900 13C-Methionine Breath Test to Assess Intestinal Failure Associated Liver Disease

Abstract

Oxidation of L[1-13 C]methionine ([ 13 C]-Met) in liver mitochondria can be quantified by measuring exhaled 13 CO 2 . We hypothesized that 13 CO 2 recovery after i.v. administered [ 13 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[1-13 C]-Met breath tests ([ 13 C]-MBTs), five of whom underwent repeat testing after clinical changes in liver function. Sterile, pyrogen-free [ 13 C]-Met was given i.v. Six breath samples collected during 120 min were analyzed for 13 CO 2 enrichment using isotope ratio mass spectrometry. Pediatric end-stage liver disease (PELD) scores were recorded, and total carbon dioxide (CO 2 ) production was measured by indirect calorimetry. Twenty-seven patients (median age = 5.3 mo) underwent a total of 34 [ 13 C]-MBTs without adverse events. Fourteen patients had documented liver biopsies (five with cirrhosis and nine with cholestasis or fibrosis). The Intestinal failure (IF) is a clinical condition in which the body is incapable of supporting growth and/or fluid and electrolyte homeostasis because of inadequate functional intestinal surface area. In the neonatal population, recent reports estimate an incidence of up to 0.7% in very low birth weight infants, and up to 1.1% in extremely low birth weight infants. The associated mortality of IF in very low birth weight infants is thought to be as high as 20% (1).The mainstay of modern medical therapy for IF is parenteral nutrition (PN), but unfortunately, this therapy can be accompanied by liver injury that is termed intestinal failure-associated liver disease (IFALD). The etiology of IFALD can be multifactorial, and beyond its association with PN, IFALD has been linked with prematurity, number of infectious episodes, ability to tolerate enteral nutrition, number of laparotomies, number of days on antibiotics, and other yet to be identified factors (2). Although liver biopsy remains the gold standard for the evaluation of IFALD, the invasive nature of this test precludes its use as a frequent measure of disease progression or recovery. Conventional static biochemical liver tests (transaminase, bilirubin, alkaline phosphatase and albumin plasma levels, or prothrombin time) have been used to assess injury and function but vary widely in specificity and sensitivity (7-9). For example, patients with IFALD with normal or mildly elevated bilirubin can often have cirrhosis as determined by liver biopsy (10).In recognition of these deficiencies, the Child-Turcotte and Pugh (CTP) scoring system was initially developed in 1964 to assess the severity of chronic liver disease (11) and more recently, another widely used scoring system, the model for end-stage liver disease (MELD), was developed using serum creatinine, international normalized ratio (INR), and bilirubin to predict survival in adult patients with chronic liver disease (12). The pediatric end-stage liver disease (PELD) score is similar ...