Ursodeoxycholic acid (UDCA) in the treatment of chronic cholestatic diseases.
Several studies suggest that UDCA treatment has beneficial effects in chronic cholestatic diseases. We designed a controlled trial to assess the efficacy and tolerance of UCDA in primary biliary cirrhosis (PBC): 73 patients received UDCA (13-15 mg/kg per day) and 73 a placebo. One side-effect required interruption of therapy in each group. The relative risk of treatment failure (doubling of the bilirubin level or occurrence of a severe complication of cirrhosis) was 3 times higher in the placebo group. Pruritus resolved in 40% of the patients of UDCA group vs 19% in placebo group. Biological and histological parameters significantly improved in the patients receiving UDCA. Unexpectedly, immune parameters, including IgM levels and anti-mitochondrial antibody titers, also improved. The Mayo risk score was significantly different between the two groups at one and two years, suggesting that UDCA could prolong survival in PBC. Recent studies suggest that UDCA could have immunoregulating properties. Abnormal MHC class I expression by hepatocytes, observed in PBC, was dramatically reduced by UDCA treatment. Cholestasis itself induces hepatic MHC expression: hepatocyte MHC class I expression was present in 6/6 cholestatic patients vs 0/8 control subjects. Experimental cholestasis in the rat induced MHC class I expression. Cyclosporin or corticosteroids had no effect on this overexpression, suggesting that an immune mechanism is not involved in this phenomenon. To assess the effect of bile acids on MHC expression, human hepatocytes were incubated with bile acids. Chenodeoxycholic acid (CDCA) (an endogenous bile acid) but not UDCA induced a dose-dependent MHC class I hyperexpression. UDCA suppressed the CDCA-induced MHC hyperexpression.(ABSTRACT TRUNCATED AT 250 WORDS)
Calmus
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Y
Service d'Hépatologie, Hôpital Saint-Antoine, Paris, France.
Poupon
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R
D000818:Animals; D002779:Cholestasis / Q000188:drug therapy* / Q000276:immunology; D002908:Chronic Disease; D015395:Histocompatibility Antigens Class I; D006801:Humans; D066298:In Vitro Techniques; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy / Q000276:immunology; D008285:Major Histocompatibility Complex; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
D015395:Histocompatibility Antigens Class I; D014580:Ursodeoxycholic Acid