Pentoxifylline does not decrease short-term mortality but does reduce complications in patients with advanced cirrhosis.
OBJECTIVE
Pentoxifylline, an inhibitor of tumor necrosis factor-alpha, 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.
Lebrec
Didier
D
INSERM, Unité 773, Centre de Recherche Biomédicle Bichat-Beaujon CRB3, Paris, France and Service d'Hépatologie, Hôpital Beaujon, Clichy, France. didier.lebrec@inserm.fr
Thabut
Dominique
D
Oberti
Frederic
F
Perarnau
Jean-Marc
JM
Condat
Bertrand
B
Barraud
Helene
H
Saliba
Faouzi
F
Carbonell
Nicolas
N
Renard
Philippe
P
Ramond
Marie-Jose
MJ
Moreau
Richard
R
Poynard
Thierry
T
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001424:Bacterial Infections / Q000209:etiology / Q000517:prevention & control; D004311:Double-Blind Method; D005602:France / Q000453:epidemiology; D006471:Gastrointestinal Hemorrhage / Q000209:etiology / Q000517:prevention & control; D006501:Hepatic Encephalopathy / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D008875:Middle Aged; D010431:Pentoxifylline / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D051437:Renal Insufficiency / Q000209:etiology / Q000517:prevention & control; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D014409:Tumor Necrosis Factor-alpha; D010431:Pentoxifylline