Publications by authors named "Stanislas Pol"

373 Publications

Differential levels of IFNα subtypes in autoimmunity and viral infection.

Cytokine 2021 Apr 30:155533. Epub 2021 Apr 30.

Translational Immunology Lab, Institut Pasteur, Paris, France. Electronic address:

Type I interferons are essential for host response to viral infections, while dysregulation of their response can result in autoinflammation or autoimmunity. Among IFNα (alpha) responses, 13 subtypes exist that signal through the same receptor, but have been reported to have different effector functions. However, the lack of available tools for discriminating these closely related subtypes, in particular at the protein level, has restricted the study of their differential roles in disease. We developed a digital ELISA with specificity and high sensitivity for the IFNα2 subtype. Application of this assay, in parallel with our previously described pan-IFNα assay, allowed us to study different IFNα protein responses following cellular stimulation and in diverse patient cohorts. We observed different ratios of IFNα protein responses between viral infection and autoimmune patients. This analysis also revealed a small percentage of autoimmune patients with high IFNα2 protein measurements but low pan-IFNα measurements. Correlation with an ISG score and functional activity showed that in this small sub group of patients, IFNα2 protein measurements did not reflect its biological activity. This unusual phenotype was partly explained by the presence of anti-IFNα auto-antibodies in a subset of autoimmune patients. This study reports ultrasensitive assays for the study of IFNα proteins in patient samples and highlights the insights that can be obtained from the use of multiple phenotypic readouts in translational and clinical studies.
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http://dx.doi.org/10.1016/j.cyto.2021.155533DOI Listing
April 2021

Predictive Factors for Hepatocellular Carcinoma in Chronic Hepatitis B Using Structural Equation Modeling: A Prospective Cohort Study.

Clin Res Hepatol Gastroenterol 2021 Apr 27:101713. Epub 2021 Apr 27.

Digestive Center, Centre Hospitalier Universitaire de Nice, INSERM U1065-8, Nice, France.

Background & Aims: The factors predicting hepatocellular carcinoma (HCC) occurrence in chronic hepatitis B need to be precisely known to improve its detection. We identified pathways and individual predictive factors associated with HCC in the ANRS CO22 HEPATHER cohort.

Methods: The study analyzed HBV-infected patients recruited at 32 French expert hepatology centers from August 6, 2012, to December 31, 2015. We excluded patients with chronic HCV, HDV and a history of HCC, decompensated cirrhosis or liver transplantation. Structural equation models were developed to characterize the causal pathways leading to HCC occurrence. The association between clinical characteristics (age, gender, body-mass index, liver fibrosis, alcohol consumption, smoking status, diabetes, hypertension, dyslipidemia, alpha-fetoprotein, HBV DNA levels, antiviral therapy) and incident HCC was quantified.

Results: Among the 4,489 patients included, 33 patients reported incident HCC. The median follow-up was 45.2 months. Age (β = 0.18 by decade, 95% CI 0.14-0.23), male gender (β = 0.23, 95% CI 0.18-0.29), metabolic syndrome (β = 0.28, 95% CI 0.22-0.33), alcohol consumption (β = 0.09, 95% CI 0.05-0.14) and HBV DNA (β = 0.25, 95% CI 0.17-0.34) had a significant and direct effect on the occurrence of advanced liver fibrosis. Liver fibrosis (β = 0.71, 95% CI 0.55-0.87) predicted, in turn, the occurrence of HCC.

Conclusions: Liver fibrosis mediates the effects of age, gender, alcohol, metabolic syndrome and HBV DNA on the occurrence of HCC. Elderly men with chronic hepatitis B, risky alcohol use, advanced liver fibrosis, metabolic syndrome and high HBV DNA levels should be monitored closely to detect the development of HCC.
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http://dx.doi.org/10.1016/j.clinre.2021.101713DOI Listing
April 2021

Review article: immunisation against hepatitis B virus infection and the prevention of hepatocellular carcinoma.

Aliment Pharmacol Ther 2021 Jun 28;53(11):1166-1182. Epub 2021 Apr 28.

Département d'Hépatologie, Université Paris Centre, Hôpital Cochin, APHP, INSERM U1223, Institut Pasteur, Paris, France.

Background: Chronic hepatitis B virus (HBV) infection results in a high risk of cirrhosis and its complications: cirrhosis decompensation, hepatocellular carcinoma (HCC, the fourth most common cause of cancer-related mortality worldwide), liver transplantation and death. It is now 40 years since development of the first plasmatic vaccine which has been proven to prevent (liver) cancer.

Aims: To update firstly the molecular and epidemiological aspects of HBV-related HCC and its natural history together with the benefits associated with viral suppression and secondly the safety, immunogenicity and efficacy of HBV vaccination.

Methods: Analysis of recent published data regarding HBV replication, anti-viral treatments and vaccination.

Results: The nuclear HBV replication cycle in the hepatocyte combines two limiting steps to achievement of HBV cure during chronic infection: the formation of a minichromosome, the supercoiled cccDNA, and host-genome integration of HBV DNA which triggers direct viral hepatocarcinogenesis. Even if specific anti-viral treatments significantly reduce viral replication, they decrease but do not cancel the risk of liver-related events in contrast with the prevention of HBV through HBV vaccination.

Conclusions: To achieve the 2030 viral hepatitis elimination plan, the HBV vaccine is a priority tool for achieving the sustainable development goals of the World Health Organization.
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http://dx.doi.org/10.1111/apt.16356DOI Listing
June 2021

Letter: tenofovir may be superior to entecavir for treatment-naïve chronic hepatitis B patients-authors' reply.

Aliment Pharmacol Ther 2021 05;53(9):1050

INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, IPLESP, Sorbonne Université, Paris, France.

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http://dx.doi.org/10.1111/apt.16340DOI Listing
May 2021

Hepatocellular carcinoma recurrence after direct-acting antiviral therapy: an individual patient data meta-analysis.

Gut 2021 Mar 19. Epub 2021 Mar 19.

Liver and Transplant Unit, Policlinico Tor Vergata, Rome, Italy.

Objective: The benefit of direct-acting antivirals (DAAs) against HCV following successful treatment of hepatocellular carcinoma (HCC) remains controversial. This meta-analysis of individual patient data assessed HCC recurrence risk following DAA administration.

Design: We pooled the data of 977 consecutive patients from 21 studies of HCV-related cirrhosis and HCC, who achieved complete radiological response after surgical/locoregional treatments and received DAAs (DAA group). Recurrence or death risk was expressed as HCC recurrence or death per 100 person-years (100PY). Propensity score-matched patients from the ITA.LI.CA. cohort (n=328) served as DAA-unexposed controls (no-DAA group). Risk factors for HCC recurrence were identified using random-effects Poisson.

Results: Recurrence rate and death risk per 100PY in DAA-treated patients were 20 (95% CI 13.9 to 29.8, I=74.6%) and 5.7 (2.5 to 15.3, I=54.3), respectively. Predictive factors for recurrence were alpha-fetoprotein logarithm (relative risk (RR)=1.11, 95% CI 1.03 to 1.19; p=0.01, per 1 log of ng/mL), HCC recurrence history pre-DAA initiation (RR=1.11, 95% CI 1.07 to 1.16; p<0.001), performance status (2 vs 0, RR=4.35, 95% CI 1.54 to 11.11; 2 vs 1, RR=3.7, 95% CI 1.3 to 11.11; p=0.01) and tumour burden pre-HCC treatment (multifocal vs solitary nodule, RR=1.75, 95% CI 1.25 to 2.43; p<0.001). No significant difference was observed in RR between the DAA-exposed and DAA-unexposed groups in propensity score-matched patients (RR=0.64, 95% CI 0.37 to 1.1; p=0.1).

Conclusion: Effects of DAA exposure on HCC recurrence risk remain inconclusive. Active clinical and radiological follow-up of patients with HCC after HCV eradication with DAA is justified.
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http://dx.doi.org/10.1136/gutjnl-2020-323663DOI Listing
March 2021

LI-RADS v2018 major criteria: Do hepatocellular carcinomas in non-alcoholic steatohepatitis differ from those in virus-induced chronic liver disease on MRI?

Eur J Radiol 2021 May 11;138:109651. Epub 2021 Mar 11.

Department of Radiology, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, 75014, Paris, France; Université de Paris, 75006, Paris, France.

Purpose: LI-RADS v2018 diagnostic system is used to diagnose hepatocellular carcinoma (HCC) in at risk patients. However, its applicability to HCC in non-alcoholic steatohepatitis (NASH) has not been specifically studied. The purpose of this study was to assess the applicability of LI-RADS v2018 diagnostic system for HCC in patients with NASH.

Materials And Methods: The MRI examinations of 41 patients with HCC and NASH (NASH group) were reviewed and compared to those obtained in 41 patients with HCC and virus-induced chronic liver disease (Virus group). MRI examinations of the two groups were compared for imaging presentation, LI-RADS major criteria and LI-RADS categorization. Qualitative variables were compared using Fisher exact test and quantitative variables using Mann-Whitney U test Interreader agreement was assessed using kappa statistic.

Results: No significant differences in qualitative and quantitative variables were observed between the two groups. Most common findings in the two groups were hyperenhancement during the arterial phase and visibility on T2-weighted images (93 % vs. 98 %, P = 0.616 and 85 % vs. 88 %, P = 1.000 for NASH group and Virus group, respectively). No differences in prevalence between the two groups were found for any major LI-RADS v2018 criterion. Interreader agreement for LI-RADS categorization was strong for the NASH group (kappa = 0.802) and moderate for the virus group (kappa = 0.720). No differences were found between the two groups for LI-RADS categories (P =  0.303).

Conclusions: The LI-RADS v2018 diagnostic algorithm can be applied in patients with NASH.
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http://dx.doi.org/10.1016/j.ejrad.2021.109651DOI Listing
May 2021

[The therapeutic revolution of hepatitis C virus infection honored by a Nobel prize].

Authors:
Stanislas Pol

Rev Prat 2020 Nov;70(9):935-941

Université de Paris ; Inserm U-1223, Institut Pasteur, Paris, France Département d'hépatologie, AP-HP, hôpital Cochin, Paris, France.

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November 2020

Adult human liver slice cultures: Modelling of liver fibrosis and evaluation of new anti-fibrotic drugs.

World J Hepatol 2021 Feb;13(2):187-217

Institut Pasteur, Immunobiologie des Cellules Dendritiques, INSERM U1223, Paris 75015, France.

Background: Liver fibrosis can result in end-stage liver failure and death.

Aim: To examine human liver fibrogenesis and anti-fibrotic therapies, we evaluated the three dimensional liver slice (LS) model.

Methods: Fibrotic liver samples (F0 to F4 fibrosis stage according to the METAVIR score) were collected from patients after liver resection. Human liver slices (HLS) were cultivated for up to 21 days. Hepatitis C virus (HCV) infection, alcohol (ethanol stimulation) and steatosis (palmitate stimulation) were examined in fibrotic (F2 to F4) liver slices infected (or not) with HCV. F0-F1 HLS were used as controls. At day 0, either ursodeoxycholic acid (choleretic and hepatoprotective properties) and/or α-tocopherol (antioxidant properties) were added to standard of care on HLS and fibrotic liver slices, infected (or not) with HCV. Expression of the biomarkers of fibrosis and the triglyceride production were checked by quantitative reverse transcription polymerase chain reaction and/or enzyme-linked immunosorbent assay.

Results: The cultures were viable for 21 days allowing to study fibrosis inducers and to estimate the effect of anti-fibrotic drugs. Expression of the biomarkers of fibrosis and the progression to steatosis (estimated by triglycerides production) was increased with the addition of HCV and /or ethanol or palmitate. From day 15 of the follow-up studies, a significant decrease of both transforming growth factor β-1 and Procol1A1 expression and triglycerides production was observed when a combined anti-fibrotic treatment was applied on HCV infected F2-F4 LS cultures.

Conclusion: These results show that the human three dimensional model effectively reflects the processes in damaged human liver (viral, alcoholic, nonalcoholic steatohepatitis liver diseases) and provides the proof of concept that the LS examined model permits a rapid evaluation of new anti-fibrotic therapies when used alone or in combination.
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http://dx.doi.org/10.4254/wjh.v13.i2.187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934011PMC
February 2021

HCV Eradication in Primary or Secondary Prevention Optimizes Hepatocellular Carcinoma Curative Management.

Cancer Prev Res (Phila) 2021 May 19;14(5):581-592. Epub 2021 Feb 19.

Service d'Hépatologie et Université de Lyon, Hospices Civils de Lyon, Lyon, France.

To assess the impact of HCV eradication on the outcomes of cirrhotic patients treated curatively for incidental hepatocellular carcinoma (HCC) detected during surveillance program. Data were collected on 1,323 French patients with compensated biopsy-proven HCV cirrhosis recruited in 35 centers (ANRS CO12 CirVir cohort). Sustained virologic responses (SVR) and the occurrence of HCC were recorded prospectively. During a median follow-up of 68.3 months, 218 patients developed HCC, 126 of whom underwent a curative procedure as first-line therapy (ablation = 95, resection = 31). The HCC BCLC stage was 0/A in 97.5% of patients; 74 (58.7%) never achieved SVR. During a median follow-up of 26.0 months after HCC treatment, 59 (46.8%) experienced HCC recurrence. SVR was not associated with a recurrence, whether considering final SVR status [HR = 0.77; 95% confidence interval (95% CI), 0.43-1.39; = 0.39] or its time to achievement (prior to/after HCC occurrence; global = 0.28). During the same timeframe, 46 patients with HCC (36.5%) died (liver failure: 41.9%, HCC progression: 37.2%, extrahepatic causes: 20.9%). Under multivariate analysis, SVR was associated with improved survival [HR = 0.21; 95% CI, 0.08-0.52; = 0.001]. Survival benefit was explained by a lower incidence of liver decompensation and higher rates of sequential HCC re-treatment. Direct antiviral intake was not associated with a higher risk of HCC recurrence, but with improved survival (HR = 0.23; 95% CI, 0.06-0.83; = 0.024). HCV eradication in primary or secondary prevention optimizes HCC management through preservation of liver function and improves survival, whatever the regimen. PREVENTION RELEVANCE: Liver failure is a competing risk of death in patients with HCC eligible for curative procedures. HCV eradication does not decrease risk of HCC recurrence in the first two years, but enables sequential curative HCC treatments through preservation of liver function. Direct-acting antiviral agent intake is not associated with HCC recurrence and improves survival.
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http://dx.doi.org/10.1158/1940-6207.CAPR-20-0465DOI Listing
May 2021

Effectiveness of direct-acting antivirals for chronic hepatitis C treatment in migrant and non-migrant populations in France.

Liver Int 2021 Feb 16. Epub 2021 Feb 16.

Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, Marseille, France.

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.
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http://dx.doi.org/10.1111/liv.14823DOI Listing
February 2021

Editorial: similar risk of hepatocellular carcinoma in chronic hepatitis B patients treated with tenofovir or entecavir-new clues from Europe. Authors' reply.

Aliment Pharmacol Ther 2021 03;53(5):659

Sorbonne Université, Institut National de la santé et de la Recherche Médicale, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.

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http://dx.doi.org/10.1111/apt.16251DOI Listing
March 2021

Two-dimensional shear wave elastography predicts survival in advanced chronic liver disease.

Gut 2021 Jan 21. Epub 2021 Jan 21.

Department of Radiology, Beaujon University Hospital, Clichy, France.

Objective: Liver stiffness measurement (LSM) is a tool used to screen for significant fibrosis and portal hypertension. The aim of this retrospective multicentre study was to develop an easy tool using LSM for clinical outcomes in advanced chronic liver disease (ACLD) patients.

Design: This international multicentre cohort study included a derivation ACLD patient cohort with valid two-dimensional shear wave elastography (2D-SWE) results. Clinical and laboratory parameters at baseline and during follow-up were recorded. LSM by transient elastography (TE) was also recorded if available. The primary outcome was overall mortality. The secondary outcome was the development of first/further decompensation.

Results: After screening 2148 patients (16 centres), 1827 patients (55 years, 62.4% men) were included in the 2D-SWE cohort, with median liver SWE (L-SWE) 11.8 kPa and a model for end stage liver disease (MELD) score of 8. Combination of MELD score and L-SWE predict independently of mortality (AUC 0.8). L-SWE cut-off at ≥20 kPa combined with MELD ≥10 could stratify the risk of mortality and first/further decompensation in ACLD patients. The 2-year mortality and decompensation rates were 36.9% and 61.8%, respectively, in the 305 (18.3%) high-risk patients (with L-SWE ≥20 kPa and MELD ≥10), while in the 944 (56.6%) low-risk patients, these were 1.1% and 3.5%, respectively. Importantly, this M10LS20 algorithm was validated by TE-based LSM and in an additional cohort of 119 patients with valid point shear SWE-LSM.

Conclusion: The M10LS20 algorithm allows risk stratification of patients with ACLD. Patients with L-SWE ≥20 kPa and MELD ≥10 should be followed closely and receive intensified care, while patients with low risk may be managed at longer intervals.
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http://dx.doi.org/10.1136/gutjnl-2020-323419DOI Listing
January 2021

Similar 5-year HCC occurrence in Tenofovir- and Entecavir-treated HBV chronic infection in the French AFEF/ANRS CO22 Hepather cohort.

Authors:
Stanislas Pol

Aliment Pharmacol Ther 2021 03 19;53(5):616-629. Epub 2021 Jan 19.

Assistance Publique - Hôpitaux de Paris, Hôpital Cochin, Unité d'Hépatologie, Paris, France.

Background: Chronic hepatitis B virus (HBV) infection results in a high risk of cirrhosis and its complications, cirrhosis decompensation (DC), hepatocellular carcinoma (HCC), liver transplantation (LT), death or any of these outcomes (composite endpoint [CE]). Nucleos(t)ide analogues (NUCs) such as tenofovir or entecavir are associated with a reduction in these complications.

Aim: To compare the impact of tenofovir and entecavir on these outcomes in patients treated for HBV infection and included in the prospective Hepather cohort.

Methods: All patients with HBV infection who had received tenofovir or entecavir for more than 6 months at or after entry in the ANRS CO22 cohort were selected. Patients with HDV and HCV co-infection or prior liver event were excluded. Incidence rates of events were compared using inverse probability of treatment weighting (IPW).

Results: The cohort included 1800 patients (986 tenofovir and 814 entecavir). Median follow-up was 4.2 years. The incidences of HCC, DC, LT, ACD, LRD and CE were not different between tenofovir- (1.8 (0.9; 3.2), 0.6 (0.2; 1.6), 0.2 (0.0; 0.8), 1.7 (0.8; 3.0), 0.8 (0.2, 1.8) and 4.1 (3.0; 5.4) per 1000 person-years) and entecavir-treated patients (1.6 (0.7; 3.0), 0.7 (0.2; 1.8), 0.2 (0.0; 1.0), 3.0 (1.7, 4.8), 0.5 (0.1; 1.5) and 5.0 (3.3; 7.2)) per 1000 person-years, respectively.

Conclusion: The risk of liver-related events or death was not different between tenofovir- and entecavir-treated patients in this large prospective cohort of predominantly non-cirrhotic French patients.

Trial Registration Number: NCT019553458.
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http://dx.doi.org/10.1111/apt.16197DOI Listing
March 2021

Treatment of hepatitis C virus infection.

Clin Res Hepatol Gastroenterol 2020 Nov 30:101578. Epub 2020 Nov 30.

Département d'Hépatologie, APHP, Hôpital Cochin, Paris, France; Université de Paris, Inserm U-1223 et Immunité des Cellules Dendritiques, Institut Pasteur, Paris, France. Electronic address:

Hepatitis C virus infection affects 71 million people worldwide. It is at the origin of a multi-organ disease associating hepatic manifestations, cryoglobulinemic vasculitis and general manifestations linked to chronic inflammation (diabetes, cardio-, reno- or cerebrovascular manifestations, extra-hepatic cancers including non-Hodgkin's lymphoma). The significant morbidity and mortality linked to the hepatitis C virus therefore justify its screening and access to treatments which have increased considerably over the past two decades. Understanding the replicative cycle of the hepatitis C virus has enabled the development of direct HCV-specific antivirals targeting viral proteins (NS3/4A protease, NS5B polymerase and the multifunctional NS5A replication complex). The combination of two to three specific inhibitors often co-formulated in a capsule, without pegylated interferon and most often without ribavirin, allows high antiviral efficacy (more than 97% cure) for a treatment duration of 8-12 weeks with satisfactory tolerance. HCV infection is the only chronic viral infection that can be cured and the hepatic or extrahepatic manifestations are mainly reversible. This underlines the importance of strengthening screening and access to care policies in order to achieve the elimination of viral infection C in the short term, in 2030, as expected from the program of the World Health Organization. If this elimination is possible in some countries (Iceland, France, Germany …), it seems compromised in others where prevention (USA), screening and/or access to care are still insufficient (Sub-Saharan Africa, Russia…).
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http://dx.doi.org/10.1016/j.clinre.2020.11.008DOI Listing
November 2020

Acceptability of on-site rapid HIV/HBV/HCV testing and HBV vaccination among three at-risk populations in distinct community-healthcare outreach centres: the ANRS-SHS 154 CUBE study.

BMC Infect Dis 2020 Nov 16;20(1):851. Epub 2020 Nov 16.

Inserm, IPLESP, ERES, Institut Pierre-Louis d'épidémiologie et de santé publique, Sorbonne Université, 75012, Paris, France.

Background: HIV, HBV and HCV infections continue to represent major health concerns, especially among key at-risk populations such as men who have sex with men (MSM), people who inject drugs (PWIDs), transgender women (TGW) and sex workers (SW). The objective of the ANRS-CUBE study was to evaluate the acceptability of a healthcare, community-based strategy offering a triple rapid HIV-HBV-HCV testing, and HBV vaccination, targeted at three priority groups (MSM, PWIDs and TGW/SWs), in three community centers, in the Paris area.

Methods: This longitudinal multicentric non-randomized study included all adult volunteers attending one of the three specialized community centers in Paris, between July 2014 and December 2015. HIV, HBV and HCV status and acceptability of HBV vaccination were evaluated.

Results: A total of 3662, MSM, 80 PWIDs and 72 TGW/SW were recruited in the three centers respectively. Acceptability of rapid tests was 98.5% in MSM and 14.9% in TGW/SWs, but could not be estimated in PWIDs since the number of users attending and the number of proposals were not recorded. User acceptability of HBV vaccination was weak, only 17.9% of the eligible MSM (neither vaccinated, nor infected) agreed to receive the first dose, 12.2% two doses, 5.9% had a complete vaccination. User acceptability of HBV vaccination was greater in PWIDs and TGW/SWs, but decreased for the last doses (66.7 and 53.3% respectively received a first dose, 24.4 and 26.7% a second dose and 6.7 and 0% a third dose). Fifty-three participants (49 MSM and 4 PWIDs) were discovered HIV positive, more than half with a recent infection. All but two HIV positive participants were linked to appropriate care in less than one month.

Conclusions: Rapid HIV-HCV-HBV screening showed a very high level of acceptability among MSM. Efforts need to be made to improve immediate acceptability for HBV vaccination, especially among MSM, and follow-up doses compliance. Our results show the important role of community centers in reaching targets, often fragile, populations, while also suggesting the need to reinforce on-site human support in terms of testing and vaccination, especially when addressing PWIDs.
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http://dx.doi.org/10.1186/s12879-020-05601-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670674PMC
November 2020

Impact of COVID-19 on the management of hepatocellular carcinoma in a high-prevalence area.

JHEP Rep 2021 Feb 22;3(1):100199. Epub 2020 Dec 22.

Service d'Hépatologie, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bondy, France.

Background & Aims: Patients affected by hepatocellular carcinoma (HCC) represent a vulnerable population during the COVID-19 pandemic and may suffer from altered allocation of healthcare resources. The aim of this study was to determine the impact of the COVID-19 pandemic on the management of patients with HCC within 6 referral centres in the metropolitan area of Paris, France.

Methods: We performed a multicentre, retrospective, cross-sectional study on the management of patients with HCC during the first 6 weeks of the COVID-19 pandemic (exposed group), compared with the same period in 2019 (unexposed group). We included all patients discussed in multidisciplinary tumour board (MTB) meetings and/or patients undergoing a radiological or surgical programmed procedure during the study period, with curative or palliative intent. Endpoints were the number of patients with a modification in the treatment strategy, or a delay in decision-to-treat.

Results: After screening, n = 670 patients were included (n = 293 exposed to COVID, n = 377 unexposed to COVID). Fewer patients with HCC presented to the MTB in 2020 ( = 0.034) and fewer had a first diagnosis of HCC (n = 104 exposed to COVID, n = 143 unexposed to COVID,  = 0.083). Treatment strategy was modified in 13.1% of patients, with no differences between the 2 periods. Nevertheless, 21.5% 9.5% of patients experienced a treatment delay longer than 1 month in 2020 compared with 2019 ( <0.001). In 2020, 7.1% (21/293) of patients had a diagnosis of an active COVID-19 infection: 11 (52.4%) patients were hospitalised and 4 (19.1%) patients died.

Conclusions: In a metropolitan area highly impacted by the COVID-19 pandemic, we observed fewer patients with HCC, and similar rates of treatment modification, but with a significantly longer treatment delay in 2020  2019.

Lay Summary: During the coronavirus disease 2019 (COVID-19) pandemic era, fewer patients with hepatocellular carcinoma (HCC) presented to the multidisciplinary tumour board, especially with a first diagnosis of HCC. Patients with HCC had a treatment delay that was longer in the COVID-19 period than in 2019.
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http://dx.doi.org/10.1016/j.jhepr.2020.100199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604130PMC
February 2021

Cannabis use is associated with a lower risk of diabetes in chronic hepatitis C-infected patients (ANRS CO22 Hepather cohort).

J Viral Hepat 2020 12 8;27(12):1473-1483. Epub 2020 Sep 8.

Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques & Sociales de la Santé & Traitement de l'Information Médicale, Marseille, France.

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 < .001) cannabis use were both associated with a reduced odds of diabetes. Conversely, male gender, tobacco use, elevated BMI, poverty, being a migrant and advanced fibrosis were associated with increased odds of diabetes. The association between cannabis use and diabetes was maintained in the stratified analysis. In this large cross-sectional study of chronic HCV-infected patients, cannabis use was associated with a lower risk of diabetes independently of clinical and socio-behavioural factors. Further studies are needed to elucidate a potential causal link and shed light on cannabis compounds and mechanisms involved in this relationship.
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http://dx.doi.org/10.1111/jvh.13380DOI Listing
December 2020

Increased mortality in HIV/HCV-coinfected compared to HCV-monoinfected patients in the DAA era due to non-liver-related death.

J Hepatol 2021 Jan 14;74(1):37-47. Epub 2020 Aug 14.

ISPED, INSERM, Bordeaux Population Health Research Center, Team MORPH3EUS, UMR 1219, CIC-EC 1401, University of Bordeaux, Bordeaux, France; CHU de Bordeaux, Pôle de Santé Publique, Bordeaux, France. Electronic address:

Background & Aims: Direct-acting antivirals (DAA) lead to high sustained virological response (SVR) rates and decrease the risk of disease progression. We compared SVR rates and all-cause, liver- and non-liver-related deaths, liver-related events, and non-liver-related cancers in HIV/HCV-coinfected and HCV-monoinfected participants from 2 French cohort studies after initiation of DAA treatment.

Methods: Up to 4 HCV-monoinfected participants from the ANRS CO22 HEPATHER cohort were matched by age and sex to each HIV/HCV-coinfected patient from the ANRS CO13 HEPAVIH cohort; both are nationwide, prospective, multicentre, and observational. Participants were initiated on DAAs between March 2014 and December 2017. Cox proportional hazards models adjusted by age, sex, duration since HCV diagnosis, HCV transmission routes, HCV genotypes, cirrhosis, tobacco, alcohol consumption, and SVR (time dependent) were used.

Results: A total of 592 HIV/HCV-coinfected and 2,049 HCV-monoinfected participants were included; median age was 53.3 years (inter-quartile range: 49.6-56.9) and 52.9 years (49.6; 56.7), 1,498 (73.1%) and 436 (73.6%) were men, and 159 (28.8%) and 793 (41.2%) had cirrhosis, respectively. SVR was observed in 92.9% and 94.6%, respectively. HIV coinfection was associated with higher risk of all-cause death (hazard ratio [HR] 1.93; 95% CI 1.01-3.69), non-liver-related death (HR 2.84; 95% CI 1.27-6.36), and non-liver-related cancer (HR 3.26; 95% CI 1.50-7.08), but not with liver-related-death (HR 1.04; 95% CI 0.34-3.15) or liver-related events (HR 0.66; 95% CI 0.31-1.44).

Conclusions: After DAA treatment, HIV-coinfected individuals had similar SVR rates and risk of liver-related deaths and events compared with HCV-monoinfected individuals, but had a higher risk of all-cause and non-liver-related deaths and non-liver-related cancers.

Lay Summary: We compared the risk of several clinical events in participants infected by human immunodeficiency virus and hepatitis C virus with those infected with hepatitis C virus alone, matched on age and sex, after treatment with contemporary direct-acting antivirals. We found a higher risk of all-cause deaths, non-liver-related deaths, and non-liver-related cancers in participants coinfected with the human immunodeficiency virus and hepatitis C virus, and no differences for the risk of liver-related deaths or events.
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http://dx.doi.org/10.1016/j.jhep.2020.08.008DOI Listing
January 2021

Personalized surveillance for hepatocellular carcinoma in cirrhosis - using machine learning adapted to HCV status.

J Hepatol 2020 12 29;73(6):1434-1445. Epub 2020 Jun 29.

AP-HP, Groupe Hospitalier de La Pitié-Salpêtrière, Service d'Hépatologie, Paris.

Background & Aims: Refining hepatocellular carcinoma (HCC) surveillance programs requires improved individual risk prediction. Thus, we aimed to develop algorithms based on machine learning approaches to predict the risk of HCC more accurately in patients with HCV-related cirrhosis, according to their virological status.

Methods: Patients with compensated biopsy-proven HCV-related cirrhosis from the French ANRS CO12 CirVir cohort were included in a semi-annual HCC surveillance program. Three prognostic models for HCC occurrence were built, using (i) Fine-Gray regression as a benchmark, (ii) single decision tree (DT), and (iii) random survival forest for competing risks survival (RSF). Model performance was evaluated from C-indexes validated externally in the ANRS CO22 Hepather cohort (n = 668 enrolled between 08/2012-01/2014).

Results: Out of 836 patients analyzed, 156 (19%) developed HCC and 434 (52%) achieved sustained virological response (SVR) (median follow-up 63 months). Fine-Gray regression models identified 6 independent predictors of HCC occurrence in patients before SVR (past excessive alcohol intake, genotype 1, elevated AFP and GGT, low platelet count and albuminemia) and 3 in patients after SVR (elevated AST, low platelet count and shorter prothrombin time). DT analysis confirmed these associations but revealed more complex interactions, yielding 8 patient groups with varying cancer risks and predictors depending on SVR achievement. On RSF analysis, the most important predictors of HCC varied by SVR status (non-SVR: platelet count, GGT, AFP and albuminemia; SVR: prothrombin time, ALT, age and platelet count). Externally validated C-indexes before/after SVR were 0.64/0.64 [Fine-Gray], 0.60/62 [DT] and 0.71/0.70 [RSF].

Conclusions: Risk factors for hepatocarcinogenesis differ according to SVR status. Machine learning algorithms can refine HCC risk assessment by revealing complex interactions between cancer predictors. Such approaches could be used to develop more cost-effective tailored surveillance programs.

Lay Summary: Patients with HCV-related cirrhosis must be included in liver cancer surveillance programs, which rely on ultrasound examination every 6 months. Hepatocellular carcinoma (HCC) screening is hampered by sensitivity issues, leading to late cancer diagnoses in a substantial number of patients. Refining surveillance periodicity and modality using more sophisticated imaging techniques such as MRI may only be cost-effective in patients with the highest HCC incidence. Herein, we demonstrate how machine learning algorithms (i.e. data-driven mathematical models to make predictions or decisions), can refine individualized risk prediction.
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http://dx.doi.org/10.1016/j.jhep.2020.05.052DOI Listing
December 2020

Absence of impact of direct acting antivirals for hepatitis C virus on recurrent hepatocellular carcinoma tumor growth in the AFEF/ANRS CO22 Hepather cohort.

Clin Res Hepatol Gastroenterol 2021 Jan 25;45(1):101459. Epub 2020 Jun 25.

Hepatology Unit, Hôpital Cochin, AP-HP, 27, rue du Fg Saint-Jacques, 75014 Paris, France.

Background: Although it has now been excluded that direct-acting antivirals (DAA) are associated with a significant risk of hepatocellular carcinoma (HCC) in HCV-infected patients, a possible effect of DAA on tumor growth is still a subject of debate. We performed a blind comparison of the kinetics of HCC recurrence in patients after HCV treatment with or without DAA to evaluate the potential aggressiveness of HCC after DAA treatment.

Basic Procedures: Thirty-nine HCV-infected patients from the AFEF/ANRS CO22 Hepather cohort who experienced HCC recurrence after so-called curative treatment were evaluated. Contrast-enhanced CT and/or MR images were read blindly 6 months before HCC recurrence and during the follow-up period. Seventeen patients who received DAA (DAA+) before HCC recurrence were compared to the 22 who did not receive (DAA-), according to the LiRads and mRECIST criteria.

Main Findings: There were 28 men and 11 women, median age 62 years old, 37 (95%) with cirrhosis. DAA+ patients had a lower median MELD score (8±2 vs. 10±4, P=0.0286) than DAA- patients. The median time to HCC recurrence (time from the date of curative treatment to the diagnosis of recurrence) was not different (20 vs. 18 months) (P=0.73) between the two groups. There was no difference between the 2 groups in the overall survival and/or transplantation-free survival (P=0.71) and for the mRECIST time to progression (P=0.25).

Conclusion: This blinded analysis of HCC recurrence after HCC treatment does not support any negative impact of DAA therapy on the severity or progression of recurrent HCC.
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http://dx.doi.org/10.1016/j.clinre.2020.04.022DOI Listing
January 2021

Reply to "Precision-cut human liver slice cultures as an immunological platform".

J Immunol Methods 2020 Jun 25:112814. Epub 2020 Jun 25.

INSERM U-1223, Pasteur Institute, Paris, France; Paris Descartes University, France; Assistance Publique - Hôpitaux de Paris, Cochin Hospital, Liver Department, Paris, France.

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http://dx.doi.org/10.1016/j.jim.2020.112814DOI Listing
June 2020

Potent human broadly neutralizing antibodies to hepatitis B virus from natural controllers.

J Exp Med 2020 10;217(10)

Laboratory of Humoral Immunology, Department of Immunology, Institut Pasteur, Paris, France.

Rare individuals can naturally clear chronic hepatitis B virus (HBV) infection and acquire protection from reinfection as conferred by vaccination. To examine the protective humoral response against HBV, we cloned and characterized human antibodies specific to the viral surface glycoproteins (HBsAg) from memory B cells of HBV vaccinees and controllers. We found that human HBV antibodies are encoded by a diverse set of immunoglobulin genes and recognize various conformational HBsAg epitopes. Strikingly, HBsAg-specific memory B cells from natural controllers mainly produced neutralizing antibodies able to cross-react with several viral genotypes. Furthermore, monotherapy with the potent broadly neutralizing antibody Bc1.187 suppressed viremia in vivo in HBV mouse models and led to post-therapy control of the infection in a fraction of animals. Thus, human neutralizing HBsAg antibodies appear to play a key role in the spontaneous control of HBV and represent promising immunotherapeutic tools for achieving HBV functional cure in chronically infected humans.
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http://dx.doi.org/10.1084/jem.20200840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537403PMC
October 2020

Sofosbuvir-Daclatasvir is suboptimal in patients with genotype 2 chronic hepatitis C infection: real-life experience from the HEPATHER ANRS CO22 cohort.

J Viral Hepat 2020 10 21;27(10):964-973. Epub 2020 May 21.

Hepatology Unit, APHP Cochin, Paris, France.

Sofosbuvir plus daclatasvir with or without ribavirin has demonstrated a high efficacy and an acceptable safety profile in clinical trials of patients infected with genotype 2 hepatitis Cvirus (HCV); however, there are currently no real-world data available for this regimen. To evaluate the real-life safety and efficacy of sofosbuvir/daclatasvir with or without ribavirin in genotype 2 HCV patients in the French cohort ANRS CO22 HEPATHER(NCT01953458). In this ongoing, national, multicentre, prospective, observational study, we observed patients with HCV genotype 2 infection who initiated treatment with sofosbuvir (400 mg/d) plus daclatasvir with or without ribavirin (1-1.2 g/d). Patients were divided into two treatment groups: sofosbuvir/daclatasvir with or without ribavirin (12 weeks/24 weeks). The primary end point was a sustained virological response at week 12 following the end of therapy. Overall, 88% and 91% of patients achieved a sustained virological response following 12 and 24 weeks of treatment with sofosbuvir/daclatasvir with or without ribavirin, respectively. The most common adverse events were asthenia (29%), headache (15%) and fatigue (20%), and ribavirin addition was associated with a higher rate of adverse events and treatment discontinuation. Sofosbuvir/daclatasvir with or without ribavirin was associated with lower rates of sustained virological response in the real-life setting compared with the clinical setting and demonstrated suboptimal efficacy for the treatment of patients with genotype 2 chronic HCV.
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http://dx.doi.org/10.1111/jvh.13321DOI Listing
October 2020

Phase 3, Multicenter Open-Label study to investigate the efficacy of elbasvir and grazoprevir fixed-dose combination for 8 weeks in treatment-naïve, HCV GT1b-infected patients, with non-severe fibrosis.

Liver Int 2020 08 1;40(8):1853-1859. Epub 2020 Jun 1.

Service de médecine digestive et hépato-biliaire CHU Estaing, Clermont-Ferrand, France.

Background: Genotype 1b is the most common HCV genotype worldwide, accounting for the largest proportion of infections in Europe, Russia, Latin America and Asia. Reducing treatment duration can improve adherence, reduce drug exposure and cost. Accordingly, we evaluated the efficacy of 8 weeks fixed-dose combination of grazoprevir-elbasvir in treatment-naïve patients, with non-severe fibrosis.

Methods: HCV mono-infected and treatment naïve patients with non-severe fibrosis (Fibroscan <9.5 kPa and Fibrotest  < 0.59) were enrolled in a study which included 117 patients. Genotyping by sequencing identified five patients with non-1b genotype (two GT1a, one GT1h, one GT1e and one GT1l). Thus, we included in the final analysis 112 GT1b patients. The primary end point was the proportion of patients with HCVRNA below the lower limit of quantification 12 weeks after treatment (SVR12).

Findings: Mean age was 54 ± 13 years, 31% were men and viral load was higher than 800.000 IU/mL in 70 of 112 patients (63%). Using Fibroscan , 100 had F0-1 fibrosis score. FIB-4 lower than 1.45 and APRI less than 1 was found in 74/112 (66%) and 107/112 (95%) patients respectively. Relapse occurred in three patients by week 12. These three patients had a viral load higher than 6 million IU/mL and NS5A Y93H RAS (resistance-associated substitution). Then, modified intention-to-treat SVR12 for patients with genotype 1b was 109/112 (97%). By week 24; five relapses were observed and all had the Y93H RAS at relapse. SVR12 was achieved in 100% of patients with a baseline viral load below 6 million and decreased to 98% (98/100) by follow-up week 24.

Interpretation: Naïve patients with genotype 1b and non-severe fibrosis can achieve an SVR12 of 97% and an SVR24 of 95%. Then, these patients can be treated with grazoprevir-elbasvir for 8 weeks.
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http://dx.doi.org/10.1111/liv.14502DOI Listing
August 2020

Evolution of Hepatitis C Virus Treatment During the Era of Sofosbuvir-Based Therapies: A Real-World Experience in France.

Dig Dis Sci 2021 Mar 18;66(3):881-898. Epub 2020 Apr 18.

Département D'Hépatologie, Inserm U1223, Hôpital Cochin AP-HP, 27, rue du Faubourg Saint Jacques, 75014, Paris, France.

Background: Treatment of hepatitis C virus (HCV) has been dramatically improved with the introduction of direct-acting antiviral agents (DAAs). Universal access to pangenotypic DAAs was provided in France from 2017, expanding the type of patients treated. Real-world studies are important to confirm effectiveness and safety in clinical practice, particularly in vulnerable populations.

Aims: To assess real-world effectiveness and safety of sofosbuvir-based therapy in adults with chronic HCV infection before and after universal access to DAAs in France.

Methods: This multicenter, non-interventional, prospective study assessed the effectiveness, safety, patient-reported outcomes and adherence with sofosbuvir-based regimens from October 2015 to July 2016 (Period 1: sofosbuvir-based therapy excluding sofosbuvir/velpatasvir) and from October 2017 to July 2018 (Period 2: pangenotypic sofosbuvir/velpatasvir-based therapy).

Results: Baseline data were documented for 1029 patients. Overall, 797 (77%) had sustained virologic response data available ≥ 9 weeks after treatment completion. Per protocol response was high (97%) irrespective of age, alcohol consumption, recreational drug use, or HIV/HCV coinfection. Adverse events occurred in approximately 25% of patients with the majority experiencing Grade 1 or 2 events. Sofosbuvir-based regimens improved health-related quality of life from baseline to end of treatment in patients with data at all timepoints. Overall, 99% of patients reported total or almost total adherence to therapy.

Conclusions: Sofosbuvir-based therapy, including pangenotypic sofosbuvir/velpatasvir, is effective for the treatment of HCV in real-world clinical practice. This is an important step towards HCV elimination.
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http://dx.doi.org/10.1007/s10620-020-06234-1DOI Listing
March 2021

Micro-elimination of hepatitis C virus.

Liver Int 2020 02;40 Suppl 1:67-71

Département d'Hépatologie, Université Paris Centre, Hôpital Cochin, APHP, INSERM U1223, Institut Pasteur, Paris, France.

Background & Aims: HCV affects about 71 million people worldwide with 1.75 million new infections a year, mainly associated with healthcare, blood transfusion before screening of donors and drug use. Hepatitis C is a systemic disease with hepatic and extrahepatic manifestations resulting in increased morbidity and mortality in HCV-infected patients compared to cured or uninfected individuals.

Results: The goal of eliminating hepatitis C by 2030 is based on the following three main actions: strengthening and increasing outreach screening; increasing access to treatment; and improving prevention. Although the tools and the targets of HCV elimination have now been well established, micro-elimination, a cure in high-risk populations, is possible, but has not been achieved. These populations are mainly migrants, prisoners, drug users, HIV co-infected patients and psychiatric patients. New tools must be developed to achieve micro-elimination, in particular, rapid diagnostic orientation tests for better screening, delocalization of healthcare services to improve access to care, and training physicians to raise awareness of the disease, increase understanding of its pathogenesis and provide information on the availability of safe and effective treatment to cure chronic infection and reverse hepatic and extrahepatic manifestations.

Conclusion: Thus, while the goal of complete elimination of hepatitis C virus was feasible in Western countries, it was more difficult in high-prevalence countries where improvement in the detection of chronic infection (with rapid serological and virological diagnostic tests), outsourcing of diagnostic and therapeutic care and access to direct oral antivirals are urgently needed.
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http://dx.doi.org/10.1111/liv.14363DOI Listing
February 2020

[Editorial].

Authors:
Stanislas Pol

Presse Med 2019 12;48(12):1457-1458

AP-HP, hôpital Cochin, université Paris Descartes, département d'hépatologie, Inserm U1223, UMS-20, Institut Pasteur, 27, rue du faubourg Saint-Jacques, 75679 Paris cedex 14, France. Electronic address:

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http://dx.doi.org/10.1016/j.lpm.2019.11.004DOI Listing
December 2019

[FIB-4 index to rule-out advanced liver fibrosis in NAFLD patients].

Presse Med 2019 Dec 22;48(12):1484-1488. Epub 2019 Nov 22.

AP-HP, université Paris Descartes, Sorbonne Paris Cité, groupe hospitalier Cochin Port Royal, service hépatologie, 75014 Paris, France; Institut Pasteur, U.1223, Inserm, 75015 Paris, France.

The FIB-4 index is a biomarker of advanced hepatic fibrosis in a context of fatty liver disease. The calculation of the FIB-4 index requires of age, serum ALT and AST transaminase levels and platelet count. A FIB-4 index<1.45 in a context of fatty liver disease excludes clinically significant hepatic fibrosis. Additional explorations are mandatory to excluded hepatic fibrosis for a a FIB-4 index>1.45 in a context of fatty liver disease. A complete hepatological workup is mandatory for a FIB-4 index>3.25 in a context of fatty liver disease.
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http://dx.doi.org/10.1016/j.lpm.2019.10.017DOI Listing
December 2019

Efficacy and safety of elbasvir/grazoprevir for 8 or 12 weeks for hepatitis C virus genotype 4 infection: A randomized study.

Liver Int 2020 05 22;40(5):1042-1051. Epub 2020 Mar 22.

Department of Hepatology, Hôpital de Hautepierre, Universitaires de Strasbourg, Strasbourg, France.

Background & Aims: Hepatitis C virus (HCV) genotype (GT) 4 infection is prevalent in sub-Saharan Africa and the Middle East, particularly in Egypt. This study evaluated the safety and efficacy of elbasvir/grazoprevir administered for 8 and 12 weeks in participants with HCV GT4 infection.

Methods: In this partially randomized, open-label multicentre study conducted in France (NCT03111108; Protocol MK5172-096), treatment-naive participants with GT4 infection and F0-F2 fibrosis were randomized 2:1 to elbasvir (50 mg)/grazoprevir (100 mg) for 8 or 12 weeks. Treatment-naive participants with F3-F4 fibrosis and all treatment-experienced participants (F0-F4) were assigned to elbasvir/grazoprevir for 12 weeks. The primary endpoint was sustained virologic response (SVR) 12 weeks after the end of therapy.

Results: One hundred and seventeen participants were enrolled. Among treatment-naive participants with F0-F2 fibrosis, SVR was achieved by 94% (50/53) and 96% (26/27) of those receiving elbasvir/grazoprevir for 8 or 12 weeks, respectively, and four participants relapsed. In the 12-week arm, 95% (35/37) achieved SVR and two participants relapsed. NS5A resistance-associated substitutions were present at baseline and virologic failure in five of the participants with relapse. Drug-related adverse events occurred in 42% (n = 22) and 50% (n = 32) of participants receiving 8 and 12 weeks of treatment, respectively. No participant discontinued treatment owing to an adverse event.

Conclusion: These data confirm the efficacy of elbasvir/grazoprevir administered for 12 weeks in treatment-experienced individuals with HCV GT4 infection and those with advanced fibrosis. Treatment-naive individuals with mild fibrosis can be treated effectively with an 8-week regimen.
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http://dx.doi.org/10.1111/liv.14313DOI Listing
May 2020

[Epidemiology of non-alcoholic steatohepatitis. Extent/burden of the problem and its impact on public health].

Presse Med 2019 Dec 19;48(12):1459-1467. Epub 2019 Nov 19.

Hôpital Cochin, département d'hépatologie, 27, rue du Fg-Saint-Jacques, 75014 ParisFrance; AP-HP, université Paris Descartes, 15, rue de l'École de Médecine, 75006 Paris, France; Institut Pasteur, Inserm U1223, UMS-20, 25-28, rue du Docteur-Roux, 75015 Paris France.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease, the most common cause of chronic liver function augmentation and it will be the most common indication for liver transplantation in 2020. The prevalence of NAFLD has increased over time in line with the increase of obesity and type 2 diabetes. There is a discrepancy between the studies concerning the prevalence of NAFLD because of the different diagnostic methods used (ultrasound or magnetic resonance, fibroscan, controlled attenuation parameter (CAP), histology). Because of its high prevalence the impact of NAFLD in public health is real. Therapeutic advances must be made to better understand the natural history of NAFLD and improve the management of this emerging liver disease.
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http://dx.doi.org/10.1016/j.lpm.2019.08.008DOI Listing
December 2019