Fibrates in Pediatric Cholestasis

Cholestatic liver disorders include a spectrum of hepatobiliary diseases of diverse etiologies that are characterized by impaired hepatocellular secretion of bile, resulting in accumulation of bile acids, bilirubin and cholesterol.This could result in different clinical features including pruritus, malabsorption and vitamin deficiencies with subsequent coagulation disorders and bone disease. Persistence of cholestasis leads to biliary fibrosis which can progress to liver cirrhosis and end-stage liver disease.

Nuclear receptors (NRs) regulate ligand-activated transcription factor networks of genes for the elimination and detoxification of potentially toxic biliary constituents accumulating in cholestasis. Activation of several NRs also modulates fibrogenesis, inflammation, and carcinogenesis as sequelae of cholestasis. Hence, It represent attractive targets for pharmacotherapy of cholestatic disorders.

Several already available drugs may exert their beneficial effects in cholestasis via NR activation eg, ursodeoxycholic acid via glucocorticoid receptor and pregnane X receptor, and rifampicin via pregnane X receptor. Unfortunately, Some patients may not respond to these medications.

Fibrates, serum Lipid lowering medication, has a stimulation action on proliferator activated receptor alpha. It is a nuclear receptor with an integral role in bile homeostasis. Several case reports and pilot studies have demonstrated the efficacy of fibrates in reducing serum biomarkers of cholestasis and liver function abnormalities in patients with incomplete response to ursodeoxycholic acid monotherapy. These results are of interest, because fibrates are attracting increased attention as adjunct therapy for chronic cholestatic liver diseases.

Inclusion criteria

• Patient with chronic cholestatic liver disease defined as any condition in which substances normally excreted into bile are retained for more than 6 months.

Exclusion criteria

• Patients with anatomical or mechanical obstructive causes for cholestasis.
• Cholestatic patients who were suffering from another liver disease.
• Cholestatic patients who were receiving drugs affecting lipid profile.
• Patients receiving drugs that interact with Fenofibrate (FF) e.g statins and warfarin
• Patients with non obstructive gall bladder stones were excluded from T gp.