Gastroenterology

Gastroenterology

Volume 138, Issue 5, May 2010, Pages 1755-1762.e2
Gastroenterology

Clinical—Liver, Pancreas, and Biliary Tract
Pentoxifylline Does Not Decrease Short-term Mortality but Does Reduce Complications in Patients With Advanced Cirrhosis

https://doi.org/10.1053/j.gastro.2010.01.040Get rights and content

Background & Aims

Pentoxifylline, an inhibitor of tumor necrosis factor-α, is given to patients with liver diseases, but its effects in patients with advanced cirrhosis are unknown. We performed a randomized, placebo-controlled, double-blind trial of its effects in patients with cirrhosis.

Methods

A total of 335 patients with cirrhosis (Child–Pugh class C) were assigned to groups given either pentoxifylline (400 mg, orally, 3 times daily; n = 164) or placebo (n = 171) for 6 months. The primary end point was mortality at 2 months. Secondary end points were mortality at 6 months and development of liver-related complications.

Results

By 2 months, 28 patients in the pentoxifylline group (16.5%) and 31 in the placebo group (18.2%) had died (P = .84). At 6 months, 50 patients in the pentoxifylline group (30.0%) and 54 in the placebo group (31.5%) had died (P = .75). The proportions of patients without complications (eg, bacterial infection, renal insufficiency, hepatic encephalopathy, or gastrointestinal hemorrhage) were higher in the pentoxifylline group than in the placebo group at 2 months (78.6% vs 63.4%; P = .006) and 6 months (66.8% vs 49.7%; P = .002). The probability of survival without complications was higher in the pentoxifylline group than in the placebo group at 2 and 6 months (P = .04). In multivariate analysis, the factors associated with death were age, the Model for End-Stage Liver Disease score, and presence of early-stage carcinoma. Treatment with pentoxifylline was the only factor associated with liver-related complications.

Conclusions

Although pentoxifylline does not decrease short-term mortality in patients with advanced cirrhosis, it does reduce the risk of complications.

Section snippets

Materials and Methods

The study was an investigator-initiated, randomized, double-blind, placebo-controlled, clinical trial conducted in 9 sites. The protocol was approved by the ethics committee (CCPPRB of Bichat-Claude-Bernard Paris, France) and all patients gave written informed consent. Although pentoxifylline and placebo were purchased from Sanofi-Aventis, Sanofi-Aventis did not participate in any part of the study, including study design, data analysis, and manuscript preparation.

Results

A total of 342 patients underwent randomization. Seven patients dropped out; these patients did not take any tablets and were excluded from analysis (Supplementary Figure 1). Of the remaining 335 patients, 164 received pentoxifylline and 171 received placebo. Three patients in the pentoxifylline group were lost to follow-up (2 at 1 month and 1 at 2 months) and 3 in the placebo group (1 at 2 months, 1 at 3 months and 1 at 5 months).

Mean duration of treatment in the pentoxifylline group was 149

Discussion

In this trial, pentoxifylline was prescribed in patients with cirrhosis and liver failure to reduce mortality by 50% and decrease development of liver-related complications. The indication for pentoxifylline in these patients is based on different reasons. Proinflammatory cytokine production is increased in these patients and has deleterious effects on the liver and other organs.1, 2 Pentoxifylline administration has been found to affect numerous steps in the cytokine inflammatory pathway,

Acknowledgments

We are indebted to C. Quintin and S. Bougouin (Unite de Recherche Clinique Paris Nord) for their efforts in the implementation and monitoring of the study. We also thank Drs S. Djane, A. Tibi, and F. Tubach for their help. RM is in receipt of an Interface INSERM-AP-HP fellowship.

ClinicalTrials.gov number, NCT00162552.

References (37)

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Conflicts of interest The authors disclose no conflicts.

Funding Supported by a grant from the French Ministry of Health. The sponsor was the Département de la Recherche Clinique et du Développement, Assistance Publique-Hôpitaux de Paris (PHRC AOM03120).

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