Oral budesonide and ursodeoxycholic acid for treatment of primary biliary cirrhosis: results of a prospective double-blind trial.
ABSTRACT Ursodeoxycholic acid (UDCA) is used for treatment of primary biliary cirrhosis. Previous studies showed that, compared with UDCA monotherapy, bile salts plus prednisolone had no further effect on laboratory data but improved liver histology. Thirty percent of these patients had prednisolone-related side effects. Budesonide is a glucocorticoid with a high receptor affinity and a high first-pass metabolism. In this study we investigated whether budesonide and UDCA are superior to UDCA monotherapy.
A 2-year prospective, controlled double-blind trial was performed. Twenty patients (mainly with early-stage disease) were treated with UDCA at a dose of 10-15 mg/kg daily in addition to 3 mg budesonide 3 times daily (group A), and 19 patients (1 dropped out for personal reasons) were treated with UDCA plus placebo (group B). Liver biopsy specimens were taken before, after 12 months, and at the end of study. Glucose tolerance tests, serum cortisol levels, and adrenocorticotropin-stimulated cortisol secretion were assessed at regular intervals. Bone mass density was measured by dual-energy photon absorptiometry.
Compared with pretreatment values, liver enzyme and immunoglobulin M and G levels decreased significantly in both groups. Improvement in group A was significantly more pronounced (P < 0.05) than in group B. Titers of antimitochondrial antibodies did not change. In group A, the point score of liver histology improved by 30.3%; in group B, it deteriorated by 3.5% (P < 0.001). Changes in bone mineral density after 2 years were -1.747% in group A and -0.983% in group B (P = 0.43). Budesonide had little influence on the hypothalamic-pituitary-adrenal axis. One patient in group A had budesonide-related side effects; in 3 patients in group B, complications of liver disease developed.
Combination therapy with UDCA and budesonide is superior to UDCA and placebo.
Article: Treatment of primary biliary cirrhosis: therapy with choleretic and immunosuppressive agents.[show abstract] [hide abstract]
ABSTRACT: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of presumed autoimmune etiology affecting predominantly middle-aged women; it is a slowly progressive disease causing loss of intrahepatic bile ducts, resulting in advanced fibrosis, cirrhosis, and liver failure. Many drugs have been studied for treatment, including agents with choleretic and immunosuppressive properties. Ursodeoxycholic acid (UDCA) has been evaluated most widely. After liver failure, the only effective treatment is liver transplantation. Effective therapy reduces the need for transplantation and improves life expectancy. For advanced liver disease or incomplete response to UDCA, new therapies to cure or retard the progression of disease in PBC are needed.Clinics in Liver Disease 06/2008; 12(2):425-43; x-xi. · 3.18 Impact Factor
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ABSTRACT: Exposure to cholestatic injury (e.g., drugs, hormones, proinflammatory cytokines, biliary obstruction/destruction), hereditary mutations of transporter genes, or the combination of both result in decreased expression and function of hepatobiliary transport systems. These molecular changes may contribute to impaired hepatic uptake and excretion of bile salts and other organic anions (e.g., bilirubin) in cholestasis. In addition, alterations in transporter expression may represent secondary and adaptive changes, limiting the accumulation of potentially toxic biliary constituents in the cholestatic liver by providing alternative excretory routes. The mediators and molecular mechanisms responsible for changes in transporter expression are being increasingly understood at transcriptional and post-transcriptional levels. The molecular changes of hepatobiliary transport systems in cholestasis may represent a potential target for specific therapeutic interventions aimed at restoration of defective hepatobilary transporter expression and stimulation of adaptive rescue pathways.02/2011: pages 266-288;
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ABSTRACT: In most cholestatic liver diseases the cause of the disease is not known and therapy can only be directed toward suppression of the pathogenetic processes and amelioration of the consequences of cholestasis. The recognition of adaptive-compensatory responses to cholestasis has become of major importance. They tend to minimize retention of bile acids and other potentially toxic solutes in the hepatocyte by limiting hepatocellular uptake, reducing bile acid synthesis, stimulating detoxification, and up-regulating alternative pathways for excretion. Some of the drugs used for the treatment of cholestatic liver diseases in an empiric way turned out to be modulators of nuclear receptors, which regulate these adaptive-compensatory responses. New drugs are being designed and tested along these lines and may be regarded as treatment opportunities of the future.Clinics in Liver Disease 03/2008; 12(1):53-80, viii. · 3.18 Impact Factor