Labeled breath tests in patients with NASH: Octanoate oxidation relates best to measures of glucose metabolism.

In vivo methods to estimate human liver mitochondrial activity are lacking and this project's goal was to use a non-invasive breath test to quantify complete mitochondrial fat oxidation and determine how test results changed when liver disease state was altered over time. Patients with suspected non-alcoholic fatty liver disease (NAFLD; 9 men, 16 women, 47 ± 10 years, 113 ± 23 kg) underwent a diagnostic liver biopsy and liver tissue was histologically scored by a pathologist using the NAFLD activity score (0-8). To assess liver oxidation activity, a labeled medium chain fatty acid was consumed orally (23.4 mg ¹³ C ₄ -octanoate) and breath samples collected over 135 min. Total CO ₂ production rates were measured using breath ¹³ CO ₂ analysis by isotope ratio mass spectrometry. Fasting endogenous glucose production (EGP) was measured using an IV infusion of ¹³ C ₆ -glucose. At baseline, subjects oxidized 23.4 ± 3.9% (14.9%-31.5%) of the octanoate dose and octanoate oxidation (OctOx) was negatively correlated with fasting plasma glucose ( r = -0.474, p = 0.017) and EGP ( r = -0.441, p = 0.028). Twenty-two subjects returned for repeat tests 10.2 ± 1.0 months later, following lifestyle treatment or standardized care. OctOx (% dose/kg) was significantly greater across all subjects ( p = 0.044), negatively related to reductions in EGP ( r = -0.401, p = 0.064), and tended to correlate with reduced fasting glucose ( r = -0.371, p = 0.090). Subjects exhibited reductions in steatosis ( p = 0.007) which tended to correlate with increased OctOx (% of dose/kg, r = -0.411, p = 0.058). Based on our findings, the use of an ¹³ C-octanoate breath test may be an indicator of hepatic steatosis and glucose metabolism, but these relationships require verification through larger studies in NAFLD populations.
Competing Interests: Author AD was empolyed by Boyce & Bynum Pathology Professional Services. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Mucinski, Perry, Fordham, Diaz-Arias, Ibdah, Rector and Parks.)