ABSTRACT
Hepatitis delta virus (HDV) is a subviral pathogen of humans, a satellite of hepatitis B virus (HBV) that induces severe acute and chronic liver diseases. The genus Deltavirus consists of eight clades or genotypes, with HDV1 being ubiquitous and frequently characterized. In Turkey, HDV1 infection is highly endemic among HBsAg carriers, especially in the southeastern region. In this study, we analyzed 34 samples from patients who were chronically infected with HBV/HDV, originating from 22 cities of rural regions in the central and eastern parts of Turkey, in order to determine the levels of viral replication and genetic diversity. HDV RNA levels ranged between 3.02 and 8.75 Log copies/mL, and HBV DNA was detected in 25 samples (73.5%), with values ranging from 2.53 to 5.30 Log copies/mL. Analysis of nucleotides 900-1280 of HDV genomes (n = 34) and full-length (n = 17) sequences indicated that all of the strains belonged to genotype HDV1. However, a high genetic diversity was observed among the isolates, with a mean full-length dissimilarity score of 13.05%. HDV sequences clustered with sequences from Western Europe (n = 11), Eastern Europe and Asia (n = 19) or Africa (n = 4). HDV1 isolates related to strains of African origin had a serine residue instead of an alanine at position 202 of the large delta protein. HBV preS1 sequences obtained for 34 isolates indicated an HBV/D genotype in all cases. Taken together, our results indicate that in Turkey, where HBV-HDV dual infection is highly endemic, both viruses have high levels of replication, and HDV strains exhibit wide genetic diversity, which might reflect ancient evolution and/or successive outbreaks.
Subject(s)
Genetic Variation , Hepatitis D, Chronic/epidemiology , Hepatitis D, Chronic/virology , Hepatitis Delta Virus/classification , Hepatitis Delta Virus/isolation & purification , Adult , Aged , Cluster Analysis , Endemic Diseases , Female , Genotype , Hepatitis B, Chronic/complications , Hepatitis Delta Virus/genetics , Humans , Male , Middle Aged , Molecular Epidemiology , Molecular Sequence Data , Phylogeny , RNA, Viral/genetics , RNA, Viral/isolation & purification , Rural Population , Sequence Analysis, DNA , Turkey/epidemiology , Viral LoadABSTRACT
The aim of this study was to examine the genetic variability of the hepatitis B virus (HBV) and its significance. HBV genotypes, core promoter and precore mutants were characterized in 109 consecutive patients with biopsy-proven HBV chronic hepatitis. Genotypes A (26.6%), B (12.8%), C (18.3%), D (18.3%), and E (14.7%) indicate a wide genotypic distribution. Patients were from Asia (30.3%), Europe (28.4%), Sub Saharan Africa (23.9%), the Caribbean (10.1%), North Africa (5.5%), and Madagascar (1.8%). HBV genotypes A and D (HBV/A and /D) infected all subgroups except Asian patients. HBV/B or /C were found in 97% of Asian patients, whereas HBV/E only infected sub-Saharan African and Caribbean patients. Differences according to genotypes were: an increased prevalence of anti-HBe antibodies in patients infected with HBV/D (P = 0.003), higher serum transaminases in patients infected with HBV/A and/D (P = 0.043), more severe liver fibrosis in patients infected with HBV/A, /C and/D (P = 0.02). Precore and core promoter mutants were found in 87% of anti-HBe positive patients, and were associated with HBV/D (P = 0.04) and severe liver fibrosis (P = 0.002). It is concluded that HBV genotypes A, B, C, D, and E circulate in the Seine Saint Denis District, reflecting the geographical origin of patients. HBV/A, /C and/D seem to be associated with more severe hepatic disease.
