Association of hepatitis B virus pre-S deletions with the risk of development of hepatocellular carcinoma

Abstract

Background and Aims: Recent studies suggest that hepatitis B virus (HBV) pre-S/S mutations are associated with hepatocellular carcinoma (HCC) development [1, 2]. However, in these case-control studies, patients were not matched for age, gender and hepatitis B e-antigen (HBeAg) status. We aimed to investigate the association between pre-S deletions and HCC using 1) a matched case-control approach and 2) a longitudinal approach. In addition, the association between pre-S deletions and HBeAg seroconversion was investigated. Methods: HBV pre-S deletions were determined by DNA sequencing in sera collected from 117 HCC and 117 non-HCC chronic hepatitis B (CHB) patients matched with age, gender and HBeAg status, as well as in sera collected before the development of HCC. HBV pre-S deletions were also determined in 76 non-HCC CHB patients before and after HBeAg seroconversion. Results: Pre-S deletions were detected in 33 out of 117 HCC cases (28.2%). At the time of writing, nucleotide sequence analysis in 78 HCC/non-HCC-matched pairs showed that 26 HCC (33.3%) and 15 nonHCC (19.2%) patients acquired pre-S deletions (P = 0.045). In the longitudinal study, serum samples collected 1−7 years before HCC development were assessed in 16 HCC cases with pre-S deletions. Pre-S deletions were absent in 4 cases before HCC development (25.0%). Pre-S deletions were also assessed in serum samples collected from 76 non-HCC CHB patients 1.4−8.3 months (median 5.6 months) before HBeAg seroconversion and 1.7−7.6 months (median 5.6 months) after seroconversion. Seven patients had newly emerged pre-S deletions after HBeAg seroconversion (9.2%) while 5 had pre-S deletions before HBeAg seroconversion (6.6%). Conclusions: These findings suggested that pre-S deletions were associated with HCC development. 25% of HCC patients had developed pre-S deletions within 1 year before the occurrence of HCC. However its association with HBeAg seroconversion was not clear. These results are being validated by our on-going studies with a larger number of patients. References [1] Choi M.S., Kim D.Y., Lee D.H., et al. (2007) J Viral Hepat. 14:161−8. [2] Lin C.L., Liu C.H., Chen W., et al. (2007) J Gastroenterol Hepatol. 22:1098– 103.