Guidance for design and endpoints of clinical trials in chronic hepatitis B - Report from the 2019 EASL-AASLD HBV Treatment Endpoints Conference.

Representatives from academia, industry, regulatory agencies, and patient groups convened in March 2019 with the primary goal of developing agreement on chronic HBV treatment endpoints to guide clinical trials aiming to 'cure' HBV. Agreement among the conference participants was reached on some key points. 'Functional' but not sterilising cure is achievable and should be defined as sustained HBsAg loss in addition to undetectable HBV DNA 6 months post-treatment.

Guidance for design and endpoints of clinical trials in chronic hepatitis B - Report from the 2019 EASL-AASLD HBV Treatment Endpoints Conference.

Representatives from academia, industry, regulatory agencies, and patient groups convened in March 2019 with the primary goal of developing agreement on chronic hepatitis B virus (HBV) treatment endpoints to guide clinical trials aiming to 'cure' HBV. Agreement among the conference participants was reached on some key points. 'Functional' but not sterilizing cure is achievable and should be defined as sustained HBsAg loss in addition to undetectable HBV DNA 6 months post-treatment.

Hepatitis B Treatment: What We Know Now and What Remains to Be Researched.

Chronic hepatitis B virus (HBV) infection remains a major global health burden. Currently, two types of treatment, interferons (IFNs) and nucleos(t)ide analogues (NAs), have been approved. These treatments are effective in suppressing HBV replication and in decreasing the risk of developing cirrhosis, liver failure, hepatocellular carcinoma (HCC), and death.

Characteristics of adults in the hepatitis B research network in North America reflect their country of origin and hepatitis B virus genotype.

Background & Aims: Chronic hepatitis B virus (HBV) infection is an important cause of cirrhosis and hepatocellular carcinoma worldwide; populations that migrate to the United States and Canada might be affected disproportionately. The Hepatitis B Research Network (HBRN) is a cooperative network of investigators from the United States and Canada, created to facilitate clinical, therapeutic, and translational research in adults and children with hepatitis B. We describe the structure of the network and baseline characteristics of adults with hepatitis B enrolled in the network.

HCV NS5A inhibitors in development.

NS5A protein plays a key role in hepatitis C virus (HCV) replication. Daclatasvir (DCV, BMS-790052) is a first-in-class inhibitor of the HCV NS5A replication complex with potent antiviral activity but a low barrier to resistance. DCV as triple therapy in combination with pegylated interferon and ribavirin resulted in a high rate of early virologic response in treatment-naïve patients with genotype 1 infection; as quadruple therapy in combination with asunaprevir (BMS-650032, NS3 protease inhibitor), pegylated interferon, and ribavirin, it resulted in a high rate of sustained virologic response in genotype 1 prior null responders.

Does antiviral therapy for hepatitis B and C prevent hepatocellular carcinoma?

Approximately 75% to 80% of hepatocellular carcinomas (HCC) worldwide are attributed to chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) infection. Thus, effective prevention of HBV and HCV infection and progression from acute HBV and HCV infection to chronic hepatitis, cirrhosis and HCC might prevent as many as 450,000 deaths from HCC each year. The most effective approach to preventing HCC is to prevent HBV and HCV infection through vaccination.

Antiviral therapy for chronic hepatitis B.

The goal of antiviral therapy for chronic hepatitis B is to prevent the development of cirrhosis and hepatocellular carcinoma. End points, including viral suppression, alanine aminotransferase normalization, hepatitis B e antigen loss, hepatitis B surface antigen loss, and improvement in liver histology, are used to determine treatment success. Treatment is based on hepatitis B virus (HBV) replication status and stage of liver disease, modulated by the age of the patient, hepatitis B e antigen (HBeAg) status and patient preference.

Characterization of genotype-specific carboxyl-terminal cleavage sites of hepatitis B virus e antigen precursor and identification of furin as the candidate enzyme.

Hepatitis B e antigen (HBeAg) is a secreted version of hepatitis B virus (HBV) core protein that promotes immune tolerance and persistent infection. It is derived from a translation product of the precore/core gene by two proteolytic cleavage events: removal of the amino-terminal signal peptide and removal of the carboxyl-terminal arginine-rich sequence. Four RXXR motifs are present at the carboxyl terminus of the HBeAg precursor, with the first two fused as (151)RRGRSPR(157).

Natural history of chronic hepatitis B virus infection: what we knew in 1981 and what we know in 2005.

Remarkable progress has been made in our understanding of the natural history of chronic hepatitis B virus (HBV) infection in the past 25 years. Availability of sensitive HBV DNA assays and application of sophisticated immunological techniques led to the recognition that HBV replication persists throughout the course of chronic HBV infection, and host immune response plays a pivotal role in HBV-related liver disease. Knowledge of the HBV genome organization and replication cycle led to the unraveling of HBV genotypes and molecular variants, which contribute to the heterogeneity in outcome of chronic HBV infection.