Total body metabolism of 13C-octanoic acid is preserved in patients with non-alcoholic steatohepatitis, but differs between women and men

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 C-13-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 (CO2)-C-13-based breath test in 16 patients with histologically proven NASH and 24 healthy controls. One hundred milligrams of sodium C-13-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 (CO2)-C-13 recovery (%-cum-dose) by non-dispersive infrared spectrometry. Additionally, data of 69 patients who had undergone a 13C-octanoate breath test for the assessment of gastric emptying were retrospectively evaluated for the %-cum-dose. Results The cumulative (CO2)-C-13 recovery 3 h after the administration of the substrate did not differ among patients with NASH and controls (34.6 +/- 70% VS. 34.6 +/- 6.5%, P= 0.90). Compared with men, women yielded a significantly higher cumulative (CO2)-C-13 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 (CO2)-C-13 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 (CO2)-C-13 recovery in women and men. This may have further consequences for the appraisal of C-13 breath tests which involve octanoic acid. Further trials focusing on the assessment of body composition and energy expenditure could contribute essential further information.