Implications of Hepatitis B Virus Genomic Variations on Treatment Outcomes

Tai-Chung      Tseng; Chun-Jen      Liu; Jia-Horng      Kao

Abstract

Infection due to hepatitis B virus (HBV) is a global public health issue. With effective treatment, it is possible to prevent disease progression to cirrhosis and hepatocellular carcinoma in chronic hepatitis B patients. Several viral factors have been documented to be associated with disease progression and treatment response, including HBV genotype and several naturally occurring HBV mutants, such as precore stop codon mutation (G1896A) and basal core promoter mutation (A1762T/G1764A). Recent studies suggested that responses to standard interferon or peginterferon are more favourable in patients infected with the HBV virus of genotype A or B than the genotype C or D infection. In contrast, therapeutic responses to nucleos(t)ide analogues are generally comparable between HBV genotypes. In addition to the viral genotype, BCP mutation (A1762T/G1764A) is likely to be associated with a higher sustained viral response in HBeAg-positive patients receiving interferon or peginterferon treatment. In conclusion, therapeutic differences seem to exist among HBV genotypes and genetic variations. However, the definite contribution of each viral factor still remains unclear. Since the majority of current studies included small numbers of patients and were not powered to answer such critical questions, the role of viral genetic variation for treatment outcomes awaits further studies before personalized treatment strategies can be planned.

Keywords: Basal core promoter, genotype, hepatitis B e antigen seroconversion, lamivudine, pegylated interferon, precore stop codon, hepatitis B virus (HBV), cirrhosis, hepatocellular carcinoma, relaxed circular DNA (rcDNA), polymerase, hepatitis B e antigen (HBeAg), pegylated IFN, adefovir dipivoxil, entecavir, tenofovir disoproxil fumarate, HBsAg seroclearance, precore stop codon (PC), basal core promoter (BCP), HBeAg seroconversion, quasispecies, genome-wide association study (GWAS), single nucleotide polymorphisms (SNP), Covalently closed circular DNA, Lamivudine-resistance, Telbivudine, Tyrosine-methionine-aspartate-aspartate