HDV infection rates in northern Vietnam

Abstract

Hepatitis D caused by the hepatitis delta virus (HDV) is a serious health problem in many regions of the world. A total of 546 HBV-infected patients were enrolled from 2013 to 2015 and classified clinically into the subgroups of chronic hepatitis B (CHB, n = 191), liver cirrhosis (LC, n = 147) and hepatocellular carcinoma (HCC, n = 208). The patients were screened for HDV-RNA by nested PCR assays. HDV genotypes were assessed by direct sequencing, followed by phylogenetic analysis. HDV-RNA was identified in 13% (71/546) of HBV-infected patients. The highest HDV prevalence was found in the LC group (19.7%), followed by the HCC (12%) and CHB (8.9%) groups (P = 0.017). HDV/HBV coinfections were significantly associated with a rather unfavourable clinical outcome, in particular with LC development compared to HBV monoinfection. Phylogenetic analyses indicated that the genotype HDV1 was, with a prevalence of 91%, by far the most common genotype in Vietnam, followed by HDV2 with 9%. Other HDV genotypes were not observed. In accordance with previous data obtained a decade ago, our results confirm a continuing high prevalence of HDV infection in hepatitis B patients in northern Vietnam with the HDV1 genotype still being the predominant genotype. HDV nucleic acid testing to minimize the associated risk should be considered.

Figure 1

Association of HDV infection with subclinical parameters. Bilirubin levels (A) and Platelet counts (B) in HBV infected patients with HDV and without HDV coinfection. Other parameters (liver enzymes: AST and ALT, HBV DNA loads, albumin, prothrombin, AFP) that did not reach the statistical significance were not presented in the figure. Box-plots illustrate medians with 25 and 75 percentiles with whiskers to 10 and 90 percentiles. P values were calculated by Mann-Whitney-Wilcoxon test.

Figure 2

Phylogenetic analysis of isolated HDV genotypes. (A) A phylogenetic tree was constructed based on the alignment of 235 bp of 57 nucleotide sequences isolated from HDV/HBV co-infected patients. 39 full-length HDV genomes through HDV1-8 retrieved from NCBI database along with GenBank accession numbers were included for the analysis. A neighbor-joining tree was constructed with a bootstrap of 1000 replicates. The bar at the base of the tree indicates the scale for nucleotide substitutions per position. (B) The phylogenetic tree was constructed only for HDV genotype 1 and 2 sequences and involves 82 nucleotide sequences (25 references of full-length HDV genome retrieved from NCBI database, 52 strains of HDV genotype 1 (denoted as ♦) and 5 HDV genotype 2 (denoted as •) from HBV/HDV coinfected patients in our study group.