S1881 The Therapeutic Efficacy of Ursodeoxycholic Acid (UDCA) in Drug-Induced Liver Injury: Results of a Randomized Controlled Trial

Abstract

Background: Drug-induced liver injury (DILI) is the leading cause of acute liver injury in many countries. There is no specific pharmacological treatment for this disease. Ursodeoxycholic acid (UDCA) is a hydrophilic bile acid that is increasingly used for the treatment of various cholestatic disorders. But there has been no clinical trial of UDCA in DILI to date. We aimed to evaluate the therapeutic benefit of UDCA in DILI based on a randomized controlled trial. Methods: Inor out-patients with DILI from our hospital were enrolled into this study under written consent. The diagnosis of DILI was according to the recommendation of the US drug-Induced Liver Injury Network (DILIN). Patients were randomized to treatment group (with UDCA 13-15 mg/day, divided into 3 doses) or placebo-controlled group. Liver biochemical tests and clinical symptoms and signs were assayed at least every 2 weeks. The outcome endpoint was DILI-related fatality, liver transplantation, or severe grade (serum total bilirubin ≧ 2.5 mg/dL, combined with international normalized ratio ≧ 1.5, ascites or encephalopathy) as the definition of DILIN. Results: A total of 112 patients were recruited (54 in the treatment group and 58 in the control group). There was no statistical difference of age, gender and percentage of type of DILI (hepatocellular, mixed, and cholestatic) between 2 groups. During the follow-up, there was no statistical discrepancy of serial serum alanine aminotransferase, aspartate aminotransferase and total bilirubin between 2 groups. During treatment, serial serum alkaline phosphatase levels in the treatment group were lower than those in the control group (p = 0.039, repeated measures two-way ANOVA). Nine (16.6%) of the 54 patients in the treatment group, and 10 (17.2%) of the 58 patients in the control group had met the outcome endpoint, which revealed no statistical difference (p = 0.907, Log rank test). Age was the risk factor to have this unfavorable outcome by Cox regression test (Hazard Ratio = 1.064, 95% CI = 1.025-1.104, p = 0.001). Conclusion: Although UDCA may have the therapeutic effect in lowering serum alkaline phosphatase in patients with DILI, it has no clinical benefit in terms of decreasing mortality and severe DILI. Further studies with higher dose of UDCA and larger sample size are mandatory, based on the therapeutic potential of UDCA shown in this study.