S2480 Heterogeneity in Randomized Controlled Trials of Corticosteroid Use for Alcoholic Hepatitis: Implications for Efficacy and Infection Risk

Introduction: Corticosteroids are the mainstay treatment for severe alcoholic hepatitis (AH), yet randomized controlled trials (RCTs) report conflicting outcomes. A key contributor to this is heterogeneity in study design, including differences in steroid regimens, patient selection, infection surveillance, and follow-up. This systematic review evaluates RCTs of corticosteroids in AH to assess heterogeneity in study design and outcomes reporting. Methods: Twenty-nine RCTs evaluating corticosteroid therapy in AH were analyzed. Key variables included steroid regimen, tapering protocols, treatment duration, initiation timing, comparator arms, geographic setting, and infection outcomes. Infections were categorized as bacterial (B), fungal (F), viral (V), or not specified (NS), and reported at baseline and during follow-up. Studies were also classified by the presence and duration of follow-up protocols. Results: Trial designs showed substantial heterogeneity. Steroid regimens varied from prednisolone 40 mg daily to pulse methylprednisolone or tapered protocols. Tapering strategies ranged from none to 12-day, 2-week, or 4-week regimens. Timing of initiation spanned from <3 to >13 days post-admission. Comparators included placebo, pentoxifylline, nutritional therapy, antibiotics, immunomodulators, and antioxidants. Infection outcomes were inconsistently reported. Of 18 studies with available data, initial bacterial infections were reported in 46% and 24%. Follow-up infections were common, with bacterial infections most frequent, followed by fungal and viral types. Follow-up duration ranged from 6 days to 12 months, limiting comparability of infection-related outcomes. Conclusion: Significant heterogeneity in RCT design for corticosteroid use in alcoholic hepatitis particularly in dosing, initiation timing, tapering, and control arms hinders cross-trial comparisons and meta-analytic interpretation. Infections, a common and prognostically important complication, are inconsistently reported and variably defined. Standardized infection surveillance, uniform follow-up durations, and stratified reporting by infection type and timing are needed in future trials to better define the risk-benefit profile of corticosteroids in AH and guide clinical management.