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Different hepatitis B virus core gene mutations in children with chronic infection and hepatocellular carcinoma

Department of Paediatrics, Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan

Correspondence to:
Correspondence to:
Dr M-H Chang, Department of Paediatrics, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan 100; mhchang{at}ha.mc.ntu.edu.tw

Background: The significance of mutations of hepatitis B virus (HBV) precore/core antigen in causing persistent infection and subsequent liver diseases is debatable.

Aim: To investigate HBV core gene sequence changes in children with chronic HBV infection and their implications in hepatocellular carcinoma (HCC).

Methods: Thirty one chronic HBV infected children with documented hepatitis B e antigen seroconversion selected from 415 long term carrier children and 12 HBV related HCC children were studied. Four serial serum samples before and after hepatitis B e antigen seroconversion from each of the 31 children, and one serum sample taken from the 12 HCC children were subjected to HBV core gene sequence analysis.

Results: Mutations accumulated as chronic infection persisted and most frequently occurred at core gene codon 21 (29%), codon 147 (29%), codon 65 (16%), and precore stop codon 28 (74%) in the 31 chronic HBV infected children. Core gene mutation sites in HCC children were identified at core codons 74, 87, and 159. HCC children had more mutations in the core gene than those with chronic HBV infection (p=0.013).

Conclusion: Accumulation of mutations of HBV core region in HCC children differ from those in chronic HBV infected children. This may be a clue to the pathogenesis of paediatric HCC.

Keywords: hepatitis B virus; hepatocellular carcinoma; hepatitis B e antigen; hepatitis B core antigen

Abbreviations: HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; HBcAg, hepatitis B core antigen; CTL, cytotoxic T lymphocytes; PCR, polymerase chain reaction; ALT, alanine aminotransferase