RESUMO
Hepatitis B virus (HBV) genotypes are important in both the clinical manifestation of disease and treatment response. Although Kenya belongs to the African Region (AFR-E) characterized by high mortality and hyperendemicity of HBV, there is a paucity of HBV genotyping data. The aim of this study was to molecularly characterize the basic core promoter/precore (BCP/PC) and complete surface (S) regions of HBV isolated from 61 HBsAg-positive liver disease patients attending Kenyatta National Hospital in Nairobi. HBsAg, HBeAg and viral loads were determined. HBV DNA was amplified and sequenced from 58/61 patients. In addition to the complete genome of two isolates, the BCP/PC and the complete S regions of 43 and 38 isolates, respectively were sequenced. Following phylogenetic analysis of the S region, 38 isolates clustered with subgenotype A1, whereas two isolates clustered with genotype D, one with subgenotype D1 and another as an outlier of the clade containing subgenotype D6 and the D/E recombinant. When the complete genome of the latter isolate was sequenced it clustered with D6. The majority of isolates belonged to serological subtype adw2 and only four to ayw2. Three distinct groups of subgenotype A1, distinguished by different amino acid motifs, circulate in Kenya: two in the African cluster and a monophyletic clade in the "Asian" cluster. HBeAg-negativity was a result of G1896A in genotype D isolates, whereas in subgenotype A1, the HBeAg-negativity was a result of mutations in the Kozak region (1809-1812) or precore start codon (1814-1816). Mutations at positions 1762 and 1764 occurred more frequently in HCC patients (p<0.05). In conclusion, subgenotypes A1, D1 and D6 circulate in liver disease patients in Kenya, with A1 predominating.
Assuntos
Carcinoma Hepatocelular/virologia , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Cirrose Hepática/virologia , Neoplasias Hepáticas/virologia , Adulto , Sequência de Bases , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Estudos Transversais , DNA Viral/sangue , DNA Viral/genética , Feminino , Genótipo , Técnicas de Genotipagem , Antígenos de Superfície da Hepatite B/genética , Antígenos E da Hepatite B/genética , Vírus da Hepatite B/classificação , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/genética , Humanos , Quênia , Cirrose Hepática/diagnóstico , Cirrose Hepática/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Masculino , Filogenia , Regiões Promotoras Genéticas , Análise de Sequência de DNA , Carga ViralRESUMO
Blood samples were obtained from blood donors and patients with chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC) from provincial hospitals and Kenyatta National Hospital (KNH). Patients with chronic liver disease (CH, LC and HCC) underwent abdominal ultrasound screening as well. The blood samples were screened for Hepatitis B surface antigen (HBsAg), anti hepatitis C virus (Hep CV) antibodies and alpha fetoprotein (AFP). A total of 44665 blood samples from blood donors were screened for HBsAg between July 1991 and January 1993. Of these 4.1% were found to be HBsAg positive. A total of 983 samples were taken from chronic liver disease patients out of which 22.2% were found to be HBsAg positive. Sixty-three patients were found to have liver cirrhosis and 53 patients had HCC on ultrasound screening. Anti Hep CV antibodies were found in 4.3% (5/116) of patients with LC and HCC. AFP levels were found to be significantly higher in HCC patients than in LC patients, levels of above 200 ng/ml being diagnostic of HCC. Follow up of high risk patients, i.e. those with HBsAg positive, chronic liver disease, by ultrasound screening and AFP detection may be useful in the early detection of HCC.
