Study of HBV- X gene mutation among patients with HBV- related chronic hepatitis, liver cirrhosis, and primary liver cancer

Objective To study the relationship between hepatocarcinogenesis and the mutation in X gene among patients with chronic hepatitis B virus ( HBV) infection, such as chronic hepatitis B ( CHB) , liver cirrhosis ( LC) and primary liver cancer ( PLC) . Methods The serum samples from 89 patients with chronic HBV infection who visited the Second Affiliated Hospital of Chongqing Medical University from2011 to 2013 were collected. PCR was used to amplify the X gene of HBV DNA extracted from the serum samples. After sequencing, the HBV- X genome was compared with those reported in GenBank to find the variable sites and variant forms. Chi- square and one- way ANOVA were used for the statistical analysis afterwards, whereas genotypes were determined by the genotyping tool of the National Center for Biotechnology Information. Results All patients were genotype B or C. Among HBeAg- positive patients, 46. 2% were genotype B, and53. 8% were genotype C; among HBeAg- negative patients, 81. 2% were genotype B, and 18. 8% were genotype C ( P = 0. 001) . PLC patients had a significantly higher risk of mutation in the basic core promoter ( BCP) region than the CHB and LC groups ( 69. 2% vs 34. 4%and 61. 3%, P < 0. 05) ; in addition, an evident T- base deficiency was observed at nt1821 site ( 88. 5% vs 53. 1% and 71%, P =0. 014) . Among CHB and LC patients, those with genotype C had a significantly higher risk of BCP double mutation than those with genotype B ( 61. 5% vs 15. 8%, P = 0. 007; 83. 3% vs 47. 4%, P = 0. 045) . The incidence of BCP double mutation was significantly higher in the low- viral load group ( ≤106copies /ml) than in the high- viral load group ( > 106copies /ml) ( 81. 3% vs 47. 9%, P = 0. 015) .Conclusion The BCP double mutation and T- base deficiency at nt1821 site may play important roles in the development of PLC.