Long-Term Outcome after Liver Transplantation for Progressive Familial Intrahepatic Cholestasis

Abstract

Background and Objectives: Progressive familial intrahepatic cholestasis (PFIC) is a rare autosomal recessive inherited disease divided into five types (PFIC 1-5). Characteristic of all types is early disease onset, which may result clinically in portal hypertension, fibrosis, cirrhosis, hepatocellular carcinoma (HCC), and extrahepatic manifestations. Liver transplantation (LT) is the only successful treatment approach. Our aim is to present the good long-term outcomes after liver transplantation for PFIC1, focusing on liver function as well as the occurrence of extrahepatic manifestation after liver transplantation. Materials and Methods: A total of seven pediatric patients with PFIC1 underwent liver transplantation between January 1999 and September 2019 at the Department of Surgery, Charité Campus Virchow Klinikum and Charité Campus Mitte of Charité-Universitätsmedizin Berlin. Long-term follow-up data were collected on all patients, specifically considering liver function and extrahepatic manifestations. Results: Seven (3.2%) recipients were found from a cohort of 219 pediatric patients. Two of the seven patients had multilocular HCC in cirrhosis. Disease recurrence or graft loss did not occur in any patient. Two patients (male, siblings) had persistently elevated liver parameters but showed excellent liver function. Patient and graft survival during long-term follow-up was 100%, and no severe extrahepatic manifestations requiring hospitalization or surgery occurred. We noted a low complication rate during long-term follow-up and excellent patient outcome. Conclusions: PFIC1 long-term follow-up after LT shows promising results for this rare disease. In particular, the clinical relevance of extrahepatic manifestations seems acceptable, and graft function seems to be barely affected. Further multicenter studies are needed to analyze the clinically inhomogeneous presentation and to better understand the courses after LT.

Long-Term Results of Pediatric Liver Transplantation for Progressive Familial Intrahepatic Cholestasis

“…Besides, steatohepatitis after LT could lead to cirrhosis and require re-transplantation. Our study and several previous studies show that LT improves symptoms and survival rate irrespective of PFIC subtypes [ 6 , 8 , 10 ]. Due to the dysfunction of SLC10A2 in the apical membrane of PFIC type I patients, bile acid reabsorption in the intestine is disrupted, especially when the explanted graft starts to produce and secrete a normal volume of bile acids after LT [ 19 ].…”

“…With the development of surgical skills and perioperative management, the survival rate and life quality of PFIC patients after LT has significantly improved. As reported, the 10-year patient survival rate after LT ranged from 72.7% to 90.9%, varying among PFIC subtypes and operation centers [ 8 , 9 , 10 , 11 , 12 , 13 ]. Among them, PFIC type I patients suffered a relatively lower 10-year survival rate than other PFIC types, as low as 58% in a study [ 9 ].…”

Liver Transplantation for Hepatocellular Carcinoma in Patients with Inherited Metabolic Liver Diseases: A Single-Center Analysis

“… 8 The liver injury is usually precipitated by the accumulation of a toxic metabolite within the liver with associated chronic liver injury, which may progress to cirrhosis and subsequently to HCC. 9 , 10 The “toxic metabolite” theory of liver injury is exemplified by the accumulation of alpha 1 anti-trypsin within the endoplasmic reticulum of hepatocytes with resultant hepatocyte injury in patients with alpha 1 anti-trypsin deficiency. 11 Non-alcoholic steatohepatitis, a spectrum of liver disease seen in patients with metabolic syndrome, also progresses to cirrhosis and even HCC.…”