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.

Sorafenib: Experience and Better Manage-ment of Side Effects Improve Overall Survival in Hepatocellular Carcinoma Patients: A Real-Life Retrospective Analysis.

Background: Sorafenib is the first-line treatment for advanced hepatocellular carcinoma (HCC). The management of its side effects is improving. This study aimed to assess, in real life, if this translates into a better prognosis.

Hepatocellular carcinoma macroscopic gross appearance on imaging: predictor of outcome after transarterial chemoembolization in a real-life multicenter French cohort.

Background: Conventional transarterial chemoembolization (cTACE) with lipiodol is widely performed in patients with hepatocellular carcinoma (HCC) unsuitable for curative treatment. Additional tumor parameters such as HCC macroscopic appearance based on imaging might be helpful for transarterial chemoembolization prognostication and management.

Patients And Methods: A total of 405 patients with HCC who underwent cTACE between 2008 and 2016 from a real-life multicenter French cohort were retrospectively reviewed.

[Hepatitis B virus infection: control or cure?].

Hepatitis b virus infection: control or cure? Hepatitis B virus infection remains a global public health issue with changing epidemiology due to several factors including vaccination policies and migration. Approximately 254 million individuals are chronic HBsAg carrier worldwide including around 300 000 individuals in France. Host immune response plays a key role in hepatitis B pathogenesis and clinical manifestations.

Sofosbuvir, velpatasvir and voxilaprevir: a new triple combination for hepatitis C virus treatment. One pill fits all? Is it the end of the road?

The advent of oral direct-acting antiviral agents (DAAs) has dramatically improved the hepatitis C virus (HCV) treatment landscape in the last 4 years, providing cure rates over 95% with a shorter duration of treatment and a very good safety profile. This has enabled access to treatment in nearly all HCV infected patients. The launch of two pangenotypic fixed dose combinations (FDCs) in 2017 made a new step forward in HCV treatment by slightly increasing efficacy and more importantly allowing the treatment of patients without HCV genotyping, and in some cases without fibrosis assessment.

Hepatocellular carcinoma recurrence in hepatitis C virus-related cirrhosis treated with direct-acting antivirals: a case-control study.

Background: Direct-acting antivirals (DAAs) therapy against hepatitis C viral (HCV) infection has markedly improved the sustained viral response. However, recent studies have suggested an unsuspected high rate of hepatocellular carcinoma (HCC) recurrence.

Patients And Methods: A retrospective case-control study was carried out to investigate the impact of DAAs on tumor recurrence in patients with complete response to HCC treatment within our HCV-related cirrhosis cohort.

Clinical relevance of the HCV protease inhibitor-resistant mutant viral load assessed by ultra-deep pyrosequencing in treatment failure.

Background: The detection of low frequency mutants in patients with hepatitis C virus (HCV) receiving direct-acting antivirals (DAAs) is still debated. The clinical relevance of the mutant viral load has not yet been evaluated.

Objectives: To assess the viral load of resistance associated variants (RAVs) in patients at different time points, including the baseline, virological failure and one year after the cessation of therapy.

Sofosbuvir plus ledipasvir in combination for the treatment of hepatitis C infection.

Sofsobuvir is the first-in-class NS5B nucleotide inhibitor to be launched as a treatment for the hepatitis C virus (HCV). Its viral potency, pan genotypic activity and high barrier to resistance make it the ideal candidate to become a backbone for several IFN-free regimens. Ledipasvir is a NS5A inhibitor with multi genotypic activity but modest barrier to resistance.

Sofosbuvir as backbone of interferon free treatments.

Sofosbuvir is the first-in-class NS5B nucleotide analogues to be launched for hepatitis C virus (HCV) treatment. Its viral potency, pangenotypic activity and high barrier to resistance make it the ideal candidate to become a backbone for several IFN-free regimens. Recent data demonstrated that sofosbuvir either with ribavirin alone or in combination with other direct-acting antivirals (DAAs) as daclatasvir, ledipasvir or simeprevir are able to cure HCV in at least 90% or over of patients.

Chronic hepatitis C: future treatment.

The launch of first-generation protease inhibitors (PIs) is a major step forward in HCV treatment. However, the major advance is up to now restricted to genotype 1 (GT-1) patients. The development of second-wave and second-generation PIs yields higher antiviral potency through plurigenotypic activity, more convenient daily administration, fewer side effects and, for the second-generation PIs, potential activity against resistance-associated variants.

How to optimize current therapy of HCV genotype 1 infection with boceprevir.

Treatment with first generation protease inhibitors (PIs) is a milestone in the history of HCV therapy. Triple therapy with boceprevir (BOC) improves sustained virological response (SVR) by 30% in treatment naïve genotype 1 patients and by 50-60% in relapsers, 40-45% in partial responders and 25% in null responders compared with the Pegylated Interferon (PEG-IFN) and ribavirin regimen. To optimize BOC treatment, screening and access to treatment must be improved in genotype 1 patients.

Detection of IL28B SNP DNA from buccal epithelial cells, small amounts of serum, and dried blood spots.

Background & Aims: Point mutations in the coding region of the interleukin 28 gene (rs12979860) have recently been identified for predicting the outcome of treatment of hepatitis C virus infection. This polymorphism detection was based on whole blood DNA extraction. Alternatively, DNA for genetic diagnosis has been derived from buccal epithelial cells (BEC), dried blood spots (DBS), and genomic DNA from serum.

Chronic hepatitis C: treatments of the future.

The launch of first-generation protease inhibitors (PIs) was a major step forward in hepatitis C virus (HCV) treatment. However, this major advance has, up to now, only been applicable to genotype-1 patients. Second-wave and second-generation PIs appear to achieve higher antiviral potency, with pan-genotype activities, fewer side-effects and potential activity against PI-resistant mutation by second-generation PIs, through more convenient daily administration.

Future treatment of patients with HCV cirrhosis.

Of all hepatitis C virus (HCV) patients, those with cirrhosis are most in need of treatment because of increased morbidity and mortality. Treatment with pegylated-interferon (PEG-IFN) and ribavirin (RBV) (PR) has definitely shown the benefits of successful treatment by improving fibrosis, causing the regression of cirrhosis and reducing and preventing cirrhosis-related complications. However, the sustained virological response (SVR) is lower in patients with cirrhosis.

A single IL28B genotype SNP rs12979860 determination predicts treatment response in patients with chronic hepatitis C Genotype 1 virus.

Background: Recent studies have suggested that host genetics may be useful for predicting drug response and have supported the recommendation that single polynucleotide polymorphisms (SNPs) of IL28B should be investigated when treating hepatitis C virus (HCV)-1 infected patients. The aim of this study was to determine whether a single IL-28B genotype SNP rs8099917 or rs12979860 determination is sufficient to predict treatment failure in patients with chronic HCV.

Methods: A total of 198 patients were included; mean (±standard deviation) age was 47±12 years and 140 (71%) were men.

Occult hepatitis C virus infection revisited with ultrasensitive real-time PCR assay.

Occult hepatitis C infection is regarded as a new entity that should be considered when diagnosing patients with a liver disease of unknown origin. Using an ultrasensitive real-time PCR assay, we demonstrated that occult hepatitis C virus (HCV) infection cannot be found in peripheral blood mononuclear cells of patients with cryptogenic liver diseases, HCV--associated systemic vasculitis, or connective tissue diseases. The significance of such occult infection must be elucidated.

High predictive value of early viral kinetics in retreatment with peginterferon and ribavirin of chronic hepatitis C patients non-responders to standard combination therapy.

Background/aims: To evaluate the efficacy of peginterferon alfa-2b and ribavirin in unselected consecutive patients with chronic hepatitis C, treated outside of trials, who were relapsers or non-responders to interferon and ribavirin combination.

Methods: One hundred and fifty-four patients were evaluated. There were 101 non-responders and 53 relapsers to standard combination therapy.

Diagnostic and predictive factors of significant liver fibrosis and minimal lesions in patients with persistent unexplained elevated transaminases. A prospective multicenter study.

Background/aims: In patients with unexplained elevated transaminases, prognosis of the liver disease and factors associated with increased risk of liver fibrosis and normal/subnormal liver are unknown. The aim of this prospective study was to identify diagnosis and clinical and biological factors associated with significant (bridging) fibrosis and minimal lesions of the liver in patients with persistent unexplained elevated ALT levels.

Methods: From July 2002 through October 2004, all consecutive asymptomatic patients with unexplained chronically elevated ALT levels were included.

[Sarcoidosis following pegylated interferon therapy: two cases].

One side effect of the immunomodulatory effect of interferon is the possible triggering or exacerbation of systemic or cutaneous sarcoidosis. We report two new cases and offer an exhaustive review of the literature. A 39-year-old man with type C chronic active hepatitis developed new respiratory symptoms and pulmonary infiltrates with hilar and mediastinal adenopathy after 7 months of treatment with pegylated interferon.