Metabolic profiles and liver steatosis in children with liver transplantation for progressive familial intrahepatic cholestasis type 1

Abstract

Aims: Severe liver steatosis is common complication post-transplantation in patient with progressive familial intrahepatic cholestasis type 1 (PFIC1). We aimed to evaluate metabolic profiles in children who received orthotopic liver transplantation (OLT) for PFIC1 and their correlation with the development of fatty liver disease (FLD). Methods: Patients transplanted for PFIC1 disease were identified and matched in a 1:2 ratio with patients transplanted for other indications. Liver biopsy was used to determine the presence of FLD. Lipid profiles were compared in the 2 groups. To investigate mechanistic pathways leading to the development of FLD, volatile organic compounds (VOCs) were analyzed on prospectively collected samples using a selective ion flow tube mass spectrometry. Results: Five children with PFIC1 disease and 10 children with other indications for liver transplantation were included. Liver biopsies demonstrated that all children with PFIC1 had moderate-to-severe steatosis. The PFIC1 group had significantly lower HDL (20.9±6.0 Ana Catalina Arce-Clachar1, Jonathan Moses1, Gursimran Kochlar1, Peggy George1, Vera Hupertz1, Kadakkal Radhakrishnan1, Raed Dweik1, Naim Alkhouri1 Affiliations: 1MD, Department of Pediatric Gastroenterology, Cleveland Clinic Children’s Hospital. Corresponding Author: Naim Alkhouri, MD, Department of Pediatric Gastroenterology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195. USA; Tel: 216-444-9000; Fax: 216-444-2974; Email: alkhoun@ccf. org Received: 18 December 2014 Accepted: 29 January 2015 Published: 08 April 2015 mg/dL versus 51.3±17.1 mg/dL, respectively, p < 0.001) and total cholesterol levels (72±8.0 versus 156±103, p < 0.001) post transplantation compared to the other group. VOCs, including acetaldehyde, ammonia and pentane were elevated in the PFIC1 group, while isoprene was lower. Conclusion: Fatty liver disease was a consistent finding in the patients with PFIC1 post OLT. Lipid levels were uniformly low in PFIC1 patients. Metabolomic analysis suggested that pathways in oxidative stress, gut bacteria production and cholesterol synthesis were different in children with PFIC1.