Advanced Liver Fibrosis Predicts Liver Outcomes in Biopsy-proven Metabolic Dysfunction-associated Steatotic Liver Disease: A U.S.-based Single-center Retrospective Cohort Study.

Background and Aims: Data regarding risk factors and long-term outcomes of U.S. patients with biopsy-proven metabolic dysfunction-associated steatotic liver disease (MASLD) are limited. This study aimed to investigate the role of clinical and histologic risk factors on long-term outcomes in patients with MASLD. Methods: A retrospective cohort study of 451 adults with biopsy-proven MASLD was conducted at a U.S. academic hospital from 2012 to 2020. An experienced pathologist evaluated the index liver biopsy. Patients with a prior liver transplant or alternative etiologies of chronic liver disease were excluded. The duration of the risk exposure was determined from the date of the index liver biopsy to an outcome event or the last follow-up examination. Outcome events of interest included incident liver-related events, liver decompensation, and all-cause mortality. Results: In the final cohort of 406 patients followed for a median of 3.7 years (interquartile range: 4.8 years), 35 patients died, 41 developed hepatic decompensation, and 70 experienced a liver-related event. Among histologic risk factors, stage 3 (adjusted Hazard ratio (aHR) 2.68, 95% confidence interval (CI) 1.18-6.11) and stage 4 (aHR 6.96, 95% CI 3.55-13.64) fibrosis were associated with incident liver-related events compared to stage 0-1 fibrosis. Stage 4 (aHR 8.46, 95% CI 3.26-21.99) fibrosis alone was associated with incident liver decompensation events compared to stage 0-1 fibrosis. Among clinical risk factors, hypertension (aHR 2.58, 95% CI 1.05-6.34) was associated with incident liver decompensation. Conclusions: In a U.S. single-center cohort of patients with biopsy-proven MASLD, advanced fibrosis was the primary risk factor for incident liver decompensation and liver-related events.