Study Of HBV-X Gene Mutation Among Patients With HBV-related Chronic Hepatitis, Liver Cirrhosis And Primary Liver Cancer

Background: Hepatitis B virus X gene(HBV-X gene) plays importantroles in the process that chronic hepatitis B(CHB) grows into livercirrhosis(LC) and then primary liver cancer(PLC).HBV-X gene sequenceoften has deletion and mutation during the integration into the host genome,consequently,has influence on the HBV replication and strongly links tohepatocarcinogenesis.Objective:To study the relationship between hepatocarcinogenesis andthe mutation in X gene among patients with chronic hepatitis B virus(HBV)infection,such as CHB,LC and PLC.Methods:The serum samples from89patients with chronic HBVinfection who visited the Second Affiliated Hospital of Chongqing MedicalUniversity from2011to2013were collected.Polymerase chain reaction(PCR) was used to amplify the X gene of HBV-DNA extracted from theserum samples,after sequencing,the HBV-X genome was compared withthose reported in GenBank to find the variable sites and variantforms.Chi-square and one-way ANOVA were used for the statistical analysisafterwards,whereas genotypes were determined by the genotyping tool ofthe National Center for Biotechnology Information.Results:All patients were genotype B or C.Among HBeAg-positivepatients,46.2%were genotype B,and53.8%were genotype C;among HBeAg-negative patients,81.2%were genotype B,and18.8%were genotypeC(P=0.001).PLC patients had a significantly higher risk of mutation in thebasic core promoter(BCP) region than the CHB and LC group(69.2%vs34.4%and61.3%,P<0.05);in addition,an evident T-base deficiency wasobserved at nt1821site（88.5%vs53.1%and71%,P=0.014）. Among CHBand LC patients,those with genotype C had a significantly higher risk ofBCP double mutation than those with genotype B （61.5%vs15.8%,P=0.007;83.3%vs47.4%,P=0.045）.The incidence of BCP doublemutation was significantly higher in the low-viral load group (≤10^6copies/ml) than in the high-viral load group (>10^6copies/ml)（81.3%vs47.9%,P=0.015）.Conclusions: The BCP double mutation and T-base deficiency atnt1821site may play important roles in the development of PLC.