P22\u2005Fibrates: an adjuvant therapy for cholestasis in paediatric age group

Abstract

Introduction Bile formation is a delicate process. This is illustrated by inherited liver diseases caused by mutations affecting hepatocanalicular transporters. It leads to intrahepatic accumulation of toxic bile acids with clinical features including pruritus, malabsorption and vitamin deficiencies. Chronic cholestasis leads to liver fibrosis which can progress to cirrhosis and end-stage liver disease. Effective treatment of these transport defects is a clinical and scientific challenge.1 Fibrates were first noted to reduce hepatic alkaline phosphatase (ALP) isoenzyme levels during their development as cholesterol-lowering agents in the 1970s, which appeared to be related to their effect on peroxisome proliferator activated receptor PPAR-α receptor. Since then, several case reports and pilot studies have demonstrated the efficacy of fibrates in reducing serum biomarkers of cholestasis in patients with incomplete response to ursodeoxycholic acid(UDCA)monotherapy.2 Aim To assess the effect of fenofibrates on pruritus and biochemical laboratory values in children with none-obstructive cholestatic liver diseases. Subject and Methods A prospective study, included 71 paediatric patients suffering from non-obstructive cholestatic liver diseases. They were recruited from outpatient clinics at The National Liver Institute, Menoufia University, Egypt and Dr.Yassin Abdel Ghaffar Charity Centre for Liver Diseases & Researches, Cairo, Egypt. Patients were divided into 2 groups: Therapy group (T-group): Received UDCA, 10–30 mg/kg/d orally and Fenofibratein (FF) 10–20 mg/kg orally, once per day. This group included 23 patients. Control group (C-group): Received UDCA acid 10–30 mg/kg/d by oral rout and included 30 patients. Informed consents were obtained from the patients or careers and the study was registered as a clinical trial. Both groups were followed up for 4 months with regular review visits at zero, 1 month and 4 months with the following data: Full history taking including the points of the pruritus grading score (PGS), Thorough clinical examination with stress on presence of pruritus marks Investigations: Liver function tests and FBC with every visit Total serum bile acids, lipid profile and abdominal ultrasound at the start of the study and after 4 months. Endpoints were defined: Four months’ follow up visit (± 2 weeks) 2- Developing serious side effects that needed change in their therapy (increased PGS, ALT or bilirubin >1.5x baseline). The changes in all parameters and discontinuation rates in the two groups were compared after one and four months of the therapy. Results In total 71 patients were included in the study, 18 patients of them lots follow up during the study, while 53 continued. There were no significant differences in the baseline demographic and biochemical baseline data between the two groups (P>0.05). After one month, there was statistically significant difference between the two groups in the PGS as it decreased by After four months, there were statistically significant between the 2 groups regarding decreased ALT levels below 1.5x base line levels, AST, GGT and bile acid levels in favour of the T-group (P Summary and Conclusion The use of FF in combination with UDCA provided satisfactory clinical outcomes, which could be a promising alternative, but patients should be monitored closely as side effects may occur despite achieving improvements in pruritus. References Fuchs CD, Halilbasic E, Trauner M. 2017. Novel treatments targeting metabolic and signaling mechanisms in primary biliary cholangitis. Clinical Liver Disease, 9, 43–47. Ghonem NS, Boyer JL. 2013. Fibrates as adjuvant therapy for chronic cholestatic liver disease: its time has come. Hepatology, 57,1691–1693.