The characterisation of hepatic mitochondrial function in patients with non-alcoholic fatty liver disease (NAFLD) using the 13C-ketoisocaproate breath test

Abstract

Hepatic mitochondrial function (HMF) assessed by the 13C-ketoisocaproate breath test (13C-KICA BT) has been previously shown to be significantly associated with the severity of biopsy proven non-alcoholic fatty liver disease (NAFLD). However, it is uncertain whether any perturbation in HMF relates specifically to severity of liver disease or factors associated with metabolic syndrome within (NAFLD). Our aim was to investigate whether there was any change in HMF assessed by 13C-KICA BT in patients with NAFLD compared to control subjects, and to assess the factors that are independently associated with HMF. Methods. 77 patients with NAFLD and 11 healthy control subjects were studied. HMF was assessed using 13C-KICA BT and expressed as cumulative % 13C-dose recovered on breath over 1 h (cPDR over 1 h). Liver fat and fibrosis was assessed by transient elastography. Multivariable linear regression modelling was undertaken to test the independence of associations with HMF. Results. HMF (cPDR over 1 h) was lower in NAFLD compared to controls [13.4% (4.8) v. 21.0% (6.3); p < 0.0001)]. In NAFLD, HMF was lower in patients with diabetes versus no diabetes [12.7% (3.4) v. 14.3% (6.1); p = 0.003)]. Regression modelling showed age (β = -0.08; p = 0.01), waist circumference (β = -0.08; p = 0.01), hip circumference (β = -0.04; p = 0.01), aspartate aminotransferase (AST) (β = -0.05; p = 0.01) and diabetes status (β = -1.81; p = 0.01) were independently associated with HMF (R2 = 41.5%; p < 0.0001). Conclusions. In patients with NAFLD (compared to healthy subjects), there was a reduction in HMF assessed by the 13C-KICA BT. Furthermore, in patients with NAFLD, HMF is independent and inversely associated with age, waist and hip circumference, AST and diabetes status.