Prospective study on time-to-tertiary care in alcohol-associated hepatitis: space-time coordinates as prognostic tool and therapeutic target

Background and aims Alcohol-associated hepatitis (AH) frequently triggers acute decompensation (AD) in cirrhosis, with severe AH linked to high short-term mortality, especially in acute-on-chronic liver failure. Current corticosteroid treatments have limited efficacy, highlighting the need for new therapies. We hypothesized that severe AH outcomes are influenced by early specialized care; thus, we examined the impact of time-to-tertiary care (TTTc). Methods Adults with cirrhosis or advanced chronic liver disease were enrolled (RH7, NCT04767945). AH was diagnosed using National Institute on Alcohol Abuse and Alcoholism criteria. Primary admission site, TTTc, and adverse outcomes (death or liver transplantation) were analyzed. Patients admitted directly to tertiary care were assigned a TTTc of zero. Results Of 221 AD-AH patients, 107 were transferred from secondary care to tertiary care (TTTc >0) and 114 were admitted directly (TTTc = 0). TTTc >0 patients were younger (48.3 vs. 52 years, P = .008) and had more severe disease, as shown by model for end-stage liver disease scores (25.5 vs. 20.8, P < .001) and Maddrey's discriminant function (59.3 vs. 40.6, P < .001). Propensity-score matching yielded 49 case pairs. The Cox model showed that transfer from secondary care was not associated with increased risk, but delayed transfer (days, hazard ratio = 1.03, 95% confidence interval 1.01-1.05) independently predicted adverse outcomes. Conclusions Delayed initiation of specialized care adversely impacts outcomes in AD-AH. If validated, timely care bundles could improve AH survival, similar to sepsis or vascular syndromes.