Elsevier

Journal of Hepatology

Volume 61, Issue 2, August 2014, Pages 408-417
Journal of Hepatology

Review
Hepatitis B virus PreS/S gene variants: Pathobiology and clinical implications

https://doi.org/10.1016/j.jhep.2014.04.041Get rights and content
Under a Creative Commons license
open access

Summary

The emergence and takeover of hepatitis B virus (HBV) variants carrying mutation(s) in the preS/S genomic region is a fairly frequent event that may occur spontaneously or may be the consequence of immunoprophylaxis or antiviral treatments. Selection of preS/S mutants may have relevant pathobiological and clinical implications. Both experimental data and studies in humans show that several specific mutations in the preS/S gene may induce an imbalance in the synthesis of the surface proteins and their consequent retention within the endoplasmic reticulum (ER) of the hepatocytes. The accumulation of mutated surface proteins may cause ER stress with the consequent induction of oxidative DNA damage and genomic instability. Viral mutants with antigenically modified surface antigen may be potentially infectious to immune-prophylaxed patients and may account for cases of occult HBV infection. In addition, preS/S variants were reported to be associated with cases of fulminant hepatitis as well as of fibrosing cholestatic hepatitis, and they are associated with cirrhosis and hepatocellular carcinoma development.

Keywords

HBV preS/S genetic variability
Vaccine escape variants
Occult HBV infection
Endoplasmic reticulum stress signaling pathway
Ground glass hepatocytes
Hepatocellular carcinoma

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