EVIDENCE-BASED ANSWER
Pentoxifylline improves short-term survival in patients admitted to the hospital with severe alcoholic hepatitis (strength of recommendation [SOR]: B, a single published randomized controlled trial [RCT]). Pentoxifylline does not improve survival when it is substituted for steroids in hospitalized patients who aren’t responding to steroids (SOR: C, case series).
Evidence summary
Patients with severe acute alcoholic hepatitis have elevated levels of serum tumor necrosis factor (TNF), suggesting that TNF release may play a role in liver inflammation.1 Because pentoxifylline inhibits TNF synthesis, it has been evaluated as a potential therapy for alcoholic hepatitis.
Decreases in mortality and hepatorenal syndrome
In a hospital-based clinical trial, 101 patients admitted with severe alcoholic hepatitis (mean age 42 years, 74% men) were randomized to oral pentoxifylline 400 mg twice a day or placebo (vitamin B12 tablets) for 4 weeks.1 The main outcome measures were short-term survival and progression to hepatorenal syndrome. Severe alcoholic hepatitis was defined as a Maddrey discriminant factor (DF) >32, jaundice, and at least one of the following: tender hepatomegaly, fever, leukocytosis, hepatic encephalopathy, or hepatic systolic bruit. The DF is calculated as follows: 4.6 × [prothrombin time in seconds – control time] + bilirubin (mg/dL). Medical management was “individualized according to each patient’s condition.”
Pentoxifylline therapy was associated with decreased mortality during the index hospitalization (relative risk [RR]=0.59; 95% confidence interval [CI], 0.35-0.97; number needed to treat [NNT]=5). Hepatorenal syndrome also decreased (RR=0.29; 95% CI, 0.13-0.65; NNT=4). Patients in the pentoxifylline group tended to have more headaches and gastrointestinal side effects, but no other serious health hazards were observed.