LAUSR

BACKGROUND & AIMS Patients with severe alcohol-associated hepatitis (AH) have high mortality. Corticosteroids improve survival only for 30 days. We targeted inflammation, cellular injury and gut leakiness in a randomized clinical trial comparing combination therapy to corticosteroids on 180-day survival. APPROACH & RESULTS Subjects with a clinical diagnosis of severe AH (MELD>20, MDF>32) were randomized to receive methylprednisolone (28 days) (PRED) or a combination of anakinra (14 days) plus pentoxifylline (28 days) plus zinc (180 days) (COMB). The primary endpoint was survival at 180 days. The study was designed in 2013, initiated in October 2014 and completed in March 2018. Five hundred (500) patients were screened to randomize 104 subjects with a clinical diagnosis of AH with a Model for End Stage Liver Disease (MELD) score > 20. Fifty-three (53) patients were randomized into the COMB and fifty (50) to the PRED treatment; one dropped out of the study before randomization. The mean age was 45.3±10.4 years. 60.6% were males, 92.3% white, mean MELD 25.7±3.9. Kaplan-Meier survival estimate at 180-day was 67.9% in COMB and 56% in PRED (HR=0.69; p=0.3001). Survival curves separated by 90 days (COMB: 69.8%; PRED: 58.0%; HR=0.69, p=0.28). Survival at 28 days was similar between the COMB (83.4%) and PRED groups (81.2%) (HR=0.91, p=0.85). There were no unexpected serious adverse events and the incidence of infection was comparable between groups. MELD 20-25 and MELD >26 strata showed non-significant treatment effects in favor of COMB. CONCLUSIONS A combination of anakinra, pentoxifylline plus zinc provides similar survival benefits compared to corticosteroid therapy in severe AH.