Scripps Research Logo

Welcome to the Gallay Laboratory

Viral Hepatitis and Liver Diseases Overview

Click here for Human Immunodeficiency Virus-1 (HIV-1) Cure Overview

About 240 and 71 million people suffer from chronic HBV (CHB) and chronic HCV infection (CHV), respectively. CHB and CHV infections represent the leading cause for hepatocellular carcinoma (HCC) (70%). HCC carries high economic burden on society. The risk of developing HCC is 20-fold higher in CHB compared to non-infected controls, and up to 17-fold increase in CHV-associated liver cirrhosis. Owing to the high risk of developing end-stage liver disease or HCC, CHB is associated with high mortality (15-40% in 10-25 years), with 880,000 deaths per year. Similarly, 500,000 people die each year from CHV-related liver diseases such as liver cirrhosis or HCC. HBV initiates the neoplastic process while HCV acts as a promoter having a synergistic effect in causing HCC. The risk for HCC in CHB and CHC is linked to liver inflammation that drives fibrosis, cirrhosis and HCC. It is the persistent inflammation and destruction of hepatocytes that leads to carcinogenesis. The risk of HCC development remains after virus elimination, especially for patients who had advanced liver cirrhosis at the time of treatment. More than 100 trials evaluating chemotherapy or targeted therapies in HCC failed to show survival advantage. Thus, it is of the utmost importance to identify novel therapeutic approaches to treat viral hepatitis-induced HCC.

Recently our lab identified a novel class of small and safe compounds called cyclophilin inhibitors (CypI) including CRV431, NV556 and Alisporivir, which possess dual therapeutic activities critical for preventing the development of viral hepatitis-induced HCC. We reported that CypI inhibit HCV and HBV replication in vitro and in vivo, but also discovered that CypI inhibit the development of non-alcoholic steatohepatitis (NASH), liver fibrosis and HCC in several liver diseases mouse models that we developed in the lab.

 Viral Hepatitis and Liver Diseases 1

Viral Hepatitis and Liver Diseases 2