Effectively assessing subtle hepatic metabolic functions by novel non-invasive tests might be of clinical utility in scoring
NAFLD (
non-alcoholic fatty liver disease) and in identifying altered metabolic pathways. The present study was conducted on 39 (20 lean and 19 obese) hypertransaminasemic patients with histologically proven
NAFLD {ranging from simple steatosis to severe
steatohepatitis [NASH (non-
alcoholic steatohepatitis)] and
fibrosis} and 28 (20 lean and eight
overweight) healthy controls, who underwent stable
isotope breath testing ([(13)C]
methacetin and [(13)C]ketoisocaproate) for microsomal and mitochondrial liver function in relation to histology, serum hyaluronate, as a marker of
liver fibrosis, and body size. Compared with healthy subjects and patients with simple steatosis, NASH patients had enhanced
methacetin demethylation (P=0.001), but decreased (P=0.001) and delayed (P=0.006) ketoisocaproate decarboxylation, which was inversely related (P=0.001) to the degree of histological
fibrosis (r=-0.701), serum hyaluronate (r=-0.644) and body size (r=-0.485). Ketoisocaproate decarboxylation was impaired further in obese patients with NASH, but not in patients with simple steatosis and in
overweight controls. NASH and
insulin resistance were independently associated with an abnormal ketoisocaproate breath test (P=0.001). The cut-off value of 9.6% cumulative expired (13)CO(2) for ketoisocaproate at 60 min was associated with the highest prediction (positive predictive value, 0.90; negative predictive value, 0.73) for NASH, yielding an overall sensitivity of 68% and specificity of 94%. In conclusion, both microsomal and mitochondrial functions are disturbed in NASH. Therefore stable
isotope breath tests may usefully contribute to a better and non-invasive characterization of patients with
NAFLD.