Authors: Yeh, C.-T.; Tang, J.-H.; Hsu, C.-W.; Chen, Y.-C.; Chang, M.-L.; Lin, C.-Y.

Source: Journal of Viral Hepatitis, Volume 15, Number 11, November 2008 , pp. 839-848(10)

Publisher: Wiley-Blackwell

Abstract:

Summary. 

The aim of this case control study was to investigate the clinical significance of hepatitis B virus nuclear core antigen (HBcAg) in young cirrhotic patients. Fifteen cirrhotic patients with nuclear HBcAg in the liver biopsies were included. Their clinicopathological parameters as well as the core gene sequences were compared with those of a sex- and age-matched (1 to 2) control group. The mean follow-up periods were 124 ± 80 and 102 ± 43 months, respectively. Expression of nuclear HBcAg in cirrhotic liver was significantly associated with higher aspartate aminotransferase levels (P = 0.001), alanine aminotransferase levels (P < 0.001), and alpha-fetoprotein levels (P = 0.002), as well as a shorter duration to develop hepatocellular carcinoma or liver decompensation (Kaplan-Meier method, P = 0.044). Sequence analysis revealed mutations on the nuclear localization signal (NLS) of core protein in five cirrhotic patients with nuclear HBcAg (Q171K in four and Q179K in one patients). Site-directed mutagenesis experiments demonstrated that both the Q171K and Q179K mutation enhanced nuclear localization of the core protein. In conclusion, expression of nuclear HBcAg in young cirrhotic patients was associated with more severe hepatitis activities as well as an unfavourable long-term outcome. Mutations on the NLS of core protein were selected in some patients with nuclear HBcAg.

Keywords: core antigen; hepatitis B; hepatocellular carcinoma; nuclear localization signal; viral mutant

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2893.2008.01017.x

Affiliations: 1: Department of Gastroenterology, Liver Cancer Research Centre, Chang Gung Memorial Hospital, Taipei, Taiwan

Publication date: 2008-11-01

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