Objectives: Among numerous factors which account for the pathogenesis of non-alcoholic steatohepatitis (NASH), hepatic mitochondrial beta-oxidation is considered to play a pivotal role. We performed a (13)C-based breath test with a medium-chain fatty acid to non-invasively assess total body beta-oxidation in patients with NASH and in healthy controls.
Methods: We performed a simplified (13)CO(2)-based breath test in 16 patients with histologically proven NASH and 24 healthy controls. One hundred milligrams of sodium (13)C-octanoate dissolved in 200 ml of water were orally administered and breath samples were collected before and during 3 h following administration. The samples were analysed for the cumulative (13)CO(2) recovery (%-cum-dose) by non-dispersive infrared spectrometry. Additionally, data of 69 patients who had undergone a C-octanoate breath test for the assessment of gastric emptying were retrospectively evaluated for the %-cum-dose.
Results: The cumulative (13)CO(2) recovery 3 h after the administration of the substrate did not differ among patients with NASH and controls (34.6 +/- 7.0% vs. 34.6 +/- 6.5%, P = 0.90). Compared with men, women yielded a significantly higher cumulative (13)CO(2) excretion in both controls (30.1 +/- 5.7% vs. 38.5 +/- 4.4%, P = 0.0008) and NASH patients (30.2 +/- 5.4% vs. 39.0 +/- 6.5%, P = 0.031). Forty-two of 69 patients (61%) of the gastric emptying group showed a normal gastric emptying rate. Among these patients, women also demonstrated a tendency for a higher (13)CO(2) recovery compared with men (P = 0.055). This was not the case in 27 patients with delayed gastric emptying (P = 0.47).
Conclusions: Though hepatic mitochondrial function might be impaired in patients with NASH, total beta-oxidation of octanoic acid remains normal. Gender-specific metabolic modifications seem to account for significant differences of the cumulative (13)CO(2) recovery in women and men. This may have further consequences for the appraisal of (13)C breath tests which involve octanoic acid. Further trials focusing on the assessment of body composition and energy expenditure could contribute essential further information.