Trials of ursodeoxycholic acid for the treatment of primary biliary cholangitis (primary biliary cirrhosis)
- Steven Flamm, MD
Steven Flamm, MD
- Chief, Liver Transplantation Program
- Professor of Medicine
- Feinberg School of Medicine
- Northwestern University
- Raoul Poupon, MD
Raoul Poupon, MD
- Professor of Hepatology and Gastroenterology
- University Pierre et Marie Curie
- UPMC, Sorbonne University, Paris, France
Ursodeoxycholic acid (UDCA) was proposed as a potential therapy for cholestatic liver disease based on the following rationales: accumulation of toxic bile acids might be at least partially responsible for liver injury in chronic cholestasis, and replacement of endogenous bile acids by a non-toxic bile acid (UDCA) might protect the liver and retard the progression of these disorders. In preliminary studies of patients with primary biliary cholangitis (PBC; previously referred to as primary biliary cirrhosis) , UDCA was found to provide marked improvement in liver tests, leading to randomized trials and meta-analyses that also found a benefit. UDCA is generally well tolerated. Side effects may include headache, weight gain , constipation, and diarrhea.
Experimental and clinical evidence suggest that at least four mechanisms of action are involved in the beneficial therapeutic effects of UDCA in cholestatic disorders :
●An increased hydrophilicity index of the circulating bile acid pool
●Stimulation of hepatocellular and ductular secretions
●Cytoprotection against bile acid- and cytokine-induced injury
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