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J Hepatol. 2014 Aug;61(2):408-17. doi: 10.1016/j.jhep.2014.04.041. Epub 2014 May 5.

Hepatitis B virus PreS/S gene variants: pathobiology and clinical implications.

Author information

1
Division of Clinical and Molecular Hepatology, University Hospital of Messina, Via Consolare Valeria, 1, 98124 Messina, Italy; Department of Pediatric, Gynecologic, Microbiological and Biomedical Sciences, University Hospital of Messina, Via Consolare Valeria, 1, 98124 Messina, Italy. Electronic address: tpollicino@unime.it.
2
Division of Clinical and Molecular Hepatology, University Hospital of Messina, Via Consolare Valeria, 1, 98124 Messina, Italy; Department of Clinical and Experimental Medicine, University Hospital of Messina, Messina, Italy.
3
Division of Clinical and Molecular Hepatology, University Hospital of Messina, Via Consolare Valeria, 1, 98124 Messina, Italy; Department of Clinical and Experimental Medicine, University Hospital of Messina, Messina, Italy. Electronic address: raimondo@unime.it.

Abstract

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:

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

PMID:
24801416
DOI:
10.1016/j.jhep.2014.04.041
[Indexed for MEDLINE]
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