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Review
. 2015 May 1;5(5):a021436.
doi: 10.1101/cshperspect.a021436.

Hepatitis B virus genotypes and variants

Chih-Lin Lin  1 , Jia-Horng Kao  2
Affiliations
Review

Hepatitis B virus genotypes and variants

Chih-Lin Lin et al. Cold Spring Harb Perspect Med. .

Abstract

At least 10 hepatitis B virus (HBV) genotypes (A to J) with distinct geographic distributions and several HBV mutants, including precore/core promoter mutations and pre-S/S deletion mutations, have been recognized to be not only predictive of liver disease progression but also associated with response to antiviral therapy. HBV genotype-specific pathogenesis may contribute to heterogeneous clinical outcomes in chronic hepatitis B patients across the world. For example, patients with HBV genotypes C and D infection have a lower rate of spontaneous HBeAg seroconversion. In addition, HBV genotypes C and D have a higher frequency of core promoter and pre-S mutations than genotypes A and B. Genotypes C and D also carry a higher lifetime risk of cirrhosis and HCC development than genotypes A and B. Core promoter and pre-S mutations also correlate with an increased risk of hepatocellular carcinoma (HCC). Therapeutically, genotypes A and B patients have a better response to interferon-based therapy than genotypes C and D patients, but the response to nucleos(t)ide analogs is comparable across different HBV genotypes. In conclusion, HBV genotypes and variants may serve as viral genetic markers to predict disease progression as well as help practicing physicians optimize individualized antiviral therapy in clinical practice.

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Figures

Figure 1.
Figure 1.
The partially double-stranded circular DNA of hepatitis B virus encodes four overlapping open reading frames: S for the surface or envelope gene; C for the core gene; P for the polymerase gene; and X for the X gene. Naturally occurring mutant strains including mutations in precore, core promoter, and deletion mutation in pre-S genes have been reported to be associated with the pathogenesis of progressive liver disease and risk of hepatocellular carcinoma (HCC) development. (From Kao et al. 2010; adapted, with permission, Elsevier © 2010.)
Figure 2.
Figure 2.
Odds ratios of hepatocellular carcinoma for HBV carriers by mutations in core promoter and pre-S regions in a meta-analysis. (Imaged created from data in Liu et al. 2009b.)
Figure 3.
Figure 3.
Hypothetical algorithm for HBV genotype–specific antiviral treatment in patients with chronic hepatitis B.
See this image and copyright information in PMC

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