Annualized fibrosis dynamics in metabolic dysfunction-associated steatotic liver disease: a paired-biopsy cohort

Abstract Background Fibrosis stage is the strongest histologic determinant of outcomes in metabolic dysfunction-associated steatotic liver disease (MASLD), but annualized fibrosis dynamics under routine care remain insufficiently quantified. We characterized fibrosis progression rate (FPR) in a long-term, pre-incretin paired-biopsy cohort to provide reference data for emerging metabolic therapies. Methods We analyzed 153 patients with MASLD who underwent repeat liver biopsy at a single center over a median interval of 5.9 years (range, 0.5–24). No patient received a GLP-1 receptor agonist or a dual GLP-1/GIP receptor agonist during follow-up. FPR was defined as the annualized change in fibrosis stage (stage/year). Factors associated with fibrosis improvement were examined using multivariable logistic regression. Results Fibrosis improved in 38 patients (25%), remained stable in 66 (43%), and progressed in 49 (32%). FPR varied substantially among patients with improvement or progression, revealing bidirectional and heterogeneous fibrosis dynamics not captured by categorical staging alone. FPR shifted in parallel with MASLD activity score change and was more closely related to changes in hepatocellular ballooning and lobular inflammation than to steatosis. Male sex, advanced baseline fibrosis, and ≥5% body weight reduction were associated with fibrosis improvement, with the likelihood increasing as these factors accumulated. Conclusion In this real-world pre-incretin paired-biopsy cohort, fibrosis change under routine care was bidirectional and heterogeneous, with wide variation in annualized rate. These data provide a reference for evaluating how emerging metabolic therapies modify the longitudinal course of MASLD.