Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: A double-blind, placebo-controlled trial

Background & Aims:An earlier pilot study from our river unit suggested bene fit from treatment with pentoxifylline (PTX), an inhibitor of tumor necrosi s factor (TNF), in severe acute alcoholic hepatitis. The aim of the present study was to evaluate this treatment in a larger cohort of patients. Metho ds: One hundred one patients with severe alcoholic hepatitis (Maddrey discr iminant factor greater than or equal to 32) entered a 4-week double-blind r andomized trial of PTX (400 mg orally 3 times daily) vs, placebo. Primary e ndpoints of the study were the effect of PTX on (1) short-term survival and (2) progression to hepatorenal syndrome. On randomization, there were no d ifferences in demographic and clinical characteristics or laboratory values (including TNF) between the 2 groups. Results: Twelve (24.5%) of the 49 pa tients who received PTX and 24 (46.1%) of the 52 patients who received plac ebo died during the index hospitalization (P = 0.037; relative risk, 0.59; 95% confidence interval, 0.35-0.97). Hepatorenal syndrome was the cause of death in 6 (50%) and 22 (91.7%) patients (P = 0.009; relative risk, 0.29; 9 5% confidence interval, 0.13-0.65). Three variables (age, creatinine level on randomization, and treatment with PTX) were independently associated wit h survival. TNF Values on randomization were not predictive of survival; ho wever, during the study period they increased markedly in nonsurvivors comp ared with survivors in both groups. Conclusions: Treatment with PTX improve s short-term survival in patients with severe alcoholic hepatitis. The bene fit appears to be related to a significant decrease in the risk of developi ng hepatorenal syndrome. increasing TNF levels during the hospital course a re associated with an increase in mortality rate.