Neo-Adjuvant Use of Sorafenib for Hepatocellular Carcinoma Awaiting Liver Transplantation.

Data on efficacy and safety of sorafenib in a neoadjuvant setting for HCC awaiting liver transplantation (LT) are heterogeneous and scarce. We aimed to investigate the trajectory of patients treated with sorafenib while awaiting LT. All patients listed for HCC and treated with sorafenib were included in a monocentric observational study.

Morbid obesity increases death and dropout from the liver transplantation waiting list: A prospective cohort study.

Unlabelled: Liver transplant (LT) candidates with a body mass index (BMI) over 40 kg/m have lower access to a liver graft without clear explanation. Thus, we studied the impact of obesity on the waiting list (WL) and aimed to explore graft proposals and refusal.

Method: Data between January 2007 and December 2017 were extracted from the French prospective national database: CRISTAL.

Subclinical proximal tubulopathy in hepatitis B: The roles of nucleot(s)ide analogue treatment and the hepatitis B virus.

Background: The recommended monitoring tools for evaluating nucleot(s)ide analogue renal toxicity, such as estimated glomerular filtration rate (eGFR) and phosphatemia, are late markers of proximal tubulopathy. Multiple early markers are available, but no consensus exists on their use.

Aim: To determine the 24 mo prevalence of subclinical proximal tubulopathy (SPT), as defined with early biomarkers, in treated untreated hepatitis B virus (HBV)-monoinfected patients.

Real life experience of mycophenolate mofetil monotherapy in liver transplant patients.

Background: Mycophenolate mofetil (MMF) monotherapy following liver transplantation (LT) remains controversial due to a risk of acute rejection. The aim of this study was to report the largest multicenter experience of the use a MMF monotherapy guided by therapeutic drug monitoring using pharmacoslope modeling and Bayesian estimations of the MPA inter-dose AUC (AUC) before withdrawing calcineurin inhibitors (CNI) and to evaluate the benefit of MMF monotherapy.

Methods: MMF daily doses were adjusted to reach the AUC target of 45μg.

Comparison of the effect of direct-acting antiviral with and without ribavirin on cyclosporine and tacrolimus clearance values: results from the ANRS CO23 CUPILT cohort.

Purpose: Direct-acting antiviral agents have demonstrated their efficacy in treating HCV recurrence after liver transplantation and particularly the sofosbuvir/daclatasvir combination. Pharmacokinetic data on both calcineurin inhibitors and direct-acting antiviral exposure in liver transplant recipients remain sparse.

Methods: Patients were enrolled from the ANRS CO23 CUPILT cohort.

Quality of life in patients with chronic hepatitis C infection: Severe comorbidities and disease perception matter more than liver-disease stage.

Background And Aims: This study evaluated the clinical and non-clinical determinants of health-related quality of life (HRQoL) associated with untreated chronic hepatitis C (CHC) in France.

Methods: From 01/2014 to 01/2015, untreated CHC patients were invited to complete a questionnaire including EQ-5D utility instrument and two visual analogue scales (VAS) measuring overall health and fatigue in three French centers (Paris, Lille and Montpellier). Answers were analyzed in mixed models (taking into account the clustering effects of centers and physicians).

Assessing the cost-effectiveness of hepatitis C screening strategies in France.

Background & Aims: In Europe, hepatitis C virus (HCV) screening still targets people at high risk of infection. We aim to determine the cost-effectiveness of expanded HCV screening in France.

Methods: A Markov model simulated chronic hepatitis C (CHC) prevalence, incidence of events, quality-adjusted life years (QALYs), costs and incremental cost-effectiveness ratio (ICER) in the French general population, aged 18 to 80 years, undiagnosed for CHC for different strategies: S1 = current strategy targeting the at risk population; S2 = S1 and all men between 18 and 59 years; S3 = S1 and all individuals between 40 and 59 years; S4 = S1 and all individuals between 40 and 80 years; S5 = all individuals between 18 and 80 years (universal screening).

Grazoprevir plus elbasvir in HCV genotype-1 or -4 infected patients with stage 4/5 severe chronic kidney disease is safe and effective.

Patients with advanced chronic kidney disease who receive direct-acting antiviral drugs require special consideration regarding comorbid conditions. Here we assessed the efficacy and safety of grazoprevir plus elbasvir in 93 patients infected with HCV genotype 1 or 4 and with advanced chronic kidney disease in a non-randomized, multicenter, nationwide observational survey. Twenty patients with HCV genotype 1a, 51 patients with 1b, four unclassified genotype 1, 17 with genotype 4 and one with genotype 6 received grazoprevir plus elbasvir (100/50 mg) once daily.

Safety of sofosbuvir-based regimens after liver transplantation: longitudinal assessment of renal function in the prospective ANRS CO23 CUPILT study.

Background: In liver transplant recipients with hepatitis C virus recurrence, there is concern about renal safety of sofosbuvir-based regimens. Changes in serum creatinine or in the estimated glomerular filtration rate (eGFR) under treatment are used to look for possible renal toxicity. However, serum creatinine and eGFR are highly variable.

12 Weeks of a Ribavirin-Free Sofosbuvir and Nonstructural Protein 5A Inhibitor Regimen Is Enough to Treat Recurrence of Hepatitis C After Liver Transplantation.

Unlabelled: Sofosbuvir (SOF) combined with nonstructural protein 5A (NS5A) inhibitors has demonstrated its efficacy in treating a recurrence of hepatitis C virus (HCV) after liver transplantation (LT). However, the duration of treatment and need for ribavirin (RBV) remain unclear in this population. Our aim was to determine whether LT recipients could be treated with an SOF + NS5A inhibitor-based regimen without RBV for 12 weeks post-LT.

Very slow decline of hepatitis B virus surface antigen and core related antigen in chronic hepatitis B patients successfully treated with nucleos(t)ide analogues.

We investigated the decline of hepatitis B virus surface antigen (HBsAg) and core related antigen (HBcrAg) in chronic hepatitis B patients sussessfully treated with nucleos(t)ide analogues. In patients with plasma viral suppression, the baseline median levels of HBsAg and HBcrAg were 3.1 and 3.

Sanger sequencing versus INNO-LiPA® HBV PreCore assay for routine detection of precore and basal core promoter mutations in hepatitis virus B chronically infected patients.

We compared the Sanger sequencing and the commercial INNO-LiPA® HBV assay for the routine detection of precore (PC) and basal core promoter (BCP) mutations of hepatitis B virus in chronically infected patients. The overall agreement rate between assays was 94.2% and 98.

Efficacy of daclatasvir-based quadruple therapy in nonresponder patients infected by hepatitis C virus genotype 4: the ANRS HC32 QUATTRO study.

Background: A few direct antiviral agents have been studied in difficult-to-treat patients infected by hepatitis C virus (HCV) genotype 4 (GT4). The efficacy of daclatasvir (DCV), asunaprevir (ASV), pegylated interferon and ribavirin (Peg-IFN/RBV) association was investigated in these patients.

Patients And Methods: This open-label, single-arm, phase 2 study was conducted in HCV GT4 patients who were null or partial responders to Peg-IFN/RBV.

Direct-acting antiviral agent-based regimen for HCV recurrence after combined liver-kidney transplantation: Results from the ANRS CO23 CUPILT study.

Hepatitis C virus (HCV) infection is associated with reduced patient survival following combined liver-kidney transplantation (LKT). The aim of this study was to assess the efficacy and safety of second-generation direct-acting antivirals (DAAs) in this difficult-to-treat population. The ANRS CO23 "Compassionate use of Protease Inhibitors in Viral C Liver Transplantation" (CUPILT) study is a prospective cohort including transplant recipients with recurrent HCV infection treated with DAAs.

Sofosbuvir-Based Regimens in HIV/HCV Coinfected Patients After Liver Transplantation: Results From the ANRS CO23 CUPILT Study.

Background: A recurrence of hepatitis C virus (HCV) after liver transplantation affects survival in human immunodeficiency virus (HIV)/HCV coinfected patients. This study assessed the efficacy and safety of sofosbuvir (SOF)-based regimens in HIV/HCV coinfected patients after liver transplantation.

Methods: Twenty-nine HIV/HCV coinfected transplanted patients receiving tacrolimus-, cyclosporine-, or everolimus-based immunosuppressive therapy were enrolled in the Compassionate Use of Protease Inhibitors in Viral C Liver Transplantation cohort.

Efficacy and safety of boceprevir-based triple therapy in HCV cirrhotic patients awaiting liver transplantation (ANRS HC29 BOCEPRETRANSPLANT).

Background And Aims: In this French multicentre, open-label study, we analyzed the efficacy, safety and patient-reported outcomes of a boceprevir-based triple therapy in HCV genotype 1 cirrhotic patients awaiting liver transplantation (LT).

Methods: Patients received PEG-IFN/ribavirin (RBV) for 48 weeks (W) and boceprevir from W4 to W48 or until LT.

Results: Fifty-one patients (80% males, median age: 56 years) were included.

Sofosbuvir-based treatment of hepatitis C with severe fibrosis (METAVIR F3/F4) after liver transplantation.

Recurrence of hepatitis C virus (HCV) after liver transplantation (LT) can rapidly lead to liver graft cirrhosis and, therefore, graft failure and retransplantation or death. The aim of the present study was to assess efficacy and tolerance of sofosbuvir (SOF)-based regimens for the treatment of HCV recurrence in patients with severe fibrosis after LT. The Compassionate Use of Protease Inhibitors in Viral C Liver Transplantation (CULPIT) study is a prospective multicenter cohort including patients with HCV recurrence following LT treated with second generation direct antivirals.

Multicentre experience using daclatasvir and sofosbuvir to treat hepatitis C recurrence - The ANRS CUPILT study.

Background & Aims: HCV recurrence remains a major issue in the liver transplant field, as it has a negative impact on both graft and patient survival. The purpose of this study was to investigate the efficacy and safety of treating HCV recurrence with sofosbuvir (SOF) and daclatasvir (DCV) combination therapy.

Methods: From October 2013 to March 2015, 559 liver recipients were enrolled in the prospective multicentre France REcherche Nord&Sud Sida-hiv Hépatites (ANRS) Compassionate use of Protease Inhibitors in viral C Liver Transplantation cohort.

[Hepatitis B and pregnancy. Part 2. Nine practical issues about delivery and neonatal care].

In France, the hepatitis B maternal-fetal transmission prevention strategy is based on serovaccination at birth. Serum therapy is to inject 30IU/kg of anti-HBs specific immunoglobulins of human origin in the first hours of life, which in practice corresponds to 1ml or 100IU. Vaccination should also be performed during the first hours of life, and a new injection should be performed at 1month and 6months.

Cost-effectiveness and budget impact of interferon-free direct-acting antiviral-based regimens for hepatitis C treatment: the French case.

We evaluated the cost-effectiveness and the budget impact of new DAA-based regimen use in France. A Markov model simulated chronic hepatitis C (CHC) treatment interventions with IFN-based and IFN-free regimens at stage of fibrosis ≥F3, ≥F2 or regardless of fibrosis stage, and treatment either with the least or the most expensive combination. It estimated quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs).

[Hepatitis B and pregnancy. Part 1. Thirteen practical issues in antenatal period].

In France, the prevalence of chronic hepatitis B is about 1% in pregnant women (usually asymptomatic carriers of HBsAg). The risk of maternal-fetal transmission of hepatitis B is particularly high when viral load measured by PCR is higher in mothers (above 7 log) or HBeAg is present. In case of maternal-fetal transmission of hepatitis B, the risk to the newborn of developing subsequent chronic hepatitis B is very high (90%), with long-term complications such as cirrhosis and hepatocellular carcinoma.

The CUPIC algorithm: an accurate model for the prediction of sustained viral response under telaprevir or boceprevir triple therapy in cirrhotic patients.

Triple therapy using boceprevir or telaprevir remains the reference treatment for genotype 1 chronic hepatitis C in countries where new interferon-free regimens have not yet become available. Antiviral treatment is highly required in cirrhotic patients, but they represent a difficult-to-treat population. We aimed to develop a simple algorithm for the prediction of sustained viral response (SVR) in cirrhotic patients treated with triple therapy.

Drug-Eluting Beads Loaded With Doxorubicin (DEBDOX) Chemoembolisation Before Liver Transplantation for Hepatocellular Carcinoma: An Imaging/Histologic Correlation Study.

Purpose: Most transplant centers use chemoembolisation as locoregional bridge therapy for hepatocellular carcinoma (HCC) before liver transplantation (LT). Chemoembolisation using beads loaded with doxorubicin (DEBDOX) is a promising technique that enables delivery of a large quantity of drugs against HCC. We sought to assess the imaging-histologic correlation after DEBDOX chemoembolisation.

Effectiveness of telaprevir or boceprevir in treatment-experienced patients with HCV genotype 1 infection and cirrhosis.

Background & Aims: We investigated the effectiveness of the protease inhibitors peginterferon and ribavirin in treatment-experienced patients with hepatitis C virus (HCV) genotype 1 infection and cirrhosis.

Methods: In the Compassionate Use of Protease Inhibitors in Viral C Cirrhosis study, 511 patients with HCV genotype 1 infection and compensated cirrhosis who did not respond to a prior course of peginterferon and ribavirin (44.3% relapsers or patients with viral breakthrough, 44.

Should we await IFN-free regimens to treat HCV genotype 1 treatment-naive patients? A cost-effectiveness analysis (ANRS 95141).

Background & Aims: In treatment-naive patients mono-infected with genotype 1 chronic HCV, treatments with telaprevir/boceprevir (TVR/BOC)-based triple therapy are standard-of-care. However, more efficacious direct-acting antivirals (IFN-based new DAAs) are available and interferon-free (IFN-free) regimens are imminent (2015).

Methods: A mathematical model estimated quality-adjusted life years, cost and incremental cost-effectiveness ratios of (i) IFN-based new DAAs vs.