RESUMO
WHAT IS KNOWN AND OBJECTIVE: Anti-tuberculosis drugs (ATD), although highly effective, often cause liver injury. Glutathione S-transferases (GST) play a crucial protective role in the detoxifying mechanisms of drugs. Several studies have investigated the genetic null variants of GSTM1 and GSTT1 as possible risk factors for ATD-induced liver injury; however, those findings are inconsistent. We investigated GSTM1 and GSTT1 null genotypes in Brazilian patients with tuberculosis (TB), adjusting for other possible predictors of ATD-induced liver injury. METHODS: This was a prospective cohort study with patients who were treated for TB from 2006 to 2011. GSTM1 and GSTT1 gene deletions were analysed from genomic DNA by polymerase chain reaction (PCR). Demographic, clinical and laboratory data were extracted from medical records and possible predictors of liver injury were evaluated. RESULTS AND DISCUSSION: This study enrolled 177 patients. Anti-tuberculosis drugs-induced liver injury incidence was 33.3%. Hepatitis B infection (HBV) and increased alanine aminotransferase (ALT) baseline were significant predictors. Neither GSTM1 nor GSTT1 null genotypes were associated with ATD-induced liver injury; nevertheless, the comparison among four different liver toxicity grades showed that GSTM1 non-null genotype was significant more frequent among the higher grades of liver toxicity. WHAT IS NEW AND CONCLUSION: GSTM1 and GSTT1 null genotypes do not seem to play important roles in ATD-induced liver injury in Brazilians. However, there was evidence that GSTM1 polymorphisms were possibly related to the intensity of toxicity. Active HBV and initial high ALT could predict ATD-induced liver injury.
Assuntos
Antituberculosos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Glutationa Transferase/genética , Adulto , Brasil/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/genética , Estudos de Coortes , Feminino , Deleção de Genes , Predisposição Genética para Doença , Genótipo , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo Genético , Estudos Prospectivos , Fatores de Risco , Tuberculose/tratamento farmacológicoRESUMO
BACKGROUND: Liver toxicity due to tuberculosis (TB) treatment is a frequent cause of treatment interruption, and may sometimes lead to a change in therapy to a less potent regimen. OBJECTIVE: To estimate the risk of hepatotoxicity in patients with or without hepatitis B virus (HBV) infection receiving TB treatment and to develop a clinical prediction rule. DESIGN: A prospective observational follow-up was conducted. Data from 154 patients who underwent TB treatment were analysed. Crude risk ratios were estimated and a Cox proportional hazards model was fit. RESULTS: The mean follow-up time was 187 days. Crude risk ratios showed that ethnicity, human immunodeficiency virus infection, multiple sexual partners, highly active antiretroviral treatment, and clinical forms of TB were possible predictors of liver toxicity. HBV infection and other sexually transmitted diseases showed considerable relative risk, although not statistically significant. The Cox proportional hazards model identified the following predictors of hepatotoxicity: White ethnicity, multiple sexual partners, high baseline alanine transferase and clinical forms of TB. Active HBV, indicated by the detection of surface antigen HBV, could predict hepatotoxicity, although with low precision. CONCLUSION: Using this information, we were able to apply a score and draw a nomogram to estimate survival probabilities and median times to event for each patient.