Clinical implications of hepatitis B virus mutations: Recent advances

Abstract

Hepatitis B virus (HBV) infection is a major cause of acute and chronic hepatitis, and of its long-term complications. It is the most variable among DNA viruses, mostly because of its unique life cycle which includes the activity of error-prone enzyme, reverse transcriptase, and the very high virion production per day. In last two decades, numerous research studies have shown that the speed of disease progression, reliability of diagnostic methods and the success of antiviral therapy and immunization are all influenced by genetic variability of this virus. It was shown that mutations in specific regions of HBV genome could be responsible for unwanted clinical outcomes or evasion of detection by diagnostic tools, thus making the monitoring for these mutations a necessity in proper evaluation of patients. The success of the vaccination programs has now been challenged by the discovery of mutant viruses showing amino acid substitutions in hepatitis B surface antigen (HBsAg), which may lead to evasion of vaccine-induced immunity. However, the emergence of these mutations has not yet raised concern since it was shown that they develop slowly. Investigations of HBV genetic variability and clinical implications of specific mutations have resulted in significant advances over the past decade, particularly in regard to management of resistance to antiviral drugs. In the era of drugs with high genetic barrier for resistance, on-going monitoring for possible resistance is still essential since prolonged therapy is often necessary. Understanding the frequencies and clinical implications of viral mutations may contribute to improvement of diagnostic procedures, more proper planning of immunization programs and creating the most efficient therapeutic protocols.

Keywords: Hepatitis B virus; Hepatitis B virus variability; Mutation; Drug resistance; Vaccine escape

Core tip: Understanding the frequencies and clinical implications of Hepatitis B virus (HBV) mutations may contribute to improvement of diagnostic procedures, more proper planning of immunization programs and creating the most efficient therapeutic protocols. This paper brings an overview and latest research results on the most important, clinically relevant, HBV mutations. The covered topics include mutations involved in vaccine-escape phenomenon, resistance to currently available antiviral drugs, development of “occult” hepatitis, hepatocellular carcinoma, fulminant hepatitis and hepatitis B e antigen-negative hepatitis, as well as the problem of these mutations in HBV/human immunodeficiency virus and HBV/hepatitis C virus co-infected patients.