Distribution and Hepatocellular Carcinoma–Related Viral Properties of Hepatitis B Virus Genotypes in Mainland China: A Community-Based Study

Abstract

Introduction: Hepatitis B virus (HBV) genotypes, replication status, and mutations have been associated with the risk of hepatocellular carcinoma (HCC). Our aim was to study the distribution and HCC-related viral properties of HBV genotypes/subgenotypes in Mainland China.Methods: A multistage cluster probability sampling method was applied to select 81,775 participants between 1 and 59 years at 160 national disease surveillance points. We examined hepatitis B surface antigen, HBV genotypes and subgenotypes, hepatitis B e antigen, viral load, and mutations in the PreS and core promoter regions of HBV genome.Results: HBV subgenotypes B2 (27.3%), C1 (10.7%), and C2 (58.0%) were predominant. Genotype D (D1, 80.8%) was frequent in the Uygur. We identified a new subgenotype, C9, mainly in Tibetans. Compositions of subgenotypes B2 and C1 and genotype mixture increased from the North to Central South, which was consistently associated with the increasing prevalence of hepatitis B surface antigen. Hepatitis B e antigen positivity and viral loads were higher in the young with genotype B and declined more rapidly with increasing age than those with genotype C. In contrast to G1896A, PreS deletion, T31C, T1753V, and A1762T/ G1764A were more frequent in subgenotype C2 than in subgenotype B2. A1762T/G1764A, T1753V, C1653T, and G1896A, except PreS deletion, consecutively increased with increasing age.Conclusion: HBV subgenotypes B2, C1, and C2 are endemic in Mainland China. HBV genotype C exhibits less replication activity in the young and harbors higher frequencies of the HCC-associated mutations than genotype B.Impact: These basic data could help evaluate the association of HBV variations with HCC. Cancer Epidemiol

HLA-DPPolymorphisms Affect the Outcomes of Chronic Hepatitis B Virus Infections, Possibly through Interacting with Viral Mutations

“…Serum anti-HCV, anti-HIV, and ALT levels were examined in the hospitals where the study participants were recruited. Extraction and quantification of HBV DNA and HBV genotyping were carried out as previously described (20,33).…”

Hepatitis B Virus Combo Mutations Improve the Prediction and Active Prophylaxis of Hepatocellular Carcinoma: A Clinic-Based Cohort Study

“…HBV DNA was extracted from frozen sera, quantified twice using quantitative PCR, and genotyped as previously described (20). The core promoter region from nt.1626 to nt.2004 of HBV genome was amplified using nested PCR and directly sequenced or sequenced after cloning (25,31).…”

“…Some of these risk factors have been used to construct clinical scoring systems for the prediction of HCC (12)(13)(14)(15). However, HBeAg sero-status and the levels of HBV DNA and ALT are usually changeable during the long-term HBV infection, and differ among the patients infected with different HBV genotypes, which might result in low discriminatory performance in different populations (16)(17)(18)(19)(20)(21). Therefore, more robust biomarkers are needed to improve the prediction power of the current clinical scoring systems.…”

Cancer Evo-Dev, a novel hypothesis derived from studies on hepatitis B virus-induced carcinogenesis

“…Approximately 8.5% of acute hepatitis B in adults in Shanghai, China, develops into chronic HBV infection 6 months after acute infection [13] . In mainland China where genotypes B (B2) and C (C2 and C1) are endemic, HBV subgenotype B2 is more apt to causing acute infection because of higher viral load in the virus-providing chronic carriers whereas HBV subgenotype C2 is more apt to causing chronic transformation following an acute course [13,14] . HBV C2 is more likely to develop liver cirrhosis and HCC than does HBV B2, the two major HBV subgenotypes endemic in China, possibly because of the stickiness nature of HBV subgenotype C2 [15][16][17] .…”