ABSTRACT
Hepatitis B virus (HBV) has been classified into 8 genotypes (A-H). Genotypes A, D and F have been identified in some South American countries, but in Venezuela studies have been more restricted to aboriginal communities where genotype F is predominant. The aim of the present study was to identify the prevalence of HBV genotypes among native HBsAg carriers in Venezuelan urban areas. In addition, we correlated the predominant HBV genotype with epidemiological, serological and virological features of the infection. Non-Venezuelan migrant patients were excluded from this study. Serum samples from 90 patients (21 children and 69 adults) with chronic hepatitis B (CHB) were analyzed. Seventy-four patients had CHB e-antigen positive and 16 CHB e-antigen negative. HBV DNA serum levels of the whole group ranged from 4.1 to 8.8 log10 IU/mL. Patients with CHB e-antigen positive showed significantly higher viral loads (P = 0.0001) than the group with CHB e-antigen negative. Eighty-eight patients (97.8%) exhibited HBV genotype F while two non-related patients (2.2%) were infected with A + F genotypes. Genotype F is the main circulating HBV strain among HBsAg carriers from Venezuelan urban areas. This genotype is associated mostly with CHB eantigen positive and high rate of transmission. Progression to cirrhosis and hepatocellular carcinoma could be major clinical events of this patient population independently of age at acquisition or transmission route.
Subject(s)
Hepatitis B virus/genetics , Hepatitis B, Chronic/diagnosis , Urban Population , Adolescent , Adult , Age Distribution , Biomarkers/blood , Child , Child, Preschool , DNA, Viral/blood , Female , Genotype , Hepatitis B Surface Antigens/blood , Hepatitis B e Antigens/blood , Hepatitis B virus/immunology , Hepatitis B, Chronic/epidemiology , Humans , Male , Middle Aged , Prevalence , Prognosis , Urban Population/statistics & numerical data , Venezuela/epidemiology , Viral LoadABSTRACT
AIMS: Autoimmune hepatitis (AIH) is a progressive liver disease characterized by the presence of circulating autoantibodies, hypergammaglobulinaemia and a favourable response to immunosuppressive treatment. Although the pathogenesis of type 1 AIH is unknown, disease susceptibility is partially determined by genes linked to the class II region of the major histocompatibility complex. Type 1 AIH has been associated with DRB1*03, DRB1*04 and DRB3 alleles in European and North American Caucasians, with DRB1*0405 in Japanese, with DRB1*0404 in Mexican, and with DRB1*1301 in Argentinean populations. METHODS: To analyse the molecular basis of these associations in Venezuela (mestizo population), we examined the frequency of human leucocyte antigens (HLA)-A -B -C, HLA-DQ and HLA-DR genes by low- and high-resolution oligonucleotide typing in a population of 41 type 1 AIH patients and 111 ethnic- and aged-matched healthy subjects. RESULTS: The frequencies of both DRB1(*)1301 (P<0.0001) and DRB1*0301 (P<0.005) were significantly higher in patients than in controls. In addition, patients showed a strong association with the DRB3 allele (P<0.01). In contrast, the DQB1*04 allele was significantly decreased in the patient group (P<0.01). The frequencies of haplotypes A*01-B*08-DQB1*02-DRB1*03-DRB3, DQB1*05-DRB1*1301, DQB1*06-DRB1*1301 and A*02-DRB1*1301, B*45-DRB3 were significantly increased in type 1 AIH patients compared with the controls (P<0.01). CONCLUSIONS: In conclusion, our data indicate that type 1 AIH predisposition in a Venezuelan mestizo population of different ethnic backgrounds is associated with DRB1*1301 and DRB1*0301 alleles. In addition, our findings suggest that protection against disease might be conferred by the DQB1*04 allele, with distinct ethnic differences from other populations.
