P-82 URSODEOXYCHOLIC ACID AND/OR CIPROFIBRATE FOR TREATING PATIENTS WITH PRESUMPTIVE DIAGNOSIS OF LOW PHOSPHOLIPID CHOLELITHIASIS, A CLINICAL SPECTRUM OF PROGRESSIVE FAMILIAL INTRAHEPATIC CHOLESTASIS TYPE 3

Abstract

Introduction: Low Phospholipid-Associated Cholelithiasis (LPAC) is a clinical spectrum of Progressive Familial Intrahepatic Cholestasis type 3 (PFIC3), with mutations in the ABCB4 gene, reduced levels of phosphatidylcholine in bile, formation of cholesterol gallstones, damage of bile ducts epithelium and cholestasis. Ursodeoxycholic acid (UDCA) is effective and fibrates may also be used to activate PPAR-α receptor, inducing bile secretion of phosphatidylcholine. Aim: Retrospectively evaluate efficacy and safety of ciprofibrate in LPAC/PFIC3. Method: Diagnosis of PFIC3 was confirmed by detection of mutations of ABCB4 gene. LPAC diagnosis was suggested by 2 out of 5 criteria: biliary symptoms before 40 years; recurrence after cholecystectomy; intrahepatic lithiasis; cholelithiasis in first‐degree relatives; intrahepatic cholestasis of pregnancy or contraceptive‐induced cholestasis. Enzymes, liver function and pruritus were analyzed after 3, 6 and 12 months of UDCA and after ciprofibrate 100mg/day using the Wilcoxon test. Results: 27(93%) patients with clinical diagnosis of LPAC and 2 of PFIC3. 23 (79%) female with mean age at onset of symptoms of 26.7±13.6 years. 23(80%) had family history of biliary disease; 22(76%) cholelithiasis before 40 years; 7(24%) intrahepatic lithiasis. 22/29 (78%) received ciprofibrate after 4.5±4.9 months of UDCA use, in a mean dose of 13.1±2.2mg/kg/day. During UDCA there was a significant decrease in aminotransferases, alkaline phosphatase(AP) and gamma-glutamyltransferase(GGT) levels, without significant improvement in the liver function. After addition of fibrate, pruritus disappeared in all 7 patients, with significant improvement of AP, GGT and albumin in the third month. There was no significant renal dysfunction. Fibrate was discontinued in 8: 1 liver transplantation, 2 irregular use, 5 side effects. 27 patients are still in follow up. Conclusion: Ciprofibrate was beneficial to improve pruritus and laboratory tests in LPAC/PFIC3 after partial response with UDCA. Fibrate therapy was safe and well tolerated.