Dysregulated adipose tissue metabolism has been implicated in the pathogenesis of alcoholic liver disease in murine models. We aimed to characterize serum markers of adipose tissue metabolism and inflammation in patients with severe acute alcoholic hepatitis (AAH) and determine their utility to predict survival in severe AAH.

A prospective, case–control study design was used. Seventy‐six patients hospitalized with severe AAH and 25 ambulatory patients with alcoholic cirrhosis as controls were included. Serum samples were collected for biochemical analyses. Patients were followed for 180 days after enrollment to determine the survival.

AAH patients exhibited higher serum glycerol and free fatty acid levels, suggesting enhanced adipose tissue triglyceride hydrolysis. Patients with AAH demonstrated a distinct serum lipidomic profile compared with alcoholic cirrhosis but not in systemic and adipose‐specific insulin resistance. AAH patients had higher serum resistin and plasmin activation inhibitor‐1 levels, while serum leptin was decreased. Serum levels of the prolipolytic cytokines tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐6, IL‐8, and IL‐15 were significantly higher in AAH patients. Only 53% of AAH patients survived 180 days after admission, while all cirrhotic patients were alive at the end of the study period. Among patients with severe AAH, white blood cell count, hemoglobin, resistin, IL‐6 and TNF‐α were associated with 180‐day survival, and all 5 markers demonstrated accuracy by area under receiver–operator curve analysis. Serum IL‐6 levels ≥38.66 pg/ml most precisely identified deaths in severe AAH. Patients with IL‐6 ≥ 38.66 pg/ml had significantly decreased mean survival compared to those with lower levels.

AAH patients demonstrate evidence of increased adipose tissue lipolysis and altered serum lipidomic profile compared with alcoholic cirrhosis patients. IL‐6 may be a useful biomarker to risk stratify severe AAH patients at the highest risk of mortality.