Association between longitudinal biomarkers and major adverse liver outcomes in patients with non-cirrhotic metabolic dysfunction-associated steatotic liver disease

Background and Aims: Noninvasive biomarkers provide prognostic information for the development of major adverse liver outcomes (MALOs) in patients with metabolic dysfunction–associated steatotic liver disease (MASLD), but the predictive value of longitudinal biomarker measurements has not been evaluated. We assessed whether changes in biomarkers could predict incident MALO in MASLD. Approach and Results: We analyzed a cohort of 1260 patients (71.7% on biopsy) with non-cirrhotic MASLD between 1974 and 2019. Data at baseline and follow-up visits were obtained from medical charts. MALO was determined through medical charts and linkage to national registers until the end of 2020. A joint modeling approach was used to quantify the associations between the trajectory of biomarkers and the risk of MALO. MASLD was diagnosed at a median age of 52 years (IQR: 39–60), and 59% were male. During a median follow-up of 12.2 years, 111 (8.8%) patients developed MALO. The joint modeling showed that an elevated fibrosis-4 score (HR: 2.60, 95% CI: 1.89–3.50), aspartate aminotransferase (HR: 2.69, 95% CI: 2.57–3.05), and lower platelet count (HR: 0.93, 95% CI: 0.90–0.97) at any time point were associated with an increased risk of MALO, whereas the rate of change in these biomarkers had no association with this risk. Conclusions: In addition to baseline measurements of noninvasive biomarkers such as fibrosis-4 score, aspartate aminotransferase, and platelets taken at MASLD diagnosis, monitoring their values over time is important, as the latest value of these biomarkers is closely associated with the risk of future MALO. The rate of change may not be as important.