Association of Index and Changes in Fibrosis-4 Score With Outcomes in Metabolic Dysfunction-Associated Steatohepatitis

Background and Aims: This study assessed the relationship between Fibrosis-4 (FIB-4) scores at time of initial metabolic dysfunction-associated steatohepatitis (MASH) diagnosis, as well as subsequent changes in these scores over time, and any adverse hepatic and extrahepatic outcomes. Methods: This study retrospectively analyzed administrative claims data from patients with a MASH diagnosis between 2015 and 2022. Patients were categorized based on risk of advanced fibrosis (low, indeterminate, and high) using FIB-4 score calculated at index (date of FIB-4 score within ±180 days of MASH diagnosis) and longitudinally. Adjusted hazard ratios (aHRs) and confidence intervals (CIs) were estimated to determine associations between index and longitudinal changes in FIB-4, and hazard of major adverse liver outcomes (MALO) and major adverse cardiovascular events (2-point assessment; MACE-2pt). Results: A total of 17,511 and 19,395 patients with an index FIB-4 score were included in the MALO and MACE-2pt analyses, respectively. Cohorts with longitudinal FIB-4 scores comprised 10,655 and 11,934 patients for the 2 respective outcomes. High-risk FIB-4 score at index was significantly associated with higher hazard of MALO (aHR: 4.29; 95% CI: 3.87-4.77) and MACE-2pt (aHR: 1.44; 95% CI: 1.25-1.66) compared with low risk. Progression from low-risk to high-risk FIB-4 score was associated with a higher hazard of MALO (aHR: 2.62; 95% CI: 1.92-3.58), vs remaining at low risk. This was also found for progression from indeterminate-risk to high-risk FIB-4 score (aHR: 1.94; 95% CI: 1.50-2.53). Conclusion: High-risk index FIB-4 and increases in FIB-4 are associated with increased hazard of MALO and MACE. Thus, in patients diagnosed with MASH, FIB-4 scores could serve as an important noninvasive and prognostic tool for adverse cardiovascular and liver outcomes.