Longitudinal effects of hepatitis C virus treatment on hepatic mitochondrial dysfunction assessed by 13C-methionine breath test

Background Hepatitis C virus (HCV) infection is characterized by remarkable levels of oxidative stress induced by virus interactions with hepatic mitochondria. Aim To examine hepatic mitochondrial function in HCV-infected patients assessed by a non-invasive C-13-methionine breath test (MeBT) and to explore longitudinal effects of antiviral treatment. Methods Twenty-one patients with chronic hepatitis C undergoing antiviral treatment with pegIFN alpha and ribavirin and 20 healthy controls were studied. MeBT was performed at baseline, week 12, end-of-treatment and after 24 weeks of follow-up in all patients with early virological response (n = 15). Results Twelve patients achieved sustained virological response (SVR); three patients relapsed for HCV-RNA replication. Cumulative percentage C-13- exhalation (cPDR(1.5h)) was significantly decreased in HCV-infected individuals compared to controls irrespective of genotype and Fibrosis stage (P < 0.001). Antiviral treatment induced a further decay in cPDR(1.5h) (P < 0.01). After treatment cessation, C-13-exhalation returned at least to baseline values in all patients. SVR was even associated with a mean cPDR(1.5h) increase of 70% compared to baseline. Conclusions Hepatitis C virus infection and antiviral treatment synergistically impair hepatic mitochondrial function, which may return to normal after sustained virus elimination. MeBT may be a valuable diagnostic instrument for monitoring hepatic mitochondrial function in particular in patients with mitochondrial comorbidities.