Corticosteroid Plus Pentoxifylline Is Not Better than Corticosteroid Alone for Improving Survival in Severe Alcoholic Hepatitis (COPE Trial)

Corticosteroids and pentoxifylline reduce short-term mortality in severe alcoholic hepatitis (SAH), but not to the extent desired. Combining both drugs may lead to better survival, but has not yet been studied. To compare the efficacy of corticosteroids plus pentoxifylline with that of corticosteroids alone in improving survival of SAH patients. Of the 111 patients screened, 70 patients with SAH (Maddrey discriminant function (MDF) a parts per thousand yen 32) were enrolled. Patients with active infection, bleeding, renal failure, or pancreatitis were excluded. Treatment was given for four weeks to group A (n = 36; prednisolone 40 mg/day plus pentoxifylline 400 mg thrice/day) and group B (n = 34; prednisolone 40 mg/day). Patients were followed up for 6 months. Data are expressed as median (range) or percentage. Baseline characteristics of the two groups were similar (MDF group A 78.5 (36.8-140.9), group B 74.9 (45.6-140.2)). Four-week and six-month survival in groups A and B were not significantly different (four-week 72.2 and 73.5%, respectively, p = 1.00; six-month 30.6 and 23.5%, respectively, p = 0.417). At seven days, 55.6% of patients in group A and 64.7% in group B had a Lille score < 0.45 (p = 0.473). Six-month survival was significantly higher for patients with a Lille Score < 0.45 than for those with a Lille score a parts per thousand yen0.45 (group A 55.5 vs. 0%, p = 0.0006; group B 36 vs. 0%, p = 0.0304). Biological improvement at 28 days was significant for both groups; however, the difference between the groups was not significant. For patients with severe alcoholic hepatitis, a combination of corticosteroids and pentoxifylline has no additional survival advantage compared with corticosteroids alone.