Clinical—Liver, Pancreas, and Biliary TractPentoxifylline Does Not Decrease Short-term Mortality but Does Reduce Complications in Patients With Advanced Cirrhosis
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)
- et al.
Cytokines and the liver
J Hepatol
(1997) - et al.
Serum levels of cytokines in chronic liver diseases
Gastroenterology
(1992) - et al.
Bacterial infection in the pathogenesis of variceal bleeding
Lancet
(1999) - et al.
Tumor necrosis factor alpha and interleukin-6 plasma levels in infected cirrhotic patients
Gastroenterology
(1993) - et al.
Upregulation of TNF-alpha production signalling pathways in monocytes from patients with advanced cirrhosis: possible role of Akt and IRAK-M
J Hepatol
(2006) - et al.
In vivo altered unfolded protein response and apoptosis in livers from lipopolysaccharide-challenged cirrhotic rats
J Hepatol
(2007) - et al.
Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: a double-blind, placebo-controlled trial
Gastroenterology
(2000) - et al.
Assessment of the prognosis of cirrhosis: Child-Pugh versus MELD
J Hepatol
(2005) - et al.
In vitro effect of platelet-derived growth factor on fibroproliferation and effect on cytokine antagonists
Immunopharmacology
(1994) Pentoxifylline inhibits ICAM-1 expression and chemokine production induced by proinflammatory cytokines in human pulmonary epithelial cells
Immunopharmacology
(2000)
Norfloxacin reduces aortic NO synthases and proinflammatory cytokine up-regulation in cirrhotic rats: role of Akt signalling
Gastroenterology
Molecular determinants of crosstalk between nuclear receptors and toll-like receptors
Cell
Short-term prognosis in critically ill patients with cirrhosis assessed by prognostic scoring systems
Hepatology
A model to predict survival in patients with end-stage liver disease
Hepatology
Soluble TNF-R1, but not tumor necrosis factor alpha, predicts the 3-month mortality in patients with alcoholic hepatitis
J Hepatol
A randomized, double-blinded, placebo-controlled multicenter trial of etanercept in the treatment of alcoholic hepatitis
Gastroenterology
Pentoxifylline prevents small intestinal bacterial overgrowth, bacterial translocation, and spontaneous bacterial peritonitis in experimental cirrhosis
J Hepatol
Cytokines: overview
Semin Liver Dis
Cited by (0)
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).