Pre-S Deletion and Complex Mutations of Hepatitis B Virus Related to Young Age Hepatocellular Carcinoma in Qidong, China

Abstract

Background/AimTo investigate the roles of biomedical factors, hepatitis B virus (HBV) DNA levels, genotypes, and specific viral mutation patterns on the progression of hepatocellular carcinoma (HCC) patients below 40 years of age in Qidong, China.MethodsWe conducted a case-control study within a cohort of 2387 male HBV carriers who were recruited from August, 1996. The HBV DNA sequence was determined in 49 HCC and 90 chronic hepatitis (CH) patients below 40 years of age. Mutation exchanges during follow-up in 32 cases were compared with 65 controls with paired serum samples. In addition, a consecutive series of samples from 14 HCC cases were employed to compare the sequences before and after the occurrence of HCC.ResultsAfter adjustment for age, history of cigarette smoking and alcohol consumption, HBeAg positive, HBV DNA levels ≥4.00 log10 copies/mL, pre-S deletion, T1762/A1764 double mutations, and T1766 and/or A1768 mutations were associated with risk of young age HCC. Moreover, the presence of an increasing number of HCC-related mutations (pre-S deletion, T1762/A1764, and T1766 and/or A1768 mutations) was associated with an increased risk of young age HCC. Paired samples analysis indicated that the increased HCC risk for at-risk sequence mutations were attributable to the persistence of these mutations, but not a single time point mutation. The longitudinal observation demonstrated a gradual combination of pre-S deletion, T1762/A1764 double mutations, and T1766 and/or A1768 mutations during the development of HCC.ConclusionHigh HBV DNA levels and pre-S deletion were independent risk factors of young age HCC. Combination of pre-S deletion and core promoter mutations increased the risk and persistence of at-risk sequence mutations is critical for HCC development.

Evolutionary Changes of Hepatitis B Virus Pre-S Mutations Prior to Development of Hepatocellular Carcinoma

“…To our best knowledge, up to now, there are only limited longitudinal studies of pre-S mutations in relation to the development of HCC. Qu et al [ 25 ] showed that complex HBV mutations (pre-S deletions, T1762/A1764, and T1766 and/or A1768 mutants) were gradually combined during the development of HCC. Our previous study [ 12 ] also reported the emergence of de novo pre-S deletions before the development of HCC.…”

Effect of combined mutations in the enhancer II and basal core promoter of hepatitis B virus on development of hepatocellular carcinoma in Qidong, China

“…THE ANALYSIS USED data and stored samples from a prospective cohort in Qidong, Jiangsu Province, China . From 1 August to 30 September 1996, a total of 18 000 males aged 20–65 years, who were living in 17 townships of Qidong, were invited to participate in this HCC screening study.…”

Molecular Characterization of HBV Strains Circulating among the Treatment-Naive HIV/HBV Co-Infected Patients of Eastern India

“…For example, the classical A1762T/G1764A double mutation within the basal core promoter (nt 1742–1849 from EcoR I site) and the G1896A mutation in the precore (PC) (nt 1814–1900 from EcoR I site) region are often reported to be associated with advanced liver diseases including liver cirrhosis and HCC in HBV mono-infection [8], [9], [10], [11]. Similarly, the presence of Pre-S1/S2 deletion have also been reported to be associated with progressive liver disease [12] and increased risk for HCC [13] in HBV mono-infection. Moreover, the frequency of PreS2 deletion was previously found to be higher among the HIV/HBV co-infected population [14].…”