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Prednisolone with vs. without Pentoxifylline and Survival of Patients with Severe Alcoholic Hepatitis: a Randomized Clinical Trial
Prednisolone with vs. without Pentoxifylline and Survival of Patients with Severe Alcoholic Hepatitis: A Randomized Clinical Trial. Mathurin P, Louvet A, Duhamel A, et al. JAMA. 2013;310:1033-41.
Study Question: Does the combination of prednisolone and pentoxifylline improve 6-month survival compared to prednisolone alone?
Study Description: This study was a multicenter, randomized, double-blind trial conducted between December 2007 and March 2010. Patients received either a combination of prednisolone 40 mg once daily and pentoxifylline 400 mg three times daily for 28 days or prednisolone 40 mg once daily and placebo for 28 days. Patients were included if they were 18-70 years old, heavy drinkers, and had severe biopsy-proven alcoholic hepatitis as indicated by recent onset of jaundice within the past 3 months and a Maddrey score of at least 32 (indicating severe disease). The primary outcome was survival at 6 months.
Results: A total of 270 patients were included in the intention-to-treat analysis (pentoxifylline-prednisolone, n = 133; placebo-prednisolone, n = 137). At the 6-month follow-up, 40 patients in the pentoxifylline-prednisolone group and 42 patients in the prednisolone group (69.9% [95% CI, 62.1%-77.7%] vs. 69.2% [95% CI, 61.4%-76.9%], p = 0.91) died. The Lille score (HR, 12.55; 95% CI, 5.19-30.34) and the Model for End-Stage Liver Disease score (HR, 1.11; 95% CI, 1.03-1.19) were independently associated with 6-month survival. At 7 days, treatment response to therapy was not significantly different between the groups as assessed by the Lille model (Lille model score, 0.41 [95% CI, 0.36-0.46] vs. 0.40 [95% CI, 0.35-0.45], p = 0.80). At one month, the pentoxifylline-prednisolone group had a lower incidence of hepatorenal syndrome, but this difference was not achieve statistical significance at 6 months (8.4% [95% CI, 4.8%-14.8%] vs. 15.3% [95% CI, 10.3%-22.7%], p = 0.07).
Conclusion(s): The addition of pentoxifylline to prednisolone did not improve survival compared to prednisolone alone. This study does not support the use of combination therapy for treatment of severe alcoholic hepatitis.
Perspective: Although the study was powered to demonstrate that combination therapy did not affect 6-month survival, the study was not powered to detect differences in rates of hepatorenal syndrome.