HBV A(1762)T, G(1764)A mutations constitute a valuable biomarker to identify a subset of male HBsAg carriers aged >30 yr at extremely high risk of HCC in Guangxi, and likely elsewhere.

A matched nested case–control study of 33 paired cases and controls was conducted, based on a study cohort in Long An county, Guangxi, China, to determine whether infection with hepatitis B virus (HBV) with pre-S deletions is independently associated with the development of hepatocellular carcinoma (HCC), without the confounding effects of basal core promoter (BCP) double mutations. The prevalence of pre-S deletions was significantly higher in HCC (45.5 %, 15 of 33) than the controls (18.2 %, 6 of 33) (P<0.01), under the control of the influence of BCP double mutations. Most of the pre-S deletions occurred in, or involved, the 5′ half of the pre-S2 region and the difference between HCC (93.3 %, 14 of 15) and controls (66.7 %, four of six) was significant for this region (P=0.015). There was no significant difference in pre-S deletions between the BCP mutant group and BCP wild-type group (P>0.05), nor was the prevalence of pre-S deletions significantly different between genotypes B and C (P>0.1). These results suggest that pre-S deletions constitute an independent risk factor for HCC and their emergence and effect are independent of BCP mutations. The 5′ terminus of pre-S2 is the favoured site for the deletion mutations, especially in HCC cases. Further prospective studies are required to confirm the role of these mutations in the development of HCC.

Background/AimsAlthough there have been a few reports regarding the effect of basal core promoter (BCP) double mutations (A1762T and G1764A) on hepatitis B viral loads, the association remains uncertain. We aim to determine the association after controlling for HBeAg – a strong confounding factor.MethodsWe selected randomly 190 individuals from a Chinese cohort of 2258 subjects for cross-sectional analysis and 56 of the 190 for longitudinal analysis of viral loads.ResultsIn multivariable analysis of the cross-sectional data, BCP double mutations are significantly associated with lower viral loads in HBeAg positive subjects but no difference was found in anti-HBe positive subjects. Triple mutations at nucleotide (nt) 1753, 1762 and 1764 and mutations between nt 1809 and 1817, precore stop mutation (nt 1896) and genotype are not associated with viral loads in either HBeAg or anti-HBe positive subjects. Analysis of the longitudinal data yielded similar results to the cross-sectional data. Viral loads differ significantly between individuals infected with wild-type and BCP double mutations prior to HBeAg seroconversion but this difference is lost after seroconversion.ConclusionsBCP double mutations are associated with lower viral loads in HBeAg positive individuals but have no effect on the viral loads of anti-HBe positive individuals.

Recently, a complex (X/C) hepatitis B virus (HBV) recombinant, first reported in 2000, was proposed as a new genotype; although this was refuted immediately because the strains differ by less than 8 % in nucleotide distance from genotype C. Over 13.5 % (38/281) of HBV isolates from the Long An cohort in China were not assigned to a specific genotype, using current genotyping tools to analyse surface ORF sequences, and these have about 98 % similarity to the X/C recombinants. To determine whether this close identity extends to the full-length sequences and to investigate the evolutionary history of the Long An X/C recombinants, 17 complete genome sequences were determined. They are highly similar (96–99 %) to the Vietnamese strains and, although some reach or exceed 8 % nucleotide sequence difference from all known genotypes, they cluster together in the same clade, separating in a phylogenetic tree from the genotype C branch. Analysis of recombination reveals that all but one of the Long An isolates resembles the Vietnamese isolates in that they result from apparent recombination between genotype C and a parent of unknown genotype (X), which shows similarity in part to genotype G. The exception, isolate QL523, has a greater proportion of genotype C parent. Phylogeographic analysis reveals that these recombinants probably arose in southern China and spread later to Vietnam and Laos.

The Chinese national goals for control of hepatitis B virus (HBV) infection were to achieve a prevalence of HBsAg below 7% for the entire population, and 1% for children under 5-year old, by 2010. To determine whether Guangxi, a multi-minority province with a low socio-economic status and a very high prevalence of HBV, achieved this goal, a seroepidemiological survey of HBV infection was carried out using stratified, random cluster sampling. The results show that the overall prevalence of HBsAg is 9.16% [95% confidence interval (CI) = 8.32-10%]. The prevalence in males (10.96%, 95% CI = 9.64-12.28%) is significantly higher than in females (7.71%, 95% CI = 6.64-8.78%; χ(2) = 10.5923, P < 0.05). The prevalence in children under 5-year old is 3.62% (95% CI = 0.60-6.64%) and increases with age. The prevalence of HBsAg in non-immunized individuals is significantly higher than in those immunized completely, although not within 24 hr of birth (χ(2) = 31.426, P < 0.05); a significant difference was found in those below the age of 20 years but not in older persons. Gender, age, immunization history, and familial HBsAg carriers are risk factors for infection. In conclusion, this study indicates that Guangxi has not reached the goal for the control of HBV infection. Catch-up HBV immunization may not protect adults effectively against infection in highly endemic regions.