Systematic review: glucocorticosteroids for alcoholic hepatitis – a Cochrane Hepato‐Biliary Group systematic review with meta‐analyses and trial sequential analyses of randomized clinical trials

Abstract

SUMMARY BackgroundGlucocorticosteroids versus placebo or no intervention for patients with alcoholic hepatitis have been evaluated for more than 35 years. However, the results of randomized trials and meta-analyses differ substantially.

Pharmacologic Treatment of Alcoholic Hepatitis: Examining Outcomes Based on Disease Severity Stratification

“…While meta-analysis of several older, small trials of steroid therapy have shown short-term mortality benefit, its utilization remains controversial due to concern for infection development and the emergence of new literature challenging previous findings. 5,6,11 Along the same accord, a recent meta-analysis of pentoxifylline demonstrated a decreased incidence of fatal HRS but no short-term survival benefit compared to placebo. 12 Lack of survival benefit was most recently described by Thursz and colleagues in the STOPAH trial, which evaluated the effects of prednisolone and pentoxifylline therapy in 1103 severe AH patients with higher average MDF scores in the treatment group compared to our study (MDF = 63 in STOPAH vs. MDF = 42 in our study).…”

“…One hypothesis that has been proposed to explain higher mortality rates in patients with more severe disease is a ceiling effect of drug therapy in preventing the inflammatory cascade and ultimate liver damage. 2,5 Mendenhall and colleagues first described this phenomenon after observing that steroid treatment increased mortality in patients with an MDF > 54. 5 This cutoff should be further studied to determine if a true MDF range of treatment benefit exists before reaching a treatment ceiling.…”

“…3,4evidence that corticosteroid treatment is primarily beneficial in severe AH patients. 5,6 While a 28-day duration of prednisolone 40 mg daily is regarded as the gold standard of therapy, it may not be ideal in patients with an active gastrointestinal (GI) bleed or infection due to risk of further exacerbation of these conditions. One alternative to corticosteroid therapy that has been studied is an oral phosphodiesterase inhibitor, pentoxifylline.…”

Role of Pentoxifylline and Steroids for Alcoholic Hepatitis – Has the last word been said?

“…The authors concluded that the current evidence does not support the use of steroids in AH and large low bias well designed RCTs are required. 7 Park et al 8 in a multicentre, open labelled noninferiority trial involving 124 patients with severe AH compared the short term mortality among the patients randomised to steroids or pentoxifylline. Patients were treated with either prednisolone 40 mg per day or pentoxifylline 1200 mg per day for 4 weeks.…”

Can we reliably predict response to corticosteroid treatment in severe alcoholic hepatitis?

“…However, the widespread utility of prednisolone, a corticosteroid with broad anti‐inflammatory and immunosuppressive actions, in improving survival outcomes in SAH remains controversial. From 1971 to 2014, there have been 13 randomized trials and four meta‐analyses that have investigated the use of corticosteroids in SAH 4, 5. In the main, these studies have indicated that steroids significantly increased the short‐term survival of patients with SAH, but concerns have revolved around the risk of sepsis and gastrointestinal hemorrhage.…”