Association of hepatitis B virus Pre-S mutations with the risk of hepatocellular carcinoma development

Introduction: Recent studies suggest that hepatitis B virus (HBV) Pre-S/S mutations are associated with the development of hepatocellular carcinoma (HCC). However, in these case-control studies, the patients were not matched for age, gender and hepatitis B e-antigen (HBeAg) status. We aimed to investigate the association between PreS deletions and HCC using (1) a matched case-control approach and (2) a longitudinal approach. Methods: HBV PreS deletions were determined by DNA sequencing in sera collected from 105 HCC and 105 non-HCC patients matched with age, gender and HBeAg status, as well as in sera collected before the development of HCC. Results: PreS deletions were detected in 27 of 105 HCC cases (25.7%). At the time of writing, nucleotide sequence analysis in 68 HCC/non-HCC­–matched pairs showed that 20 HCC (29.4%) and 9 non-HCC (13.2%) patients acquired PreS2 deletions (P=0.035). In the longitudinal study, serum samples collected 1 to 7 years before HCC development were assessed in 12 HCC cases with PreS deletions. PreS deletions were absent in seven cases before HCC development (58.3%). Conclusion: The findings from this preliminary study suggested that PreS deletions, especially PreS2 deletions, were associated with HCC development. These results are being validated by our on-going studies with a larger number of patients