Treatment of Primary Biliary Cirrhosis with Ursodeoxycholic Acid, Budesonide and Fibrates

Abstract

Long-term treatment with ursodeoxycholic acid (UDCA; 13–15 mg/kg/day) in patients with primary biliary cirrhosis (PBC) improves biochemical liver tests, delays histological progression and prolongs survival without liver transplantation. UDCA monotherapy appears sufficient for many patients as suggested by long-term observational data. However, the transplant-free survival rate of UDCA-treated patients remains significantly lower than that of an age- and sex-matched control population. Therefore, there is a continued need for new therapeutic options in PBC. In this article we review and discuss the following issues: the appropriate selection of patients requiring new therapeutic options, the role of budesonide in the management of these patients, and the emerging place of peroxisome proliferator-activated receptor-α ligands as anti-inflammatory and immunomodulating agents in PBC.

Review article: overlap syndromes and autoimmune liver disease

“… In PBC, a degree of parenchymal inflammation may be observed secondary to bystander, collateral hepatocellular injury. In such cases with ‘florid’ interface hepatitis, there is anecdotal data demonstrating the efficacy of immunosuppression, particularly budesonide . However, these studies are not yet supported by well‐controlled, double‐blind, randomised trials. …”

Changing outcomes with antiviral or antifibrotic therapies

“…It is important to stress that no studies indicate a primary antifibrotic effect of ursodeoxycholic acid in the liver. However, a variety of reports suggest that ursodeoxycholic acid may delay progression of fibrosis in primary biliary cirrhosis through its effects on biliary ductal inflammation, particularly if initiated early in the course of the disease [71].…”

Nuclear Receptors as Drug Targets in Cholestatic Liver Diseases

“…Activation of GR by glucocorticoids is widely used to treat inflammatory and autoimmune diseases 222 and have also been tested for treatment of various cholestatic disorders including PBC 223 . Notably, in addition to their classic anti-inflammatory and immunomodulatory effects, GR ligands may also have anti-cholestatic effects through modulation of transporters.…”