Relationship between updated MELD and prognosis in alcohol-associated hepatitis: Opportunities for more efficient trial design

Abstract

Liver disease; Prognosis; Alcohol-associated hepatitis

Malaltia del fetge; Pronòstic; Hepatitis associada a l'alcohol

Enfermedad del hígado; Pronóstico; Hepatitis asociada al alcohol

Background: Alcohol-associated hepatitis (AH) is associated with significant mortality. Model for End-Stage Liver Disease (MELD) score is used to predict short-term mortality and aid in treatment decisions. MELD is frequently updated in the course of AH. However, once the most updated MELD is known, it is uncertain if previous ones still have prognostic value, which might be relevant for transplant allocation and trial design. We aimed to investigate the predictive performance of updated MELDs in a prospectively collected cohort of patients with AH by the InTeam consortium. Methods: Three hundred seven patients (with 859 MELD values within 60 d of admission) fulfilled the inclusion criteria. The main endpoint was time to death or transplant up to 90 days. We used a joint model approach to assess the predictive value of updated MELDs. Results: Updated MELD measurements had a strong prognostic value for death/transplant (HR: 1.20, 95% CI: 1.14–1.27) (p < 0.0001). Previous MELD values did not add predictive value to the most current MELD. We also showed that MELD at day 28 (MELD28) had a significant predictive value for subsequent mortality/transplant in a landmark analysis (HR: 1.18, 95% CI: 1.12–1.23). We show that the use of an ordinal scale including death, transplant, and MELD28 as a trial outcome could substantially reduce the sample size required to demonstrate short-term benefit of an intervention. Conclusion: We show that updated MELDs during the trajectory of AH predict subsequent mortality or the need for transplant. MELD28 inclusion in an ordinal outcome (together with death or transplant) could increase the efficiency of randomized controlled trials.

This study was supported by the National Institutes on Alcohol Abuse and Alcoholism (NIAAA U01AA021908). Meritxell Ventura-Cots received financial support from JR19/00015 and PI22/01770. Bernd Schnabl is supported by NIH center P30 DK120515.