The association of hepatitis B virus precore/basic core promoter mutations with genotype and progression of liver disease

Objective To study association of hepatitis B virus(HBV) precore (pre c)/basic core promoter(BCP) mutations with the genotype or the progression of liver disease. Methods The serum samples from 148 patients with HBV-relative diseases were collected, including 31 asymptomatic carriers, 32 with chronic hepatitis B (CHB), 40 with liver cirrhosis(LC) and 45 with hepatocellular carcinoma(HCC). The genes covering HBV pre c and BCP were amplified by nested polymerase chain reaction (nPCR). The PCR products were subjected to direct sequencing and the mutations in pre c 1896 and BCP 1762/1764 were determined by sequence analysis. HBV genotypes were also detected in the sera by restriction fragment length polymorphism based on S-gene PCR products. Results Of 148 serum samples of HBV, 128 were successfully genotyped and sequenced. There were 60 genotype B and 68 genotype C. The mutation in pre c (A1896) was significantly higher in genotype B than in genotype C (48.3% vs 29.34%, P0.05). On the contrary, the mutation at BCP (T1762/A1764) was significantly lower in genotype B than in genotype C (30.0% vs 73.5%, P0.01). The detection rate of pre c mutation (A1896) was almost same among CHB, LC and HCC. However, there was significant difference in the detection rate of BCP mutation (T1762/A1764) among patients with HCC, LC and CHB. Conclusions The mutations in the BCP region at nucleotide 1762/1764, which is common in genotype C, are closely related to progression of chronic liver disease. Mutation in the pre c (1896), which is frequent in genotype B, may contribute to inactivation of chronic liver disease.