Chronic Cholestasis Clinical Trial
Official title:
Fibrates: An Adjuvant Therapy for Cholestasis In Pediatric Age Group
A study conducted to assess the effect of fibrates on pruritus and biochemical picture in pediatric patients with cholestatic liver diseases.
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.
;