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

Abstract

Oxidation of L[1-13C]methionine ([13C]-Met) in liver mitochondria can be quantified by measuring exhaled 13CO2. We hypothesized that 13CO2 recovery after i.v. administered [13C]-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[1-13C]-Met breath tests ([13C]-MBTs), five of whom underwent repeat testing after clinical changes in liver function. Sterile, pyrogen-free [13C]-Met was given i.v. Six breath samples collected during 120 min were analyzed for 13CO2 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 [13C]-MBTs without adverse events. Fourteen patients had documented liver biopsies (five with cirrhosis and nine with cholestasis or fibrosis). The [13C]-MBT differentiated patients with and without cirrhosis (medians 210 and 350, respectively, p = 0.04). Serial [13C]-MBTs in five patients reflected changing PELD scores. i.v. administering the stable isotope [13C]-Met with serial breath sampling provides a useful, safe, and potentially clinically relevant evaluation of hepatic function in pediatric IFALD. The [13C]-MBT may also help quantify progression or improvement of IFALD.

Utility of Aminotransferase/Platelet Ratio Index to Predict Liver Fibrosis in Intestinal Failure–Associated Liver Disease in Pediatric Patients

“…Because of all the mentioned factors, there is a need for a test or marker that allows identification of patients with IFALD progression, in order to avoid repeating LBX unnecessarily. In that respect, the PELD score, 1‐13C‐methionine breath test, and transient elastography were tested, but the correlation with liver fibrosis was low or the test was too complex to perform 29 – 33 . In addition, Kaufman et al 34 evaluated the possibility of predicting liver disease progression using 3 factors: albumin level, platelet count, and total bilirubin level.…”

European guideline on indications, performance and clinical impact of 13C‐breath tests in adult and pediatric patients: An EAGEN, ESNM, and ESPGHAN consensus, supported by EPC

“…Given that, as yet, few studies have been performed involving small groups of children with rare diseases, 178–181 the use of 13 C‐LFBT for clinical purposes cannot be recommended in the pediatric population, so far.…”

“…For instance, the effect of transarterial chemoembolization on liver function has been monitored by 13 C-methacetin test, 174 and several studies suggest that this test could also be used for planning of hepatic resections. [175][176][177] Given that, as yet, few studies have been performed involving small groups of children with rare diseases, [178][179][180][181] the use of 13 As discussed before, potential confounders of test results detailed in general methodology have to be avoided. For 13 C-LFBT that investigate cytochrome P 450 enzymes, drugs with potential influence on cytochrome P 450 metabolism are of particular relevance, [182][183][184] and it may be necessary to perform a test despite ongoing medication.…”

The prevalence of liver fibrosis according to non-invasive tools in a pediatric home parenteral nutrition cohort

“…In future trials, international collaboration is needed to assess a large cohort of patients with longitudinal follow-up and serial measurements to correlate non-invasive tests with liver outcome. Other non-invasive modalities, such as MRI modalities and 13C-Methionine breath test should also be investigated since these show promising results in assessing pediatric IFALD [47,48].…”