Ursodeoxycholic acid therapy in pediatric patients with progressive familial intrahepatic cholestasis

Low phospholipid associated cholelithiasis (LPAC) syndrome, first described in 2001, could be the causality in a significant number of young patients with cholelithiasis, who have a recurrence of symptoms despite cholecystectomy. A mutation of the ABCB4/MDR3 gene, causes a disruption in the translocation of phosphatidylcholine, resulting in bile acid mediated biliary tract injury. The ABCB4 gene is also implicated in other diseases such as progressive familial intrahepatic cholestasis type 3, which is greater in severity and tools like genotyping can aid the physician in prognostication, as well as determining the response to medical therapy. A few symptomatic patients develop features of biliary obstruction due to intrahepatic calculi, and they require interventions-which may be endoscopic or surgical in nature. Although a majority of patients with LPAC syndrome respond well to ursodeoxycholic acid (UDCA) therapy, close monitoring is warranted to keep a check on disease progression.

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

Medicina ◽

10.3390/medicina57080854 ◽

2021 ◽

Vol 57 (8) ◽

pp. 854

Author(s):

Safak Gül-Klein ◽

Robert Öllinger ◽

Moritz Schmelzle ◽

Johann Pratschke ◽

Wenzel Schöning

Keyword(s):

Liver Transplantation ◽

Liver Function ◽

Intrahepatic Cholestasis ◽

Pediatric Patients ◽

Extrahepatic Manifestations ◽

Long Term Outcome ◽

Progressive Familial Intrahepatic Cholestasis ◽

Long Term Follow Up

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.

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