Longitudinal Changes in Fibrosis Markers: Monitoring Stiffness/Fibrosis Progression and Prognostic Outcomes in MASLD

Background & Aims Fibrosis-4 Index (FIB-4) is a noninvasive tool for assessing liver fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD). However, its role of dynamic FIB-4 for assessing fibrosis progression and predicting clinical outcomes remains unclear. The aim of this study was to examine the association between changes in FIB-4 and changes in liver stiffness, fibrosis progression, and outcomes in MASLD. Methods Three cohorts were analyzed: VCTE-Prognosis cohort (n = 10,203) for stiffness progression, Paired Liver Biopsy cohort (n = 1,145) for fibrosis progression, and Wenzhou Real-World (WRW) cohort (n = 41,105) for clinical outcomes. Stiffness progression was defined as an increase in liver stiffness measurement, and fibrosis progression by a 1-stage increase. Outcomes included all-cause mortality, cardiovascular events, and liver-related events (LREs). FIB-4 was dichotomized into low (<1.3) and high (≥1.3). Increases were defined as ≥20% rise and to ≥1.3 in the low FIB-4 group, and ≥20% rise in the high FIB-4 group. Results In the VCTE-Prognosis cohort, stiffness progression was more likely with increasing vs stable FIB-4 (adjusted odds ratio [OR], 2.36; P < .001) in those with low baseline FIB-4. In the high FIB-4 group, stiffness progression rates increased from stable to increasing FIB-4 (adjusted OR, 3.42; P < .001). In the Paired Liver Biopsy cohort, fibrosis progression was more frequent with increasing FIB-4 (adjusted OR, 2.20; P = .004 in low FIB-4; adjusted OR, 3.68; P < .001 in high FIB-4). In the WRW cohort, an increase in dynamic FIB-4 was linked to higher risks for all-cause mortality, cardiovascular events, and LREs (all P < .001). Conclusions Dynamic FIB-4 monitoring tracks fibrosis and stiffness progression and predicts clinical outcomes in MASLD.