Genetic variability of hepatitis B virus and response to antiviral treatments: Searching for a bigger picture

Abstract

Chronic infection with hepatitis B virus (HBV) remains a global public health concern. There are approximately 350 million people in the world who are persistently infected with this virus [1], and they have higher risks of developing complications of the disease that can range from mild to chronic hepatitis to the more advanced disease manifestations which include cirrhosis with hepatic decompensation and hepatocellular carcinoma (HCC). The only means currently to prevent such complications in individuals who are already chronically infected with the virus is to control viral replication and reduce liver damage with the use of interferon-alpha (IFN-a) and or nucleos(t)ide analogs (NA). Nonetheless, efficacies of these treatment methods are limited, and there is increasing evidence to suggest that these limitations are associated with the genetic variability of HBV [2–4]. The HBV genome is complex and has at least four open reading frames (ORF) that overlap one another so that the total coding capacity is around one and a half times the genomic length. This viral family is classified into eight geographically defined genotypes (A to H) based on P8% diversity of their entire genome nucleotide sequences. HBV genotypes have significant associa-