RESUMO
BACKGROUND & OBJECTIVES: Hepatitis C virus (HCV) induces an immune response of the host, manifested by the formation of anti-HCV antibodies mediated by adaptive and innate immunity. Toll-like receptors (TLRs) play a pivotal role in innate immunity system. This study was aimed to investigate the promoter region polymorphism and expression of TLR3 gene in patients with chronic HCV infection. METHODS: Patients with chronic HCV infection (N=180) and an equal number of age-sex matched controls were included in the study. Patients positive for HCV-RNA were subjected to analysis of TLR3 polymorphism by direct sequencing of PCR products verified by comparing with the sequences reported in the National Centre for Biotechnology Information (NCBI) database (accession number: NT 022792). Expression of TLR3 gene was analyzed by semiquantitative RT-PCR using housekeeping ß-actin gene as the internal control. RESULTS: Polymorphisms at position -288G/A and -705A/G were identified. The results were significant in -705 allele (P=0.004) OR 2.79(1.46-5.42) and were associated with high risk of HCV infection. In silico sequence analysis showed the presence of ectropic viral integration site 1 encoded factor, in which G at -705 results in the loss of this site. The -7C/A polymorphism was not seen in our study cohort. The expression of TLR3 was upregulated in chronic HCV patients compared to healthy controls. INTERPRETATION & CONCLUSIONS: Polymorphism in the -705A/G allele at the promoter region of the TLR3 gene may predispose individual to HCV infection. However association of TLR3 expression with polymorphism of TLR3 promoter was not found.
Assuntos
Hepatite C Crônica/genética , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genética , Receptor 3 Toll-Like/genética , Receptor 3 Toll-Like/metabolismo , Adulto , Estudos de Coortes , Feminino , Hepacivirus/imunologia , Hepacivirus/patogenicidade , Hepatite C Crônica/imunologia , Hepatite C Crônica/virologia , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Estudos RetrospectivosRESUMO
OBJECTIVE: The study was designed to examine the hypothesis whether the course and severity of hepatitis E virus (HEV)-related liver disease is worse during pregnancy. METHOD: The prospective study included 1088 patients (550 pregnant; 538 nonpregnant) with clinically and biochemically confirmed acute viral hepatitis (AVH) or acute liver failure (ALF) and were subjected to a complete panel of hepatitis serology. RESULTS: In the pregnant cohort, HEV was the cause of infection in 80.36% (442/550) of cases, whereas non-HEV accounted for 19.63 (108/550) of cases. In the ALF pregnant group, the prevalence of HEV was observed in 73.38% (102/139) of cases, whereas other viruses accounted for 26.61% (37/139) of illness. Ninety-eight of 129 (75.96%) cases of HEV-infected pregnant women died, whereas non-HEV infection was responsible for only 31 of 129 (24.04%) cases' death in comparison. Serum viral load in the ALF group was also significantly higher than that in the AVH group in the pregnant (24578.6 ± 12410.3 vs. 6821.9 ± 1832.7, respectively) cohort and nonpregnant cohort (583.6 ± 187.34 vs. 298.68 ± 65.77, respectively). CONCLUSION: HEV infection has a higher incidence, more severe course, and greater mortality in the pregnant cohort than in the nonpregnant cohort.
Assuntos
Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/genética , Polimorfismo Genético , Receptores CCR5/genética , Adenina/administração & dosagem , Adenina/análogos & derivados , Alanina Transaminase/metabolismo , Genótipo , Antígenos de Superfície da Hepatite B/metabolismo , Homozigoto , Humanos , Índia , Lamivudina/administração & dosagem , Testes de Função Hepática , Mutação , Nucleosídeos/administração & dosagem , Nucleotídeos/administração & dosagem , Organofosfonatos/administração & dosagem , Projetos Piloto , Telbivudina , Timidina/administração & dosagem , Timidina/análogos & derivadosRESUMO
BACKGROUND AND AIM: Progression of hepatitis B virus infection (HBV) might be affected by host genetic factors. The present study was undertaken to study the role of glutathione S-transferases (GST)-M1 and T1 gene polymorphisms in different stages of HBV infection: HBV inactive carrier, chronic hepatitis B and cirrhosis, and cryptogenic cirrhosis. METHODS: The study population comprised of 170 subjects; 120 cases (HBV inactive carrier, n = 30; HBV related chronic hepatitis, n = 30; HBV related cirrhosis, n = 30; cryptogenic cirrhosis, n = 30) and 50 unrelated healthy adults without liver disease as controls. Analysis of GSTM1 and GSTT1 gene polymorphisms was done by multiplex polymerase chain reaction. RESULTS: The GSTM1 null genotype was seen more commonly in hepatitis B cirrhosis (n = 21; 70%), chronic hepatitis B (n = 19; 63.33%) and cryptogenic cirrhosis (n = 17; 56.67%) as compared with inactive carrier (n = 9; 30%) and controls (n = 13; 26%). The GSTT1 null genotype was seen less frequently in all the groups, the observed frequencies were controls (n = 7; 14%), inactive carrier (n = 5; 16.67%), chronic hepatitis B (n = 8; 26.67%) and hepatitis B cirrhosis (n = 7; 23.33%). The difference of GSTM1 null genotype frequencies was statistically significant for hepatitis B cirrhosis vs. controls (P = 0.0002), chronic hepatitis B vs. controls (P = 0.002) and cryptogenic cirrhosis vs. controls (P = 0.01). The GSTT1 null genotype was not found to vary significantly between the groups. CONCLUSION: The patients with GSTM1 null genotype are at risk of progression of liver disease as the frequency of GSTM1 null genotype was found to be significantly higher in chronic hepatitis B, hepatitis B cirrhosis and cryptogenic cirrhosis as compared with controls.