Comparison of the Characteristics of Hepatitis B Virus Whole Genomes Derived From Patients With Hepatocellular Carcinoma and Chronic Hepatitis B Infection

Abstract Background: Hepatocellular carcinoma (HCC) caused by hepatitis B virus (HBV) infection is a serious public health problem in China. The aims of the present study was to report HCC prevalence in China and characterize the whole gene sequences of HBV derived from patients diagnosed with HCC as well as those with chronic hepatitis B (CHB) infections.Methods: Patients in the HCC group and the CHB group were recruited from national HBV surveillance sites, which were matched by age, gender, and region. All serum samples were tested for serological markers. Polymerase chain reaction (PCR) was used to amplify the HBV complete genome sequences. Then the analysis of the full-length HBV genomes was performed with bioinformatics and statistical software.Results: Serum samples were collected from 51 patients with HBV-related HCC and 76 patients with CHB. All patients were from six provinces (Guangxi, Hebei, Henan, Hunan, Qinghai, and Shanghai) in China. Sequencing and analysis of the full-length HBV genomes revealed the presence of four genotypes (B, C, CD, and I). The distribution of HBV genotypes and the positivity rate of the hepatitis B e antigen differed between the two groups. A total of 148 substitution sites deemed statistically significant were identified between the HCC and CHB groups. In addition, three mutational sites associated with HCC, (F22I/L/P in the pre-S2 region, P33S/T and S144A/T/V in the X region) were identified. Deletions to the pre-S and X regions were found in both HCC and CHB patients. However, deletions to the X region were more common in the HCC group than the CHB group.Conclusions: In this study the hotspot mutations associated with high risk of HCC mostly occurred in the sequences and some substitutions (C1470A/T, T1803A/G, and C1804T) that have not been previously reported. It was implicated that aa33 and aa144 substitution in X region may be new predictive markers for HCC. The results of our study would provide important basic information for HCC prevention.