection.Patients received oral ribavirin, 12 mg/kg of body weight daily for 12 weeks.Liver function tests, detection of HEV RNA (viremia and stool shedding) by reverse transcriptase polymerase chain reaction, and anti-HEV IgM and IgG antibodies.Both patients had normalized liver function test results after 2 weeks of treatment and cleared HEV after 4 weeks of treatment. Hepatitis E virus RNA remained undetectable in the serum and stools throughout follow-up (3 months and 2 months for the first and second patient, respectively). Side effects were considered mild.Given the relatively short follow-up, the achievement of HEV eradication could not be claimed.Ribavirin is a potentially effective treatment of HEV infection and should be evaluated in patients with chronic HEV infection.None.
Published: 2010

42. HIV-associated obliterative portopathy (HIV-OP) underlies cryptogenic liver disease in HIV-seropositive patients

Author: Vincent Mallet, Anaïs Vallet-Pichard, Philippe Sultanik, and Stanislas Pol
Subjects: Hiv seropositive, business.industry, Liver Diseases, Health Policy, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, medicine.disease, Radiography, Liver disease, Infectious Diseases, Immunology, medicine, Humans, Pharmacology (medical), business
Published: 2010
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43. The Relationship between FIB-4 Index Variations and Outcome in Patients with Chronic Hepatitis C and Cirrhosis: Comparison with Liver Stiffness Measurement

Author: Hélène Fontaine, Philippe Sultanik, Stanislas Pol, Vincent Mallet, S. Bouam, Jean-François Meritet, Anaïs Vallet-Pichard, A Laurain, Marion Corouge, and Philippe Sogni
Subjects: medicine.medical_specialty, Cirrhosis, Hepatology, business.industry, Fib 4 index, medicine.disease, Gastroenterology, Surgery, Chronic hepatitis, Liver stiffness, Internal medicine, medicine, In patient, business
Published: 2016
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44. 1177 BASELINE Phospho-Stat1 LEVEL IN PBMC IS A NON-INVASIVE BIOMARKER OF EARLY VIROLOGICAL RESPONSE TO TRIPLE THERAPY IN CHRONIC HCV INFECTION – ANRS C10–08 STUDY

Author: Stanislas Pol, Matthew L. Albert, Philippe Sultanik, Armanda Casrouge, Laurence Bousquet, K. Sperber, C. Br'echot-Alanio, Estelle Mottez, Vincent Mallet, S. Feton, and Dalila Amroun
Subjects: Virological response, Oncology, medicine.medical_specialty, Hepatology, biology, business.industry, Internal medicine, Non invasive biomarkers, biology.protein, medicine, STAT1, business, Peripheral blood mononuclear cell
Published: 2013
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45. 1429 BASELINE APOLIPOPROTEIN H (ApoH) IS A PREDICTOR OF EARLY VIROLOGIC RESPONSE TO TRIPLE THERAPY (ANRS CO20-CUPIC)

Author: Arnaud Fontanet, Stanislas Pol, Vincent Mallet, C. Dorival-Mouly, Jean-Pierre Bronowicki, Christophe Hézode, Fabrice Carrat, Ioannis Theodorou, Armanda Casrouge, Laurent Abel, Yoann Barthe, Matthew L. Albert, H. Fonaine, E. Gayat, Estelle Mottez, and Philippe Sultanik
Subjects: medicine.medical_specialty, Hepatology, business.industry, Virologic response, Internal medicine, medicine, Baseline (configuration management), business, Gastroenterology, Apolipoprotein H
Published: 2013
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46. 824 BASELINE AND IN-TREATMENT BIOMARKERS FOR RESPONSE TO INTERFERON-BASED THERAPY IN CHRONIC HEPATITIS C

Author: Matthew L. Albert, Vincent Mallet, Philippe Sultanik, Armanda Casrouge, and Stanislas Pol
Subjects: medicine.medical_specialty, Hepatology, Chronic hepatitis, Interferon, business.industry, Internal medicine, medicine, Baseline (configuration management), business, Gastroenterology, medicine.drug
Published: 2012
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47. Liver fibrosis and all‐cause mortality in chronic HCV‐infected diabetic patients: A paradoxical association? (ANRS CO22 HEPATHER)

Author: Tangui, Barré, Clémence, Ramier, Vincent, Di Beo, Fabrice, Carrat, Hélène, Fontaine, Fabienne, Marcellin, Patrizia, Carrieri, Stanislas, Pol, Camelia, Protopopescu, Marie-Josée, Lafrance, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-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), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunité Innée - Innate Immunity, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), ANRS/AFEF Hepather study group: Delphine Bonnet, Virginie Sicart, François Bailly, Marjolaine Beaudoin, Dominique Giboz, Kerstin Hartig-Lavie, Marianne Maynard, Morane Cavellec, Marjorie Cheraud-Carpentier, François Raffi, Florian Vivrel, Jaouad Benhida, Jérôme Boursier, Paul Calès, Françoise Lunel, Frédéric Oberti, Nathalie Boyer, Audrey Gilibert, Nathalie Giuily, Giovanna Scoazec, Sandrine Fernandes, Sylvie Keser, Philippe Sultanik, Anaïs Vallet-Pichard, Juliette Foucher, Jean-Baptiste Hiriart, Aurore Mathias, Julien Vergniol, Chrystelle Ansaldi, 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, Nathalie Ganne-Carrié, Véronique Grando-Lemaire, Pierre Nahon, Alan Peltier, Judith Ung, Mariette Gougeon, Anne Guillygomarch, Caroline Jezequel, Romain Moirand, Thomas F Baumert, Michel Dofföel, Catherine Mutter, Pauline Simo-Noumbissie, Hélène Barraud, Mouni Bensenane, Abdelbasset Nani, Sarah Hassani-Nani, Marie-Albertine Bernard, Michael Bismuth, Ludovic Caillo, Stéphanie Faure, Georges-Philippe Pageaux, Marie P Ripault, Karl Barange, Christophe Bureau, Jean M Peron, Marie A Robic, Léa Tarallo, Marine Faure, Bruno Froissart, Marie-Noelle Hilleret, Vincent Leroy, 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 D Vallée, Mariagrazia Tateo, Armand Abergel, 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, Florent Artu, Valérie Canva, Sébastien Dharancy, Alexandre Louvet, Marc Bardou, Donya Da Costa Souhiel, Patrick Hillon, Marianne Latournerie, Yannick Bacq, Didier Barbereau, Charlotte Nicolas, Nisserine B Amara, Danièle Botta-Fridlund, Isabelle Portal, Moana Gelu-Simeon, Marie-Josée Lafrance, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), The cohort received financial support from the INSERM-ANRS (France Recherche Nord and Sud Sida-HIV Hépatites), the French ANR (Agence Nationale de la Recherche), the French DGS (Direction Générale de la Santé), Merck Sharp and Dohme, Janssen-Cilag, Gilead, Abbvie, Bristol-Myers Squibb and Roche. FC reports grants from INSERM-ANRS, during the conduct of the study, and personal fees from Imaxio, outside the submitted work. MB reports grants and personal fees from AbbVie and Gilead, outside the submitted work, and personal fees from MSD, Janssen, Boehringher Ingelheim, Intercept and Bristol-Myers Squibb, outside the submitted work. SP has received consulting and lecturing fees from Bristol-Myers Squibb, Janssen, Gilead, Roche, MSD, MYR-Pharma, Shionogi, Biotest and Abbvie, as well as grants from Bristol-Myers Squibb, Gilead, Roche and MSD. HF reports personal fees and invitations for medical meetings from Gilead, AbbVie, Bristol-Myers Squibb, MSD and Janssen, outside the submitted work. Other authors declare no financial support., and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Liver Cirrhosis, 0303 health sciences, medicine.medical_specialty, Hepatology, business.industry, Liver fibrosis, [SDV]Life Sciences [q-bio], Hepatitis C, Chronic, Antiviral Agents, Gastroenterology, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Text mining, Internal medicine, Diabetes Mellitus, medicine, Humans, 030211 gastroenterology & hepatology, business, All cause mortality, ComputingMilieux_MISCELLANEOUS, Follow-Up Studies, 030304 developmental biology
Abstract: International audience; No abstract available
Published: 2021
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48. Effectiveness of direct‐acting antivirals for chronic hepatitis C treatment in migrant and non‐migrant populations in France

Author: Mélanie Simony, Stanislas Pol, Elisabeth Delarocque-Astagneau, Hélène Fontaine, Fabrice Carrat, Tchadine Djaogol, Maël Baudoin, Fabienne Marcellin, Patrizia Carrieri, Ventzislava Petrov-Sanchez, Marc Bourlière, Camelia Protopopescu, Céline Dorival, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunobiologie des Cellules Dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Recherches fondamentales, cliniques et thérapeutiques sur les hépatites virales [Paris] (ANRS), ANRS France Recherche Nord & sud Sida-hiv hépatites, Hôpital Saint-Joseph [Marseille], Biostatistique, Biomathématique, Pharmacoépidémiologie et Maladies Infectieuses (B2PHI), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris]-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), The cohort received financial support from INSERM-ANRS (France Recherche Nord & Sud Sida-HIV Hépatites), the French ANR (Agence Nationale de la Recherche), the French DGS (Direction Générale de la Santé), Merck Sharp and Dohme, Janssen-Cilag, Gilead, Abbvie, Bristol-Myers Squibb and Roche., ANRS CO22 Hepather study group, ANRS-AFEF HEPATHER STUDY GROUP: Delphine Bonnet, Virginie Sicart (CHU Purpan, Toulouse, France), François Bailly, Marjolaine Beaudoin, Dominique Giboz, Kerstin Hartig-Lavie, Marianne Maynard(Hospices Civils de Lyon, Lyon, France), Morane Cavellec, Marjorie Cheraud-Carpentier, François Raffi, Florian Vivrel (Hôpital Hôtel-Dieu, Nantes, France), Jaouad Benhida, Jérôme Boursier, Paul Calès, Françoise Lunel, Frédéric Oberti (CHU Angers, Angers, France), Nathalie Boyer, Audrey Gilibert, Nathalie Giuily (Hôpital Beaujon, Clichy, France), Giovanna Scoazec (Hôpital Beaujon, Clichy, France and Hôpital Henri Mondor, Créteil, France), Sandrine Fernandes, Sylvie Keser, Philippe Sultanik, Anaïs Vallet-Pichard (Hôpital Cochin, Paris, France), Juliette Foucher, Jean-Baptiste Hiriart, Aurore Mathias, Julien Vergniol (Hôpital Haut-Lévêque, Pessac, Bordeaux, France), Chrystelle Ansaldi, Laëtitia Chouquet, Emilie De Luca, Valérie Oules (Hôpital Saint Joseph, Marseille, France), Rodolphe Anty, Eve Gelsi, Régine Truchi (CHU de Nice, Nice, France), Elena Luckina, Nadia Messaoudi, Joseph Moussali, (Groupe Hospitalier Pitié-Salpétrière, Paris, France), Barbara De Dieuleveult, Damien Labarriere, Pascal Poter, Si Nafa Si Ahmed (CHR La Source, Orléans, France), Nathalie Ganne-Carrié, Véronique Grando-Lemaire, Pierre Nahon, Alan Peltier, Judith Ung (Hôpital Jean Verdier, Bondy, France), Mariette Gougeon, Anne Guillygomarch, Caroline Jezequel (CHU Rennes, Rennes, France), Romain Moirand, Thomas F. Baumert, Michel Dofföel, Catherine Mutter, Pauline Simo-Noumbissie (Hôpitaux Universitaires de Strasbourg, Strasbourg, France), Hélène Barraud, Mouni Bensenane, Abdelbasset Nani, Sarah Hassani-Nani (CHU de Nancy, Vandoeuvre-lès-Nancy, France), Marie-Albertine Bernard (CHU de Nancy, Vandoeuvre-lès-Nancy, France and Centre Hospitalier Régional, Metz, France), Michael Bismuth, Ludovic Caillo, Stéphanie Faure, Georges-Philippe Pageaux, Marie Pierre Ripault (Hôpital Saint Eloi, Montpellier, France), Karl Barange, Christophe Bureau, Jean Marie Peron, Marie Angèle Robic, Léa Tarallo (CHU Purpan, Toulouse, France), Marine Faure, Bruno Froissart, Marie-Noelle Hilleret, Vincent Leroy (CHU de Grenoble, Grenoble, France), Odile Goria, Victorien Grard, Hélène Montialoux (CHU Charles Nicolle, Rouen, France), Muriel François, Christian Ouedraogo, Christelle Pauleau, Anne Varault (Hôpital Henri Mondor, Créteil, France), Tony Andreani, Bénédicte Angoulevant, Azeline Chevance, Lawrence Serfaty (Hôpital Saint-Antoine, Paris, France), Teresa Antonini, Audrey Coilly, Jean-Charles Duclos Vallée, Mariagrazia Tateo (Hôpital Paul Brousse, Villejuif, France), Armand Abergel, Corinne Bonny, Chanteranne Brigitte, Géraldine Lamblin, Léon Muti (Hôpital Estaing, Clermont-Ferrand, France), Abdenour Babouri, Virginie Filipe (Centre Hospitalier Régional, Metz, France), Camille Barrault, Laurent Costes, Hervé Hagège, Soraya Merbah (Centre Hospitalier Intercommunal, Créteil, France), Paul Carrier, Maryline Debette-Gratien, Jérémie Jacques (CHU Limoges, Limoges, France), Florent Artu, Valérie Canva, Sébastien Dharancy, Alexandre Louvet (CHRU Claude Huriez, Lille, France), Marc Bardou, Donya Da Costa Souhiel, Patrick Hillon, Marianne Latournerie (Dijon University Hospital, Dijon, France), Yannick Bacq, Didier Barbereau, Charlotte Nicolas (CHU Trousseau, 37 044 Tours, France), Nisserine Ben Amara, Danièle Botta-Fridlund, Isabelle Portal (CHU Timone, Marseille, France), Moana Gelu-Simeon and Marie-Josée Lafrance (CHU de Pointe-à-Pitre, Pointe-à-Pitre, Guadeloupe)., Université Paris Descartes - Paris 5 (UPD5), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, [SDV]Life Sciences [q-bio], Hepacivirus, Antiviral Agents, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Central Asia, Chronic hepatitis, Interquartile range, medicine, Humans, Prospective Studies, Poisson regression, Prospective cohort study, Socioeconomic status, direct-acting antivirals, Aged, Transients and Migrants, Hepatology, business.industry, virus diseases, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, 3. Good health, migrant, Cross-Sectional Studies, vulnerable population, 030220 oncology & carcinogenesis, symbols, Population study, population characteristics, 030211 gastroenterology & hepatology, France, hepatitis C, sustained virological response, business, Social vulnerability, Demography
Abstract: International audience; Despite universal health coverage in France, migrants face specific socioeconomic barriers that increase the likelihood of a suboptimal cascade of care for chronic hepatitis C virus (HCV) infection and impaired treatment effectiveness in this sub-population. We selected data collected from 2012 to 2018 from the ANRS CO22 HEPATHER prospective cohort study for chronic HCV participants with available data on treatment failure (defined as the presence of a detectable HCV-RNA load 12 weeks after their first DAA treatment ended). We performed multivariable Poisson regression models to test whether treatment failure rates differed significantly between HCV-infected migrants and non-migrants receiving DAA in France (cross-sectional analysis), while taking into account the former's world region of birth and other potential social vulnerability factors. Among the study population's 7,879 patients, 5,829 (74%) were non-migrants and 2,050 (26%) migrants. Median [interquartile range] age was 57 [51-65] years, 4433 (56%) were men and 369 (5%) of the entire study population had treatment failure. After multivariable adjustment, only migrants from Central Asia were at higher risk of treatment failure than non-migrants (aIRR = 2.83; 95% CI [1.72, 4.65]). Results from this large-scale study performed in France suggest a higher risk of DAA treatment failure in migrants from Central Asia than in non-migrants and confirm the overall low treatment failure rate in chronic HCV patients treated with DAA (whether migrants or not). Simplified models of care taking into account language and cultural barriers are needed to improve DAA effectiveness in migrants from Central Asia.
Published: 2021
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49. Cannabis use is associated with a lower risk of diabetes in chronic hepatitis C-infected patients (ANRS CO22 Hepather cohort)

Author: Barré, Tangui, Nishimwe, Marie Libérée, Protopopescu, Camelia, Marcellin, Fabienne, Carrat, Fabrice, Dorival, Céline, Delarocque-Astagneau, Elisabeth, Larrey, Dominique G., Bourlière, Marc, Petrov-Sanchez, Ventzislava, Simony, Mélanie, Pol, Stanislas, Fontaine, Hélène, Carrieri, Patrizia Maria, Pageaux, Georges Philippe, HAL UVSQ, Équipe, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), 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), Biostatistique, Biomathématique, Pharmacoépidémiologie et Maladies Infectieuses (B2PHI), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), 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), Merck Sharp and Dohme, MSD Agence Nationale de la Recherche, ANR AbbVie Bristol-Myers Squibb, BMS AbbVie Association Française pour l'Etude du Foie, AFEF Roche Gilead Sciences Shionogi Cilag MSD France, FC reports grants from INSERM-ANRS, during the conduct of the study, and personal fees from Imaxio, outside the submitted work. MB reports grants and personal fees from AbbVie and Gilead, outside the submitted work, and personal fees from MSD, Janssen, Boehringher Ingelheim, Intercept, and Bristol-Myers Squibb, outside the submitted work. SP has received consulting and lecturing fees from Bristol-Myers Squibb, Janssen, Gilead, Roche, MSD, MYR-Pharma, Shionogi, Biotest and Abbvie, as well as grants from Bristol-Myers Squibb, Gilead, Roche and MSD. HF reports personal fees and invitations for medical meetings from Gilead, AbbVie, Bristol-Myers Squibb, MSD, and Janssen, outside the submitted work. Other authors declare no financial support. The cohort received financial support from the INSERM-ANRS (France Recherche Nord & Sud Sida-HIV H?patites), the French ANR (Agence Nationale de la Recherche), the French DGS (Direction Générale de la Santé), Merck Sharp and Dohme, Janssen-Cilag, Gilead, Abbvie, Bristol-Myers Squibb, and Roche. Those funding sources had no role in the writing of the manuscript or the decision to submit it for publication. We thank the study participants and the participating clinicians at each site. We also thank the INSERM-ANRS for sponsoring, funding and conducting the ANRS CO22 Hepather cohort in collaboration with the French Association for the Study of the Liver (Association Fran?aise pour l'Etude du Foie: AFEF). Finally, our thanks to Jude Sweeney for the English revision and editing of our manuscript., On behalf of the ANRS/AFEF Hepather study group : Delphine Bonnet, Virginie Sicart (CHU Purpan, Toulouse, France), François Bailly, Marjolaine Beaudoin, Dominique Giboz, Kerstin Hartig‐Lavie, Marianne Maynard (Hospices Civils de Lyon, Lyon, France), Morane Cavellec, Marjorie Cheraud‐Carpentier, François Raffi, Florian Vivrel (Hôpital Hôtel‐Dieu, Nantes, France), Jaouad Benhida, Jérôme Boursier, Paul Calès, Françoise Lunel, Frédéric Oberti (CHU Angers, Angers, France), Nathalie Boyer, Audrey Gilibert, Nathalie Giuily (Hôpital Beaujon, Clichy, France), Giovanna Scoazec (Hôpital Beaujon, Clichy, France and Hôpital Henri Mondor, Créteil, France), Sandrine Fernandes, Sylvie Keser, Philippe Sultanik, Anaïs Vallet‐Pichard (Hôpital Cochin, Paris, France), Juliette Foucher, Jean‐Baptiste Hiriart, Aurore Mathias, Julien Vergniol (Hôpital Haut‐Lévêque, Pessac, Bordeaux, France), Chrystelle Ansaldi, Laëtitia Chouquet, Emilie De Luca, Valérie Oules (Hôpital Saint Joseph, Marseille, France), Rodolphe Anty, Eve Gelsi, Régine Truchi (CHU de Nice, Nice, France), Elena Luckina, Nadia Messaoudi, Joseph Moussali, (Groupe Hospitalier Pitié‐Salpétrière, Paris, France), Barbara De Dieuleveult, Damien Labarriere, Pascal Poter, Si Nafa Si Ahmed (CHR La Source, Orléans, France), Nathalie Ganne‐Carrié, Véronique Grando‐Lemaire, Pierre Nahon, Alan Peltier, Judith Ung (Hôpital Jean Verdier, Bondy, France), Mariette Gougeon, Anne Guillygomarch, Caroline Jezequel (CHU Rennes, Rennes, France), Romain Moirand, Thomas F. Baumert, Michel Dofföel, Catherine Mutter, Pauline Simo‐Noumbissie (Hôpitaux Universitaires de Strasbourg, Strasbourg, France), Hélène Barraud, Mouni Bensenane, Abdelbasset Nani, Sarah Hassani‐Nani (CHU de Nancy, Vandoeuvre‐lès‐Nancy, France), Marie‐Albertine Bernard (CHU de Nancy, Vandoeuvre‐lès‐Nancy, France and Centre Hospitalier Régional, Metz, France), Michael Bismuth, Ludovic Caillo, Stéphanie Faure, Georges‐Philippe Pageaux, Marie Pierre Ripault (Hôpital Saint Eloi, Montpellier, France), Karl Barange, Christophe Bureau, Jean Marie Peron, Marie Angèle Robic, Léa Tarallo (CHU Purpan, Toulouse, France), Marine Faure, Bruno Froissart, Marie‐Noelle Hilleret, Vincent Leroy (CHU de Grenoble, Grenoble, France), Odile Goria, Victorien Grard, Hélène Montialoux (CHU Charles Nicolle, Rouen, France), Muriel François, Christian Ouedraogo, Christelle Pauleau, Anne Varault (Hôpital Henri Mondor, Créteil, France), Tony Andreani, Bénédicte Angoulevant, Azeline Chevance, Lawrence Serfaty (Hôpital Saint‐Antoine, Paris, France), Teresa Antonini, Audrey Coilly, Jean‐Charles Duclos Vallée, Mariagrazia Tateo (Hôpital Paul Brousse, Villejuif, France), Armand Abergel, Corinne Bonny, Chanteranne Brigitte, Géraldine Lamblin, Léon Muti (Hôpital Estaing, Clermont‐Ferrand, France), Abdenour Babouri, Virginie Filipe (Centre Hospitalier Régional, Metz, France), Camille Barrault, Laurent Costes, Hervé Hagège, Soraya Merbah (Centre Hospitalier Intercommunal, Créteil, France), Paul Carrier, Maryline Debette‐Gratien, Jérémie Jacques (CHU Limoges, Limoges, France), Florent Artu, Valérie Canva, Sébastien Dharancy, Alexandre Louvet (CHRU Claude Huriez, Lille, France), Marc Bardou, Donya Da Costa Souhiel, Patrick Hillon, Marianne Latournerie (Dijon University Hospital, Dijon, France), Yannick Bacq, Didier Barbereau, Charlotte Nicolas (CHU Trousseau, 37044 Tours, France), Nisserine Ben Amara, Danièle Botta‐Fridlund, Isabelle Portal (CHU Timone, Marseille, France), Moana Gelu‐Simeon, Marie‐Josée Lafrance (CHU de Pointe‐à‐Pitre, Pointe‐à‐Pitre, Guadeloupe)., Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Eloi, 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)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: Liver Cirrhosis, cannabis, medicine.medical_specialty, Population, HIV Infections, 030209 endocrinology & metabolism, marijuana smoking, Lower risk, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Diabetes mellitus, Internal medicine, medicine, Humans, Risk factor, education, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, education.field_of_study, Hepatology, biology, business.industry, 1. No poverty, Hepatitis C, Hepatitis C, Chronic, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, biology.organism_classification, 3. Good health, chronic, Cross-Sectional Studies, Infectious Diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cohort, diabetes mellitus, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 030211 gastroenterology & hepatology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Cannabis, France, business
Abstract: International audience; Chronic hepatitis C virus (HCV) infection is a risk factor of insulin resistance, and HCV-infected patients are at a high risk of developing diabetes. In the general population, research has shown the potential benefit of cannabis use for the prevention of diabetes and related metabolic disorders. We aimed to test whether cannabis use is associated with a lower risk of diabetes in chronic HCV-infected patients. Chronic HCV-infected patients (n = 10 445) were selected from the French national, multicenter, observational ANRS CO22 Hepather cohort. Cross-sectional data collected at cohort enrollment were used to assess the association between patients’ clinical and behavioural characteristics and the risk of diabetes. Logistic regression model was performed with cannabis use as the main independent variable and a significance level set at 5%. A similar model stratified by the presence of advanced liver fibrosis (FIB-4 > 3.25) was also run. After multivariable adjustment, current (AOR [95%CI]: 0.49 [0.38-0.63]) and former (0.81 [0.67-0.98], P
Published: 2020
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50. The gamma-glutamyl transpeptidase to platelet ratio (GPR) predicts significant liver fibrosis and cirrhosis in patients with chronic HBV infection in West Africa

Author: Muriel Vray, Shevanthi Nayagam, Robert D. Goldin, Umberto D'Alessandro, Jo Lloyd, Ramou Njie, Yusuke Shimakawa, Penda Suso, Mark Thursz, Vincent Mallet, Makie Taal, Graham S Cooke, Gibril Ndow, Mustapha Khalil, Maud Lemoine, Harr-Freeya Njai, Papa Saliou Mbaye, Medical Research Council Unit The Gambia (MRC), Imperial College London, Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Edward Francis Small Teaching Hospital [Banjul, Gambia] (EFSTH), Ministry of Health and Social Welfare [Banjul, The Gambia] (MOHSW), Hôpital Principal de Dakar, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris], Université Paris Descartes - Paris 5 (UPD5), The study in The Gambia is part of the PROLIFICA programme funded by the European commission: EC FP7, P34114. The study in Senegal was funded by the ANRS (National Institute of Research on AIDS and Viral Hepatitis), France., The authors thank the MRC laboratories The Gambia unit, the local ministry of health and social welfare for supporting the project, all the study participants, the PROLIFICA team: in particular Ignatius Baldeh, Famara Bojang, Amie Ceesay, Mavis Foster-Nyarko, Debbo Jallow, Abdulie Jatta, Adam Jeng, Sheriff Kolley, Yamundow Jallow Samba, Alagie Sanneh, Bakary, Sanneh, Demba Sonko, Lamin Bojang, Saydiba Tamba and Debbie Garside, the project manager of the PROLIFICA programme. The authors also thank Professor Dominique Valla for his precious recommendations on haemostatic precautions before liver biopsy in the local resource-constrained setting. The authors also thank Dr Philippe Sultanik for his contributions to statistical analysis and Dr Patrick Ingiliz for his constructive comments and suggestions., European Project: 265994,EC:FP7:HEALTH,FP7-AFRICA-2010,PROLIFICA(2011), Institut Pasteur [Paris] (IP)-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)-Institut Pasteur [Paris] (IP)-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), Institut Pasteur [Paris] (IP), Imperial College Healthcare NHS Trust- BRC Funding, Commission of the European Communities, and Medical Research Council (MRC)
Subjects: Liver Cirrhosis, Male, Pathology, Cirrhosis, MESH: Biomarkers / blood, Biopsy, Gastroenterology, Severity of Illness Index, MESH: Biopsy, 0302 clinical medicine, Fibrosis, SIMPLE NONINVASIVE INDEX, FIBROSIS, Gamma-glutamyltransferase, MESH: Hepatitis B, Chronic* / complications, MESH: Middle Aged, biology, medicine.diagnostic_test, TRANSIENT ELASTOGRAPHY, gamma-Glutamyltransferase, Hepatitis B, Middle Aged, FIBROTEST, MESH: Liver Cirrhosis* / etiology, MESH: Predictive Value of Tests, 3. Good health, MESH: Biomarkers / analysis, Africa, Western, MESH: Hepatitis B, Chronic* / pathology, Liver, Dimensional Measurement Accuracy, 030220 oncology & carcinogenesis, Predictive value of tests, Liver biopsy, Area Under Curve, HEPATITIS B, 030211 gastroenterology & hepatology, Female, Life Sciences & Biomedicine, CHRONIC HEPATITIS-B, Adult, medicine.medical_specialty, AMINOTRANSFERASE, BIOMARKERS, STIFFNESS MEASUREMENT, MESH: Africa, Western / epidemiology, MESH: Liver / pathology, 03 medical and health sciences, Hepatitis B, Chronic, MESH: gamma-Glutamyltransferase* / blood, Predictive Value of Tests, MESH: Liver Cirrhosis* / diagnosis, Internal medicine, MESH: Severity of Illness Index, medicine, Humans, DIAGNOSTIC-ACCURACY, MESH: Patient Acuity, MESH: Platelet Count / methods, Science & Technology, MESH: Humans, Gastroenterology & Hepatology, business.industry, FibroTest, Platelet Count, Patient Acuity, 1103 Clinical Sciences, MESH: Adult, MESH: Hepatitis B, Chronic* / diagnosis, medicine.disease, MESH: Male, MARKER, MESH: Liver Cirrhosis* / pathology, biology.protein, 1114 Paediatrics and Reproductive Medicine, MESH: Area Under Curve, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, VIRAL-HEPATITIS, MESH: Dimensional Measurement Accuracy, Transient elastography, business, MESH: Female, MESH: gamma-Glutamyltransferase* / analysis
Abstract: International audience; Background: Simple and inexpensive non-invasive fibrosis tests are highly needed but have been poorly studied in sub-Saharan Africa.Methods: Using liver histology as a gold standard, we developed a novel index using routine laboratory tests to predict significant fibrosis in patients with chronic HBV infection in The Gambia, West Africa. We prospectively assessed the diagnostic accuracy of the novel index, Fibroscan, aspartate transaminase-to-platelet ratio index (APRI), and Fib-4 in Gambian patients with CHB (training set) and also in French and Senegalese CHB cohorts (validation sets).Results: Of 135 consecutive treatment-naïve patients with CHB who had liver biopsy, 39% had significant fibrosis (Metavir fibrosis stage ≥F2) and 15% had cirrhosis (F4). In multivariable analysis, gamma-glutamyl transpeptidase (GGT) and platelet count were independent predictors of significant fibrosis. Consequently, GGT-to-platelet ratio (GPR) was developed. In The Gambia, the area under the receiver operating characteristic curve (AUROC) of the GPR was significantly higher than that of APRI and Fib-4 to predict ≥F2, ≥F3 and F4. In Senegal, the AUROC of GPR was significantly better than Fib-4 and APRI for ≥F2 (0.73, 95% CI 0.59 to 0.86) and better than Fib-4 and Fibroscan for ≥F3 (0.93, 0.87 to 0.99). In France, the AUROC of GPR to diagnose ≥F2 (0.72, 95% CI 0.59 to 0.85) and F4 (0.87, 0.76 to 0.98) was equivalent to that of APRI and Fib-4.Conclusions: The GPR is a more accurate routine laboratory marker than APRI and Fib-4 to stage liver fibrosis in patients with CHB in West Africa. The GPR represents a simple and inexpensive alternative to liver biopsy and Fibroscan in sub-Saharan Africa.
Published: 2016
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