THE NON-INVASIVE 13C-METHIONINE BREATH TEST DETECTS HEPATIC MITOCHONDRIAL DYSFUNCTION AS A MARKER OF DISEASE ACTIVITY IN NON-ALCOHOLIC STEATOHEPATITIS

Introduction: Mitochondrial dysfunction plays a central role in the general pathogenesis of non-alcoholic fatty liver disease (NAFLD), increasing the risk of developing steatosis and subsequent hepatocellular inflammation. We aimed to assess hepatic mitochondrial function by a non-invasive C-13-methionine breath test (MeBT) in patients with histologically proven NAFLD. Methods: 118 NAFLD-patients and 18 healthy controls were examined by MeBT. Liver biopsy specimens were evaluated according to the NASH scoring system. Results: Higher grades of NASH activity and fibrosis were independently associated with a significant decrease in cumulative C-13-exhalation (expressed as cPDR(%)). cPDR(1.5h) was markedly declined in patients with NASH and NASH cirrhosis compared to patients with simple steatosis or borderline diagnosis (cPDR1.5h: 3.24 +/- 1.12% and 1.32 +/- 0.94% vs. 6.36 +/- 0.56% and 4.80 +/- 0.88% respectively; p<0.001). C-13-exhalation further declined in the presence of advanced fibrosis which was correlated with NASH activity (r = 0.36). The area under the ROC curve (AU-ROC) for NASH diagnosis was estimated to be 0.87 in the total cohort and 0.83 in patients with no or mild fibrosis (F0-1). Conclusion: The C-13-methionine breath test indicates mitochondrial dysfunction in non-alcoholic fatty liver disease and predicts higher stages of disease activity. It may, therefore, be a valuable diagnostic addition for longitudinal monitoring of hepatic (mitochondrial) function in non-alcoholic fatty liver disease.