Hepatitis B virus-DNA level and basal core promoter A1762T/G1764A mutation in liver tissue independently predict postoperative survival in hepatocellular carcinoma

Abstract

Hepatitis B virus (HBV) is a major etiological factor of hepatocellular carcinoma (HCC). However, the postoperative prognostic value of the virological factors assayed directly from liver tissue has never been investigated. To address this issue, 185 liver samples obtained from the noncancerous part of surgically removed HBV‐associated HCC tissues were subjected to virological analysis. Assayed factors included the amount of HBV‐DNA in the liver tissues; genotype; and the presence of the HBV precore stop codon G1896A mutation, basal core promoter A1762T/G1764A mutation, and pre‐S deletions/stop codon mutation. All virological factors and clinicopathological factors were subjected to Cox proportional hazard model analysis to estimate postoperative survival. It was found that an HBV‐DNA level >3.0 × 10⁷ copies/g of liver tissue and the presence of the basal core promoter mutation independently predicted disease‐free (adjusted hazard ratio 1.641 [95% confidence interval (CI) 1.010‐2.667] and 2.075 [95% CI 1.203‐3.579], respectively) and overall (adjusted hazard ratio 2.807 [95% CI 1.000‐7.880] and 5.697 [95% CI 1.678‐19.342], respectively) survival. Kaplan‐Meier survival analysis indicated that in‐frame, short stretch (100 bp) pre‐S deletions, were significantly associated with poorer disease‐free (P = 0.005) and overall (P = 0.020) survival. A hot deletion region located between codons 107 and 141 of the pre‐S sequence was identified for the short stretch pre‐S deletion mutants. Conclusion: The amount of HBV‐DNA in liver tissue and the presence of the basal core promoter mutation were two independent predictors for postoperative survival in HCC. A short stretch pre‐S deletion located between codons 107 and 141 was strongly associated with a poorer postoperative prognosis. (Hepatology 2010)