Hepatitis B Virus Genotypes, Mutations and the Risks for Hepatocellular Carcinoma

Abstract

Hepatitis B virus (HBV) has infected more than 400 million people worldwide. HBV infected individuals remaining at increased risk of developing end-stage liver disease including cirrhosis, hepatic failure, and hepatocellular carcinoma (HCC). HCC is the fifth most common cancer worldwide and the third most common cause of cancer mortality. The important risk factors for HCC include the presence of HBV e antigen (HBeAg), a surrogate marker of active viral replication, and the amount of hepatitis B viral load in serum. Recent studies suggest that the genetic characteristics of HBV, including HBV genotype and specific genetic mutations, are associated with the development of HCC [1,2]. HBV is generally classified into four serotypes or subtypes (adr, adw, ayr and ayw) based on antigenic determinants of the hepatitis B surface antigen (HBsAg). These serotypes are further classified into nine subtypes (ayw1-4, ayr, adw2, adw4, adrq+, and adrq-) [3]. The prevalence of these serotypes was found to be varied in different parts of the world. HBV is classified in to 8 genotypes (A-H), based on an intergroup divergence of 8% or more in the complete nucleotide sequence [3]. HBV genotyping methods mainly utilize partial sequence of the HBV genome such as the pre-S or S gene. Advanced molecular biology techniques have revealed significant diversities in sequences of HBV DNA that created allelic differences among the four major HBV serotypes. These genotyping methods include direct sequencing, restriction fragment length polymorphism, line probe assay, and enzyme-linked immunoassay. Recent focus is on the clinically important differences in outcomes that are associated with the different HBV genotypes. Eastern Asia, including Taiwan. HBV genotype C infection has been associated with later occurring and lower rates of spontaneous clearance of HBeAg in serum compared with genotype B [1,2,4,5]. Genotype C is additionally associated with higher levels of HBV DNA replication, more advanced liver disease in general, and a decreased rate of response to interferon therapy compared with genotype B [1,5,6]. The high prevalence of HBV genotypes B and C among Asians raise the possibility that HBV genotype may be related to the endemicity of HBV infection. A study in Switzerland found that genotype A was more common among patients with chronic hepatitis B, whereas genotype D was more prevalent among patients with resolving acute hepatitis B suggesting that HBV genotype A was associated with a higher rate of chronic HBV infection [7]. HBV genotypes may contribute to the wide range in prevalence of HBV infection in different