Implications of Hepatitis B Virus Genomic Variations on Treatment Outcomes

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.

HBeAg‐positive chronic hepatitis B: why do I treat my patients with pegylated interferon?

“…Several common HBV mutant strains such as mutations in the precore (PC), core promoter (CP) and deletion mutations in the pre‐S/S genes have been associated with progressive liver disease, including cirrhosis and HCC , thus their influence on HBV treatment requires further studies. A recent review showed that half of the studies in the literature suggested the PC G1896A mutation or the basal core promoter (BCP) A1762T/G1764A mutation were associated with the response to IFN therapy . A recent study in 115 HBeAg‐positive patients who received PEG‐IFN α‐2a for 6 months indicated that the BCP A1762T/G1764A mutation was associated with a combined response defined as HBeAg seroconversion, HBV DNA levels below 20 000 IU/mL as well as normalization of ALT 6 months after therapy had stopped (OR: 8.04, 95% CI: 2.00–32.28) .…”