Risk for hepatocellular carcinoma with respect to hepatitis B virus genotypes B/C, specific mutations of enhancer II/core promoter/precore regions and HBV DNA levels

Gut. 2008 Jan;57(1):98-102. doi: 10.1136/gut.2007.119859. Epub 2007 May 4.

Abstract

Background/aim: To examine the risks for hepatocellular carcinoma (HCC) with respect to hepatitis B virus (HBV) genotypes, specific viral mutations (MT), serum HBV DNA levels, and cirrhosis.

Methods: HBV genotypes, 1653/1753/core promoter (CP)/precore MT and HBV DNA levels were determined in 248 HBV patients with HCC and 248 HBV controls.

Results: Genotype C, CP-MT, T1653, HBV DNA levels >or=4 log(10) copies/ml and cirrhosis had a higher risk for HCC compared to patients with genotype B (p = 0.001, OR 1.9), CP wild-type (WT) (p<0.001, OR 4.1), C1653 (p = 0.028, OR 2.4), HBV DNA <4 log(10) copies/ml (p = 0.003, OR 2.1) and without cirrhosis (p<0.001, OR 4.0) respectively. Multivariate analysis showed that CP-MT, T1653, HBV DNA >or=4 log(10) copies/ml and cirrhosis were independent factors for HCC (all p<0.05). A receiver operating characteristics curve showed no cut-off HBV DNA level associated with minimal chance of HCC. Patients with CP-MT and cirrhosis had a 22.2-fold increased risk of HCC compared to patients with CP-WT and without cirrhosis. Patients with CP-MT and HBV DNA levels >or=4 log(10) copies/ml had a 7.2-fold increased risk of HCC compared to patients with CP-WT and HBV DNA levels <4 log(10) copies/ml. Patients with CP-MT and T1653 had a 9.9-fold increased risk of HCC compared to patients with wild-type for both regions.

Conclusions: CP-MT, T1653, HBV DNA levels >or=4 log(10) copies/ml and cirrhosis are independent factors for development of HCC. The risks increased substantially in patients having these factors in combination.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Hepatocellular / virology*
  • Case-Control Studies
  • DNA, Viral / blood
  • Enhancer Elements, Genetic / genetics*
  • Female
  • Genotype
  • Hepatitis B virus / genetics*
  • Humans
  • Liver Neoplasms / virology*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mutation / genetics*
  • Promoter Regions, Genetic / genetics*
  • ROC Curve

Substances

  • DNA, Viral