The INTEGRATE prospective cohort study: Design and methods to evaluate biopsychosocial determinants of outcomes in early liver transplantation for alcohol-associated liver disease

BACKGROUND AND AIMS: Early liver transplantation (eLT) for alcohol-associated liver disease (ALD), defined as transplant evaluation with <6 months of alcohol abstinence, is a life-saving therapy for select patients. However, critical gaps remain in understanding patient selection, management strategies, and longitudinal outcomes. To address these gaps, the multi-disciplinary INTEGRATE Collaborative was established to conduct 5 parallel studies using a mixed-methods research approach to comprehensively address these gaps. This manuscript describes the design and methods of the INTEGRATE cohort study, which aims to identify the biopsychosocial factors causally related to and predictive of stakeholder-relevant outcomes. METHODS AND RESULTS: The INTEGRATE cohort study is a prospective multicenter, longitudinal, observational study enrolling up to 680 adults with ALD undergoing evaluation for eLT at 4 U.S. centers. Participants are followed from transplant evaluation initiation through key pre-transplant and post-transplant milestones, with planned outcome surveillance for a minimum of 36 months, and longer as data are available. Data collection includes detailed alcohol use assessments, psychosocial and behavioral measures, clinical data, imaging, and biospecimen banking. The cohort is designed to identify biopsychosocial factors associated with and predictive of survival, waitlisting, alcohol-associated outcomes, healthcare utilization, and post-transplant clinical and patient-reported outcomes. CONCLUSIONS: The prospective INTEGRATE cohort study provides a rigorous observational foundation to inform patient selection, management, and outcome prediction in eLT for ALD. This method's manuscript details the cohort design to promote transparency, reproducibility, and integration with complementary INTEGRATE studies.