Review on hepatitis B virus precore/core promoter mutations and their correlation with genotypes and liver disease severity

Abstract

Of 350 million people worldwide are chronically infected with hepatitis B virus (HBV) and are at risk of developing cirrhosis and hepatocellular carcinoma (HCC) later in life. HBV is the most diverse DNA virus, and its genome is composed of four open reading frames: Presurface antigen/surface antigen gene (preS/S), precore/core gene (preC/C), polymerase gene (P), and the X gene (X). HBV produces quasispecies naturally or in response to antiviral agents because of the absence of proofreading activity amid reverse transcription and a high replication rate. The virus has 10 genotypes (A to J) with different geographical distributions. There are various HBV mutations in the HBV genome, including preC/C mutations, preS/S mutations, P gene mutations, and X gene mutations. The core promoter region plays a vital part in the replication, morphogenesis and pathogenesis of the virus. The precore region also plays a crucial role in viral replication. Both core promoter and precore mutations rescue the virus from host immune surveillance and result in the formation of mutated strains that may have altered pathogenicity. preC/C mutations are associated with liver disease progression. Precore mutations stop hepatitis B e antigen (HBeAg) production and basal core promoter mutations downregulate HBeAg production. Mutations in the basal core promoter are also associated with increased HBV replication and an increased incidence of advanced liver diseases such as cirrhosis and HCC. The emergence of antiviral-resistant mutations is the main reason for treatment failure. This review focuses mainly on preC/C promoter mutations and their correlation with genotypes and liver disease severity. Thorough perception and knowledge of HBV genetic variety and mutants could be vital to discover techniques for the prognosis and control of HBV infection.

Keywords: Hepatitis B virus; Hepatitis B virus e antigen; Hepatocellular carcinoma; Basal core promoter; Core promoter region; Precore region; Fulminant hepatitis; Acute hepatitis

Core Tip: Worldwide, 350 million people are chronically infected with hepatitis B virus and are at risk for cirrhosis and hepatocellular carcinoma. Both core promoter and precore mutations help rescue the virus from host immune surveillance and result in the formation of mutated strains that may have altered pathogenicity. Precore/core promoter (preC/C) mutations are associated with advanced liver disease. We discuss mainly preC/C mutations and their correlation with genotypes and liver disease severity.