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Prednisolone with vs without pentoxifylline and survival of patients with severe alcoholic hepatitis: A randomized clinical trial

Philippe Mathurin 1 Alexandre Louvet 2, 3 Alain Duhamel 4 Pierre Nahon 5 Nicolas Carbonell 6 Jérôme Boursier 7 Rodolphe Anty 8, 9 Emmanuel Diaz Dominique Thabut 10 Romain Moirand 11 Didier Leberc Christophe Moreno 12 Nathalie Talbodec 13 Thierry Paupard 14 Sylvie Naveau 15, 16, 17 Christine Silvain 18, 19 Georges-Philippe Pageaux 20 Rodolphe Sobesky 21, 22, 23, 24 Valérie Canva-Delcambre 25 Sébastien Dharancy 26 Julia Salleron 27 Thong Dao 28
Abstract :

Importance  Prednisolone or pentoxifylline is recommended for severe alcoholic hepatitis, a life-threatening disease. The benefit of their combination is unknown.

Objective  To determine whether the addition of pentoxifylline to prednisolone is more effective than prednisolone alone.

Design, Setting, and Participants  Multicenter, randomized, double-blind clinical trial conducted between December 2007 and March 2010 in 1 Belgian and 23 French hospitals of 270 patients aged 18 to 70 years who were heavy drinkers with severe biopsy-proven alcoholic hepatitis, as indicated by recent onset of jaundice in the prior 3 months and a Maddrey score of at least 32. Duration of follow-up was 6 months. The last included patient completed the study in October 2010. None of the patients were lost to follow-up for the main outcome.

Intervention  Patients were randomly assigned to receive either a combination of 40 mg of prednisolone once a day and 400 mg of pentoxifylline 3 times a day (n=133) for 28 days, or 40 mg of prednisolone and matching placebo (n=137) for 28 days.

Main Outcomes and Measures  Six-month survival, with secondary end points of development of hepatorenal syndrome and response to therapy based on the Lille model, which defines treatment nonresponders after 7 days of initiation of treatment.

Results  In intention-to-treat analysis, 6-month survival was not different in the pentoxifylline-prednisolone and placebo-prednisolone groups (69.9% [95% CI, 62.1%-77.7%] vs 69.2% [95% CI; 61.4%-76.9%], P = .91), corresponding to 40 vs 42 deaths, respectively. In multivariable analysis, only the Lille model and the Model for End-Stage Liver Disease score were independently associated with 6-month survival. At 7 days, response to therapy assessed by the Lille model was not significantly different between the 2 groups (Lille model score, 0.41 [95% CI, 0.36-0.46] vs 0.40 [95% CI, 0.35-0.45], P = .80). The probability of being a responder was not different in both groups (62.6% [95% CI, 53.9%-71.3%] vs 61.9% [95% CI, 53.7%-70.3%], P = .91). The cumulative incidence of hepatorenal syndrome at 6 months was not significantly different in the pentoxifylline-prednisolone and the placebo-prednisolone groups (8.4% [95% CI, 4.8%-14.8%] vs 15.3% [95% CI, 10.3%-22.7%], P = .07).

Conclusion and Relevance  In patients with alcoholic hepatitis, 4-week treatment with pentoxifylline and prednisolone, compared with prednisolone alone, did not result in improved 6-month survival. The study may have been underpowered to detect a significant difference in incidence of hepatorenal syndrome, which was less frequent in the group receiving pentoxifylline.

Trial Registration Identifier: NCT01214226.

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Soumis le : mercredi 23 juin 2021 - 14:21:15
Dernière modification le : samedi 21 mai 2022 - 03:22:15

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Philippe Mathurin, Alexandre Louvet, Alain Duhamel, Pierre Nahon, Nicolas Carbonell, et al.. Prednisolone with vs without pentoxifylline and survival of patients with severe alcoholic hepatitis: A randomized clinical trial. Journal of the American Medical Association, American Medical Association (AMA), 2013, 310 (10), pp.1033-1041. ⟨10.1001/jama.2013.276300⟩. ⟨hal-03268756⟩



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