The clinical effectiveness and cost-effectiveness of STeroids or Pentoxifylline for Alcoholic Hepatitis (STOPAH): a 2x2 factorial, randomised controlled trial

In the UK, the mortality rate from alcoholic liver disease is rising rapidly, and so STOPAH is considered as a vitally important study, being more than 10x larger than any previous study in this patient population. Since 1971 there have been 13 randomised studies and 4 meta-analyses investigating the role of corticosteroid therapy for this condition. Despite this apparent wealth of evidence, controversy persists and there remains deep division with regard to the use of corticosteroids Pentoxifylline (PTX) has also recently been studied in the treatment of alcoholic hepatitis. It is believed to act, in part, by inhibiting the synthesis of the pro-inflammatory cytokine tumour necrosis factor alpha. There has been one randomised controlled trial which showed significant benefit. On review of the published studies, none of these reach an adequate statistical power to make a statement with 80% confidence. The two most recent meta-analyses of all of the available trials demonstrated that although there was a trend of benefit with steroids, the results were either not statistically significant or impossible to interpret due to the heterogeneity of the incorporated studies. However, a re-analysis of the 3 largest studies indicated a significant benefit from corticosteroid. In this meta-analysis, patients with a discriminant function (DF) greater than or equal to 32, treated with prednisolone, had 28 day mortality of 15%, as opposed to a mortality of 35% amongst placebo-treated patients (p=0.001). Only one study has demonstrated the benefit of pentoxifylline (PTX) in alcoholic hepatitis. No study has compared the effects of prednisolone and PTX directly, nor has any study compared the combination of these treatments with corticosteroid monotherapy.