European mitochondrial DNA haplogroups and liver fibrosis in HIV and hepatitis C virus coinfected patients

Abstract

HIV infection, hepatitis C virus (HCV) liver disease, and mitochondrial DNA (mtDNA) polymorphisms are three possibly interrelated factors that might be associated with progression of liver disease. The aim of this study was to investigate whether mtDNA haplogroups had any influence on liver fibrosis progression in HIV/HCV coinfected patients. We carried out a cross-sectional study in 231 patients who were genotyped via Sequenom's MassARRAY platform (San Diego, California, USA). Liver fibrosis was estimated based on the METAVIR score. In each patient, fibrosis progression rate (FPR) was calculated by dividing the fibrosis stage (0-4) by the estimated duration of HCV infection in years. The cluster or major haplogroup HV was significantly associated with reduced odds ratios (OR) for advanced fibrosis [OR 0.35, 95% confidence interval (CI) 0.16-0.77, P = 0.009], cirrhosis (OR 0.16, 95% CI 0.04-0.60, P = 0.007), or high FPR (OR 0.43, 95% CI 0.21-0.84, P = 0.015). Within the major haplogroup HV, haplogroup H was significantly associated with an absence of advanced fibrosis (OR 0.40, 95% CI 0.18-0.91, P = 0.029), cirrhosis (OR 0.14, 95% CI 0.03-0.67, P = 0.014), or high FPR (OR 0.47, 95% CI 0.23-0.95, P = 0.035). We also found a significant association with increased odds of cirrhosis (OR 5.25, 95% CI 1.76-15.64, P = 0.003) in the closely related major haplogroup U. The mtDNA haplogroups HV and H were associated with slower fibrosis progression, and the haplogroup U was associated with faster fibrosis progression in HIV/HCV coinfected patients. These data suggest that mtDNA haplogroup may play a significant role in liver fibrogenesis during HCV infection.