Pharmacotherapy of chronic viral hepatitis and hepatocellular carcinoma.

Background: Hepatitis B virus (HBV) is a major etiologic agent of chronic liver disease (CLD) and hepatocellular carcinoma. Drugs have been developed and shown to be effective against HBV replication. These treatments are often associated with the resolution of CLD. However, they are too expensive, not well tolerated, and result in the development of resistance when given as mono or salvage therapies. In addition, most of these drugs target only the virus polymerase.

Objective: To revitalize the field, drugs with other targets and combination therapies need to be developed.

Methods: Major advances in HBV and liver cancer drug development over the past decade, focusing on Phase III trials and FDA-approved compounds, are presented.

Results/discussion: A number of potent nucleoside/nucleotide analogs are now available for treatment, but for the long-term management of CLD, the development of combination therapies will probably be required. Development of compounds with new virus targets will enhance the utility of combination therapies. Development of compounds to host targets altered prior to or after the development of liver cancer, as demonstrated by sorafenib, need to be developed. The goal is to devise drug cocktails that will yield sustained virus responses and halt disease progression and tumor development.