Effects of long-term rifampicin administration in primary biliary cirrhosis. Gastroenterology

Liver Unit, Hospital Clínic i Provincial, University of Barcelona, Spain.
Gastroenterology (Impact Factor: 16.72). 07/1992; 102(6):2077-80. DOI: 10.1016/0168-8278(89)90386-3
Source: PubMed


The effects of rifampicin treatment (10 on pruritus and cholestasis were evaluated in 16 patients with primary biliary cirrhosis and pruritus followed up for 2-24 months. Assessment of pruritus severity, liver tests, aminopyrine breath test, and bile acids was done at 2 weeks and every 3 months after the beginning of the study. Two patients (12.5%) were withdrawn after 2 months of treatment because they had hepatitis caused by rifampicin. Four patients were withdrawn after 4 months because of liver transplantation (3 cases) and the development of leg edema associated with administration of rifampicin. The remaining 10 patients received therapy for 14.4 +/- 0.7 months and did not experience side effects. Pruritus improved in all patients and disappeared in 11 patients (79%) after 3 months of treatment. Moreover, all patients followed up for more than 1 year were free of pruritus. The alkaline phosphatase level decreased significantly, and the aminopyrine breath test results increased significantly after 2 weeks of treatment (P less than 0.001) and did not change thereafter. In the 9 patients treated for 15 months, alkaline phosphatase levels decreased to 63% of the basal levels and aminopyrine breath test results increased to 153% of baseline values. Transaminases, gamma-glutamyltransferase, and total bile salt levels decreased significantly after 2 weeks of treatment but returned to baseline after 3 months. No changes in bilirubin and cholesterol levels were observed. It is concluded that long-term rifampicin treatment is effective for relieving pruritus in primary biliary cirrhosis, but liver enzymes should be monitored to detect drug-induced hepatitis.

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    • "Various prospective randomized, placebo-controlled trials have proven that rifampicin at doses of 300—600 mg/d [56] [126] [127] and 10 mg/kg per day [57], respectively, is an effective and safe treatment of cholestatic pruritus . Hepatotoxicity, after treatment for several weeks or months, may be an adverse effect of rifampicin in up to 12% of cholestatic patients [57], requiring the monitoring of serum transaminase levels at regular intervals [128]. If rifampicin is ineffective, the ␮-opoid antagonist naltrexone should be regarded as third line therapy. "
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    • "A range of additional nuclear (e.g., PXR, CAR and PPARa) and bile acid (e.g., TGR5) receptor agonists, which impact on detoxification and alternative export mechanisms, bile composition, fibrosis and inflammatory responses are currently under investigation with promising results in animal models of cholestasis. Some drugs such as rifampicin and phenobarbital have been used in the pre-UDCA area for the treatment of cholestatic pruritus and jaundice and later turned out to be activators of PXR and CAR, respectively [185] [186]. Also agonists of peroxisome proliferator-activated receptor alpha (PPARa, NR1C1) are promising therapeutic approaches in human cholestatic liver disease since fibrates showed beneficial effects on biochemical parameters of cholestasis and/or transaminases in PBC patients with suboptimal response to UDCA [187] [188] [189]. "
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