Geographical and Ethnic Distribution of the HBV C/D Recombinant on the Qinghai-Tibet Plateau

Abstract

Two forms of hepatitis B virus (HBV) C/D recombinant have been identified in western China, but little is known about their geographical and ethnic distributions, and particularly the clinical significance and specific mutations in the pre-core region. To address these questions, a total of 624 chronic HBV carriers from four ethnic populations representing five provinces in western China were enrolled in this study. Genotypes were firstly determined by restriction fragment length polymorphism, and then confirmed by full or partial genome nucleotide sequencing. The distribution of HBV genotypes was as follows: HBV/B: 40 (6.4%); HBV/C: 221 (35.4%); HBV/D: 39 (6.3%); HBV/CD: 324 (51.9%). In the 324 HBV C/D recombinant infections, 244 (75.3%) were infected with the “CD1” and 80 (24.7%) were infected with the “CD2.” The distribution of HBV genotypes exhibited distinct patterns in different regions and ethnic populations. Geographically, the C/D recombinant was the most prevalent HBV strain on the Qinghai-Tibet Plateau. Ethnically, the C/D recombinant had a higher prevalence in Tibetan patients than in other populations. Clinically, patients with HBV/CD1 showed significantly lower levels of serum total bilirubin than patients with HBV/C2. The prevalence of HBeAg was comparable between patients with HBV/CD1 and HBV/C2 (63.3% vs 50.0%, P = 0.118) whether patients were taken together or stratified by age into three groups (65.6% vs 58.8% in <30 years, P = 0.758; 61.9% vs 48.0% in 30–50 years, P = 0.244; 64.3% vs 33.3%, P = 0.336). Virologically HBV/CD1 had a significantly lower frequency of G1896A than HBV/C2. In conclusion, the HBV C/D recombinant is restricted to the Qinghai-Tibet Plateau in western China and is found predominantly in Tibetans. The predominance of the premature pre-core stop mutation G1896A in patients with the HBV C/D recombinant may account for the higher prevalence of HBeAg in these patients.

A novel B/C inter-genotype recombinant of hepatitis B virus identified in north-west China

“…The characteristics of life-long persistent infection and the prevalence of different genotypes in the same region offer a high probability of co-infection of different genotypes in one host and thus a high risk for virus recombination. In north-west China, HBV inter-genotype recombinants have been reported frequently over the last decade (Wang et al, 2005;Zhou et al, 2011). The present study reports a novel recombinant HBV between genotypes B and C in an asymptomatic carrier from Lanzhou, a major city in Gansu Province in north-west China.…”

Hepatitis B Virus Genotypes and Variants

“…For example, HBV genotype B2 is a recombinant, in which the majority of the genetic framework is HBV genotype B, and the precore/core region is from genotype C (Sugauchi et al 2002). HBV genotypes C/D recombinant is dominant in the Qinghai-Tibet plateau in Southwest China (Wang et al 2005;Zhou et al 2011;Shen et al 2014). HBV genotype I, a novel intergenotypic recombination among genotypes A, C, and G was isolated in Vietnam and Laos (Tran et al 2008;Phung et al 2010).…”

Molecular identification of hepatitis B virus genotypes/subgenotypes: Revised classification hurdles and updated resolutions

“…Although more than 60% of recombinant isolates have their breakpoint between nucleotides that span 1640-1900 (which encompasses the core region), recombinant strains with breakpoints in the S gene (350-500, 3150-100 or 650-830) have also been identified [134] . Markedly, the largest breakpoints have been detected among HBV isolates from Tibet, in which two different genotypes of C and D (subgeno-types C1 or C2 with D1 or D2) formed 50% of the recombination [135,136] .…”