Second-line therapy for advanced hepatocellular carcinoma with regorafenib or cabozantinib: Multicenter French clinical experience in real-life after matching.

Background: Starting a second-line systemic treatment for hepatocellular carcinoma (HCC) is a common situation. The only therapeutic options in France are two broad-spectrum tyrosine kinase inhibitors (TKIs), regorafenib (REG) and cabozantinib (CBZ), but no comparative real-life studies are available.

Aim: To evaluate the progression-free survival (PFS) of patients treated with REG or CBZ, we investigated the disease control rate (DCR), overall survival (OS), and safety of both drugs.

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

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.

Hepatitis C virus infection impacts work productivity and fatigue: An epidemiologic real-life study.

Introduction And Objective: Hepatitis C virus (HCV) infection and treatment impact the patient's daily life and work productivity. Until recently, treatments were associated with side effects and insufficient virologic and hepatic results. This study evaluated fatigue, work productivity, and treatment modalities in patients with HCV infection.

Long-term Efficacy of Interferon-Free Antiviral Treatment Regimens in Patients With Hepatitis C Virus-Associated Cryoglobulinemia Vasculitis.

Background & Aims: In small-size and short-term studies of hepatitis C virus-associated cryoglobulinemia vasculitis (HCV-CryoVas), patients had a higher rate of response and tolerance to direct-acting antiviral (DAA) agents than interferon-containing regimens. We collected follow-up data from a clinical trial to determine the long-term effectiveness and tolerance of all-oral, interferon-free DAA regimens in patients with CryoVas.

Methods: We collected follow-up data from a prospective international multicenter cohort study of 148 patients with symptomatic HCV-CryoVas (53.

Safety and efficacy of intra-arterial hepatic chemotherapy with doxorubicin-loaded nanoparticles in hepatocellular carcinoma.

Background: Doxorubicin Transdrug (DT), a nanoformulation of doxorubicin, was demonstrated to overcome the chemoresistance of hepatocellular carcinoma (HCC) in preclinical models. Its efficacy and safety were thus investigated in phase I and randomised phase II trials in unresectable HCC.

Patients And Methods: Phase I was a single dose of DT through the hepatic intra-arterial (HIA) route, dose-escalating 3+3 trial, evaluating five-dose levels from 10 to 40 mg/m with maximal tolerated dose (MTD) as primary endpoint.

Efficacy and Safety of Sofosbuvir Plus Daclatasvir for Treatment of HCV-Associated Cryoglobulinemia Vasculitis.

Circulating mixed cryoglobulins are detected in 40%-60% of patients with hepatitis C virus (HCV) infection, and overt cryoglobulinemia vasculitis (CryoVas) develops in approximately 15% of patients. Remission of vasculitis has been associated with viral clearance, but few studies have reported the effectiveness of direct-acting antiviral drugs in these patients. We performed an open-label, prospective, multicenter study of the effectiveness and tolerance of an all-oral, interferon- and ribavirin-free regimen of sofosbuvir plus daclatasvir in patients with HCV-associated CryoVas.

Direct-Acting Antiviral Therapy Restores Immune Tolerance to Patients With Hepatitis C Virus-Induced Cryoglobulinemia Vasculitis.

Background & Aims: Interferon-free direct-acting antiviral (DAA) therapies are effective in patients with hepatitis C virus-induced cryoglobulinemia vasculitis (HCV-CV). We analyzed blood samples from patients with HCV-CV before and after DAA therapy to determine mechanisms of these drugs and their effects on cellular immunity.

Methods: We performed a prospective study of 27 consecutive patients with HCV-CV (median age, 59 y) treated with DAA therapy (21 patients received sofosbuvir plus ribavirin for 24 weeks, 4 patients received sofosbuvir plus daclatasvir for 12 weeks, and 2 patients received sofosbuvir plus simeprevir for 12 weeks) in Paris, France.

Sofosbuvir plus ribavirin for hepatitis C virus-associated cryoglobulinaemia vasculitis: VASCUVALDIC study.

Background: Hepatitis C virus (HCV) is the aetiological agent for most cases of cryoglobulinaemia vasculitis. Interferon-containing regimens are associated with important side effects and may exacerbate the vasculitis.

Objective: To evaluate safety and efficacy of an oral interferon-free regimen, sofosbuvir plus ribavirin, in HCV-cryoglobulinaemia vasculitis.

FIG4 is a hepatitis C virus particle-bound protein implicated in virion morphogenesis and infectivity with cholesteryl ester modulation potential.

There is growing evidence that virus particles also contain host cell proteins, which provide viruses with certain properties required for entry and release. A proteomic analysis performed on double-gradient-purified hepatitis C virus (HCV) from two highly viraemic patients identified the phosphatidylinositol 3,5-bisphosphate 5-phosphatase FIG4 (KIAA0274) as part of the viral particles. We validated the association using immunoelectron microscopy, immunoprecipitation and neutralization assays in vitro as well as patient-derived virus particles.

Impact of lamivudine-resistance mutations on entecavir treatment outcome in hepatitis B.

Background And Objective: Entecavir (ETV) is a potent inhibitor of viral replication in nucleos(t)ide analog (NA)-naive chronic hepatitis B patients with a very low rate of resistance (≤1.2%) over 5 years. The aim of this study was to assess the efficacy of ETV treatment in routine clinical practice and to investigate whether persistence of residual viral replication was the result of the emergence and selection of drug-resistant mutants.

Efficacy and tolerance of a combination of tenofovir disoproxil fumarate plus emtricitabine in patients with chronic hepatitis B: a European multicenter study.

Background And Aims: The combination of tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) is used extensively to treat HIV infection and also has potent activity against hepatitis B virus (HBV) infection. The aim of this study was to assess the efficacy and tolerance of TDF + FTC in patients with chronic hepatitis B (CHB).

Methods: Seventy eight consecutive CHB patients from five European centers were included.

Management of nonresponsive hepatitis C.

More than 50% of hepatitis C virus (HCV)-infected patients do not respond to the classical pegylated interferon (PEG-IFN)/ribavirin combination therapy. However, failing to respond to one course of treatment is not synonymous of therapy failure and retreatment is often beneficial. Alternative retreatment strategies include repeating the classical standard of care with an optimized drug regimen and adherence, including ribavirin serum concentration adjustment, correcting, if at all possible, comorbidities, and the addition of new specific anti-HCV molecules to the backbone of pegylated interferon/ribavirin.

End points of therapy in chronic hepatitis B.

This review assesses the relevance of the clinical, histological, biochemical and virological end points in the course and outcome of chronic hepatitis B. The pathway and the impact of the variation in these end points are presented, as well as their definitions. The treatment goals are discussed in terms of quality of life and survival.

Pathobiology of HBV mutants and clinical impact for treatment monitoring.

HBV is the leading cause of liver cancer and frequently leads to cirrhosis and liver failure. The goals of nucleos(t)ide analog treatments are to suppress viral replication to as low as possible, to halt disease progression and to prevent the onset of complications. Due to the mechanism of viral genome persistence, chronic hepatitis B requires long-term therapy that exposes patients to the risk of selection of resistant mutants and treatment failure.

Amantadine triple therapy for non-responder hepatitis C patients. Clues for controversies (ANRS HC 03 BITRI).

Background/aims: To determine whether addition of amantadine to pegylated interferon/ribavirin improved response rates among chronic hepatitis C patients, non-responders to interferon/ribavirin and study the dynamic of response.

Methods: In a double blind, multicenter, randomized trial, 200 non-responder patients received pegylated interferon 1.5 microg/kg per week and ribavirin 800-1200 mg/day, plus either amantadine 200 mg/day or placebo for 48 weeks.

Treatment of chronic hepatitis C in patients unresponsive to interferon. Interest of re-treatment combining interferon induction therapy and ribavirin (a multicenter pilot study).

Aim: About 45% of patients with chronic hepatitis C are unresponsive to the present reference treatment combining pegelated interferon plus ribavirin; before pegylated interferon was available the non-response rate was around 60%. This open multicenter pilot study, initiated before pegylated interferon became available, was designed to evaluate, in patients unresponsive to interferon monotherapy, the rate of biological and virological response and side-effects of the ribivirin-alpha 2b interferon combination.

Methods: The combination protocol was ribavirin (1 to 1.

Disposal of injection material used for the treatment of hepatitis C: comparison with insulin-dependent diabetes and thromboembolism.

Aim: The survey conducted in the Provence-Alpes-Cote d'Azur region in France in 1999 showed that 38% of patients infected with the hepatitis C virus (HCV) receiving interferon injections in their home were aware of the recommendations concerning the disposal of injection material and that 41% of the needles were discarded with household waste after use. The purpose of our study conducted in the Centre region of France was to ascertain how injection material used by HCV-positive patients for interferon treatment are disposed of in comparison with material used by patients injecting insulin for insulin-dependent diabetes mellitus (IDDM) or low-molecular-weight heparin (LMWH) for thromboembolism.

Material And Methods: A questionnaire to be completed by patients was proposed to HCV-positive patients attending hepatogastroenterology clinics in the Centre region hepatitis C network for therapeutic follow-up (N=113 patients) between October 2001-January 2002.

Interferon-alpha 2b plus ribavirin in patients with chronic hepatitis C after liver transplantation: a randomized study.

Background And Aims: Hepatitis C virus (HCV) reinfection after liver transplantation is frequent and leads to chronic hepatitis and cirrhosis. The use of antiviral therapy in this situation remains controversial. This study aimed to assess the safety and efficacy of interferon alfa-2b plus ribavirin for recurrent hepatitis C following liver transplantation.