[13C]Methionine breath test to assess intestinal failure-associated liver disease.

Oxidation of L[1-C]methionine ([C]-Met) in liver mitochondria can be quantified by measuring exhaled CO2. We hypothesized that CO2 recovery after i.v. administered [C]-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]-Met breath tests ([C]-MBTs), five of whom underwent repeat testing after clinical changes in liver function. Sterile, pyrogen-free [C]-Met was given i.v. Six breath samples collected during 120 min were analyzed for CO2 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 mo) underwent a total of 34 [C]-MBTs without adverse events. Fourteen patients had documented liver biopsies (five with cirrhosis and nine with cholestasis or fibrosis). The [C]-MBT differentiated patients with and without cirrhosis (medians 210 and 350, respectively, p = 0.04). Serial [C]-MBTs in five patients reflected changing PELD scores. i.v. administering the stable isotope [C]-Met with serial breath sampling provides a useful, safe, and potentially clinically relevant evaluation of hepatic function in pediatric IFALD. The [C]-MBT may also help quantify progression or improvement of IFALD.