Controlled trial of methylprednisolone therapy in severe acute alcoholic hepatitis.

Abstract

SUMMARY The efficacy of methylprednisolone (1 g daily for three days), which is effective in reversing transplant rejection, was assessed in a randomised controlled trial of 55 patients with severe acute alcoholic hepatitis, 34 of whom had encephalopathy. The clinical progress, frequency of bleeding and sepsis, and cause of death were similar in the treatment (27 patients) and control groups (28 patients). There was no significant difference in mortality rgte between the two groups: 57% of the control group and 63% of the treatment group died during the study. Patients' survival depended on the presence or absence of the following features: encephalopathy, serum bilirubin concentration more than 340 Mmol/l, serum creatinine concentration more than 250 umol/l, and histological evidence of cirrhosis as well as severe acute alcoholic hepatitis.In addition to the direct toxic effects of alcohol, immunological mechanisms may also be involved in the pathogenesis of acute alcoholic hepatitis.' -3 Thus patients are sometimes treated with corticosteroids, although the efficacy of this approach remains uncertain. Of a total of nine studies4 -12 only three4 9 11 have shown a significant improvement in survival with corticosteriods. One of the factors responsible for the conflicting results of these previous studies may be related to the wide range in severity of alcoholic hepatitis. Therefore in this study we have included only the most severely ill patients. In previous trials only standard doses of prednisolone (up to 100 mg/day or its equivalent corticosteroid) were given, usually for a four to six week period. Apart from their anti-inflammatory effects, corticosteroids, at least in high doses, also inhibit T cell function and, as cellular immune responses to autologous and homologous liver antigens have been found in alcoholic hepatitis,'3 we have prescribed large doses of methylprednisolone for three days only, a regimen which is effective in reversing acute (cell-mediated) rejection of renal transplants. 14 Methods PATIENTSSixty patients who had been referred from other

Early Liver Transplantation for Severe Alcoholic Hepatitis in the United States—A Single-Center Experience

“…Nonresponders to medical therapy for severe AH experienced a dismal 6-month mortality rate of 70%, comparable to that of previous studies (27)(28)(29)(30). The high proportion of nonresponders was likely due to referral bias, as more than two-thirds of this cohort was composed of interhospital transfers, which increased over time for early LT consideration and highlights the key role of local providers.…”

Prevalence of Septic Events, Type 1 Hepatorenal Syndrome, and Mortality in Severe Alcoholic Hepatitis and Utility of Discriminant Function and MELD Score in Predicting These Adverse Events

“…Proponents of steroids argue that none of the steroid trials have shown increased morbidity or mortality from sepsis in patients with AH. This, however, may have been because of the short followup [6,[8][9][10][11]. A Spanish study that compared enteral nutrition with steroids in severe AH observed similar short-term outcomes in both groups, but reported significantly higher 1-year mortality (largely from sepsis) in the group given steroids (33% versus 4%) [25].…”

“…Although studies have addressed the prevalence and outcome of SE and type 1 HRS in patients with cirrhosis, there are no similar studies in those with advanced AH. Furthermore, although DF has been shown to predict mortality in AH [6][7][8][9][10][11], the utility of the MELD score has not been extensively studied in this regard. The aims of this study were therefore to assess the (a) prevalence of SE, type 1 HRS, and short-term mortality in patients with severe AH compared to those with advanced cirrhosis in absence of AH, and (b) predictors of these adverse events in patients with AH with special reference to the DF and the MELD score…”

“…Its clinical severity is assessed by discriminant function (DF) and those with a DF of ≥32 at presentation have a 50% in-hospital mortality rate [6][7][8][9][10][11]. Drug therapy of AH remains controversial, with some advocating steroids, and others, tumor necrosis factor (TNF) inhibitors like pentoxifylline.…”

Alcoholic hepatitis: The pivotal role of Kupffer cells

“…However severe AH carries a high mortality rate: 35% at 28 d without effective treatment [63] . These high mor- [99] PRED vs placebo Randomized control No difference in mortality Ramond et al [100] PRED vs placebo Double-blinded, randomized control Improved mortality with PRED Akriviadis et al [69] PTX vs placebo Double-blinded, randomized control Improved mortality with PTX Sidhu et al [101] PTX vs placebo Randomized control Improved mortality with PTX De et al [102] PTX vs PRED Double-blinded, randomized control Reduced mortality with PTX Park et al [103] PTX vs PRED Randomized control Reduced mortality with PRED Mathurin et al [104] PRED vs PRED + PTX Multicenter, double-blinded, randomized control No difference in mortality De et al [105] PTX vs PTX + PRED Double-blinded, randomized control No difference in mortality Thursz et al [70] PTX vs PRED vs placebo Multicenter, double-blinded, randomized control No difference in mortality N-acetylcysteine Moreno et al [106] NAC vs placebo Multicenter, single-blinded, randomized control No difference in mortality Cytokine inhibitors Naveau et al [72] Infliximab vs placebo Double-blinded, randomized control Increased mortality with infliximab Boetticher et al [71] Etancercept vs placebo Multicenter, single-blinded, randomized control Increased mortality with etancercept PTX: Pentoxifylline; PRED: Prednisiolone; NAC: N-acetylcysteine.…”