RESUMEN
Mannose binding lectin (MBL) is a molecule of the innate immunity, which activates the complement system and modulates inflammation. We investigated the association of the polymorphisms in the exon 1 and promoter region of the MBL gene (MBL2) with the susceptibility to hepatitis C virus (HCV) infection and the degree of liver fibrosis in Brazilian patients chronically infected with HCV. The study was performed in 232 healthy control subjects and 186 patients, 157 of whom underwent liver biopsy after histopathology analysis and classification of fibrosis according to Metavir score. Exon 1 was genotyped by melting temperature assay and the promoter region by Taqman real-time polymerase chain reacation. The frequency of genotypes related to low production of MBL was higher in patients with HCV than in controls (p(c) = 0.0001, odds ratio = 3.52; confidence interval = 1.86-6.71). In addition, the frequency of variant haplotype, HYO was higher in patients with the severe fibrosis stage F4 (10.7%) than in patients with the mild/moderate fibrosis stage F1/F2 (3.4%), when compared with the HYA haplotype (p(c) = 0.04, odds ratio = 5.25, confidence interval = 1.11-23.62). We conclude that MBL variant alleles expressing low levels of MBL are associated with the susceptibility to HCV infection and that the inheritance of HYO haplotype could be associated with fibrosis severity.
Asunto(s)
Hepatitis C/complicaciones , Hepatitis C/genética , Cirrosis Hepática/etiología , Cirrosis Hepática/genética , Lectina de Unión a Manosa/genética , Adulto , Anciano , Brasil , Exones/genética , Femenino , Frecuencia de los Genes/genética , Genotipo , Haplotipos/genética , Hepacivirus/genética , Heterocigoto , Homocigoto , Humanos , Cirrosis Hepática/diagnóstico , Masculino , Lectina de Unión a Manosa/sangre , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Regiones Promotoras Genéticas/genética , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
AIM: There is no proven medical therapy for the treatment of non-alcoholic steatohepatitis (NASH). Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. The aim of our study was to evaluate the efficacy of N-acetylcysteine (NAC) in combination with metformin (MTF) in improving the aminotransferases and histological parameters (steatosis, inflammation, hepatocellular ballooning, and fibrosis) after 12 months of treatment. METHODS: Twenty consecutive patients (mean age 53 +/- 2 years [36-68] and body mass index [BMI] 29 [25-35]) with biopsy-proven NASH were enrolled in the study. NAC (1.2 g/day) and MTF (850-1000 mg/day) were given orally for 12 months. All patients underwent evaluation of serum aminotransferases, fasting lipid profile and serum glucose, anthropometric parameters, and nutritional status at 0 and 12 months. A low calorie diet was prescribed for all patients. RESULTS: Serum alanine aminotransferase, high-density lipoprotein, insulin, and glucose concentrations and thehomeostasis model assessment-insulin resistance (HOMA-IR) index were reduced significantly at the end of study (P < 0.05). The BMI declined, but without statistical significance. Aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, cholesterol, and triglycerides levels were not altered with the treatment. Liver steatosis and fibrosis decreased (P < 0.05), but no improvement was noted in lobular inflammation or hepatocellular ballooning. The NASH activity score was significantly improved after treatment. CONCLUSION: Based on the biochemical and histological evidence in this pilot study, NAC in combination with MTF appears to ameliorate several aspects of NASH, including fibrosis. Further studies of this form of combination therapy are warranted to assess its potential efficacy.
