[13C]Methionine Breath Test to Assess Intestinal Failure-Associated Liver Disease

Oxidation of L[1-C-13]methionine ([C-13]-Met) in liver mitochondria can be quantified by measuring exhaled (CO2)-C-13. We hypothesized that (CO2)-C-13 recovery after i.v. administered [C-13]-Met would provide a noninvasive measure of liver function in pediatric intestinal failure-associated liver disease (IFALD). After Institutional Review Board (IRB) approval, 27 patients underwent L[1-C-13]-Met breath tests ([C-13]-MBTs), five of whom underwent repeat testing after clinical changes in liver function. Sterile, pyrogen-free [C-13]-Met was given i.v. Six breath samples collected during 120 min were analyzed for (CO2)-C-13 enrichment using isotope ratio mass spectrometry. Pediatric end-stage liver disease (PELD) scores were recorded, and total carbon dioxide (CO2) production was measured by indirect calorimetry. Twenty-seven patients (median age = 5.3 mu) underwent a total of 34 [C-13]-MBTs without adverse events. Fourteen patients had documented liver biopsies (five with cirrhosis and nine with cholestasis or fibrosis). The [C-13]-MBT differentiated patients with and without cirrhosis (medians 210 and 350, respectively, p = 0.04). Serial [C-13]-MBTs in five patients reflected changing PELD scores. i.v. administering the stable isotope [C-13]-Met with serial breath sampling provides a useful, safe, and potentially clinically relevant evaluation of hepatic function in pediatric IFALD. The [C-13]-MBT may also help quantify progression or improvement of IFALD. (Pediatr Res 68: 349-354, 2010)