Triple therapy with ursodeoxycholic acid, prednisone and azathioprine in primary biliary cirrhosis: a 1-year randomized, placebo-controlled study

Wolfhagen, Frank H.J.; Hoogstraten, H. J. F. van; Buuren, Henk R. van; Berge‐Henegouwen, G. P. Van; Kate, Fiebo J.W. ten; Hop, Wim C. J.; Hoek, Egbert W. van der; Kerbert, Marjo J.; Lijf, Hans H. van; Ouden, Janny W. den; Smit, Adelbert M.; Vries, Richard A. de; Zanten, R.A.A. van; Schalm, Solko W.

doi:10.1016/s0168-8278(98)80254-7

Cited by 82 publications

(32 citation statements)

References 33 publications

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“…Some investigators believe that the most efficacious therapy for primary biliary cirrhosis involves a combination of an immunosupressive agent such as prednisone and UDCA 44 or the triple combination of UDCA, prednisone, and azathioprine. 45 Ursodeoxycholic acid therapy has also shown favorable effects in other cholestatic conditions, such as cholestasis associated with pregnancy 46 and cholestasis associated with total parenteral nutrition. 47 Other conditions in which the efficacy of UDCA therapy is being explored are reviewed by Beuers et al 39 Ursodeoxycholic acid was recently approved by the Food and Drug Administration for the treatment of primary biliary cirrhosis.…”

Section: Displacement Therapymentioning

confidence: 99%

The Continuing Importance of Bile Acids in Liver and Intestinal Disease

1999

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Bile acids, the water-soluble, amphipathic end products of cholesterol metabolism, are involved in liver, biliary, and intestinal disease. Formed in the liver, bile acids are absorbed actively from the small intestine, with each molecule undergoing multiple enterohepatic circulations before being excreted. After their synthesis from cholesterol, bile acids are conjugated with glycine or taurine, a process that makes them impermeable to cell membranes and permits high concentrations to persist in bile and intestinal content. The relation between the chemical structure and the multiple physiological functions of bile acids is reviewed. Bile acids induce biliary lipid secretion and solubilize cholesterol in bile, promoting its elimination. In the small intestine, bile acids solubilize dietary lipids promoting their absorption. Bile acids are cytotoxic when present in abnormally high concentrations. This may occur intracellularly, as occurs in the hepatocyte in cholestasis, or extracellularly, as occurs in the colon in patients with bile acid malabsorption. Disturbances in bile acid metabolism can be caused by (1) defective biosynthesis from cholesterol or defective conjugation, (2) defective membrane transport in the hepatocyte or ileal enterocyte, (3) defective transport between organs or biliary diversion, and (4) increased bacterial degradation during enterohepatic cycling. Bile acid therapy involves bile acid replacement in deficiency states or bile acid displacement by ursodeoxycholic acid, a noncytotoxic bile acid. In cholestatic liver disease, administration of ursodeoxycholic acid decreases hepatocyte injury by retained bile acids, improving liver tests, and slowing disease progression. Bile acid malabsorption may lead to high concentrations of bile acids in the colon and impaired colonic mucosal function; bile acid sequestrants provide symptomatic benefit for diarrhea. A knowledge of bile acid physiology and the perturbations of bile acid metabolism in liver and digestive disease should be useful for the internist.

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Section: Displacement Therapymentioning

confidence: 99%

The Continuing Importance of Bile Acids in Liver and Intestinal Disease

1999

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“…The largest (n = 265) randomized controlled trial (methotrexate/UDCA versus UDCA alone) did not find any significant differences in the rates of transplantation, transplantation-free survival, development of hepatic decompensation, biochemical deterioration or histological progression over a median study time of 7.6 years [Combes et al 2005]. Azathioprine has very little effect on improving serum liver biochemistry or hepatic histology in PBC [Heathcote et al 1976;Wolfhagen et al 1998] and although early trials suggested a tendency toward improved survival [Christensen et al 1985], this failed to reach statistical significance. Randomized trials have shown that cyclosporine had some effect on slowing biochemical and histological progression [Wiesner et al 1990;Lombard et al 1993].…”

Section: Fibric Acid Derivatesmentioning

confidence: 99%

Treatment of autoimmune liver disease: current and future therapeutic options

Trivedi

Hirschfield

2013

Therapeutic Advances in Chronic Disease

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Autoimmune liver disease spans three predominant processes, from the interface hepatitis of autoimmune hepatitis to the lymphocytic cholangitis of primary biliary cirrhosis, and finally the obstructive fibrosing sclerotic cholangiopathy of primary sclerosing cholangitis. Although all autoimmune in origin, they differ in their epidemiology, presentation and response to immunosuppressive therapy and bile acid based treatments. With an ongoing better appreciation of disease aetiology and pathogenesis, treatment is set ultimately to become more rational. We provide an overview of current and future therapies for patients with autoimmune liver disease, with an emphasis placed on some of the evidence that drives current practice.

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“…The use of corticosteroids to suppress the inflammation in PBC has been always considered as a very attractive approach [6,7,8,9]; however, their use can cause serious side effects, especially aggravating osteopenia. Budesonide, a nonhalogenated glucocorticoid with a high first-pass hepatic metabolism and a high affinity for the glucocorticoid receptor, exerts fewer side effects than conventional corticosteroids in patients with inflammatory bowel disease [10] or autoimmune hepatitis [11].…”

Section: Udca and Budesonide For Patients With Features Of Severe Pbcmentioning

confidence: 99%

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

Poupon¹

2011

Dig Dis

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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.

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Triple therapy with ursodeoxycholic acid, prednisone and azathioprine in primary biliary cirrhosis: a 1-year randomized, placebo-controlled study

Cited by 82 publications

References 33 publications

The Continuing Importance of Bile Acids in Liver and Intestinal Disease

The Continuing Importance of Bile Acids in Liver and Intestinal Disease

Treatment of autoimmune liver disease: current and future therapeutic options

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

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