Nucleotide change of codon 182 in the surface gene of hepatitis B virus genotype C leading to truncated surface protein is associated with progression of liver diseases

Abstract

Background & Aims: Hepatitis B virus (HBV) genotype C infection is associated with progression of hepatocellular carcinoma (HCC). Specific mutations of the HBV surface (S) gene have been reported to contribute to the development of HCC. In this study, novel nucleotide changes (sW182*) that result in a premature stop at codon 182 in the S gene of genotype C are investigated with regards to the development of HCC. Methods: A multi-probe real time PCR that enables rapid and reliable detection of sW182* was developed and applied to 292 DNA samples from Korean patients with diverse chronic liver diseases. Results: sW182* was detected in a total of 73 patients out of the 275 with positive amplification (26.5%). Its prevalence was significantly higher in patients with progressive forms of the disease (HCC and liver cirrhosis) than in patients with less severe forms of the disease (chronic hepatitis and carrier) [31.8% (56/176 patients) vs. 17.2% (17/99 patients); p = 0.010]. In addition, an in vitro study using cell lines stable expressing the S protein with sW182* also strongly supported its relationship with HCC. Conclusions: In the present study, we demonstrate that the sW182* of HBV could provide an important contribution to the progression of liver diseases, through molecular epidemiologic and in vitro studies. (C) 2011 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved.