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.
Highlights
Chronic hepatitis B virus (HBV) infection is a serious global health problem and an important cause of morbidity and mortality in endemic areas such as Africa, South-East Asia and China, where most infections are acquired at birth or during childhood
HBV genotypes B, C, D and C/D recombinant partitioned differently according to geographical regions and ethnic populations; no other genotypes were identified in this study
A large-scale survey on the geographical and ethnic distribution of the HBV C/ D recombinant in western China reinforce the results of our previous reports based on smaller samples [23]
Summary
Chronic hepatitis B virus (HBV) infection is a serious global health problem and an important cause of morbidity and mortality in endemic areas such as Africa, South-East Asia and China, where most infections are acquired at birth or during childhood. Eight HBV genotypes (A to H) have been identified according to a divergence of more than 8% in the entire nucleotide sequence, and two additional genotypes I and J were tentatively proposed more recently [1,2,3]. Subgenotypes have been described within these HBV genotypes based on a divergence in the complete nucleotide sequence greater than 4% and less than 8% [4]. Recombinant forms B2–B5 formed by recombination between HBV genotype B and C, are the predominant HBV genotype B strains that prevail in South-East Asia [5,6]. Recombination between genotype A and D was identified in Italy, South Africa and India [7,8,9]. Two studies comprehensively analyzed all available full-length HBV genomes in GenBank/EMBL/DDBJ and reported the frequent occurrence of recombination event between two or more HBV strains [14,15]
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