Relationship between liver biopsy fibrosis stage and clinical outcomes among persons with MASLD/MASH in a real-world setting

Question: Metabolic dysfunction-associated steatohepatitis (MASH) is a common cause of liver-related morbidity and mortality. Liver biopsy is the reference standard for MASH diagnosis and disease status often relies on surrogate endpoints such as histologic markers. This analysis investigated the relationship between change in liver fibrosis stage over time and incidence of clinical outcomes among patients with MASH in a real-world setting.

Methodology: This analysis includes adults with 2 liver biopsies in TARGET-NASH, an ongoing observational study with 6,000+people with MASLD. They were classified into subgroups based on change in fibrosis stage: stabilized/improved (S/I, no change/reduction in fibrosis stage) or worsened (W, increase in fibrosis stage). Incidence of clinical outcomes (clinical evidence of progression to cirrhosis, decompensation, hepatocellular carcinoma [HCC], MELD score change, liver transplant [LT], cardiovascular [CV] event, all-cause mortality, cancer [excluding HCC, skin cancer]) stratified by index fibrosis stage and subgroups were studied. Hazard ratios were estimated with modified Fine-Gray regression models and time-varying covariates.

Results: 216 participants, median age 52 years, median BMI 33 kg/m2, 77% non-Hispanic White, 64% female, and 62% with type 2 diabetes (T2D) were included. Presence of T2D was greater with higher index fibrosis stage (F0/F1=49%, F4=71%, p=0.03). Significant association was noted between fibrosis stage and age at index (F0/F1=49,F4=56; p=0.01); no association was found between demographics, behavioral/lifestyle characteristics by disease progression subgroup. Patients with S/I fibrosis stage had lower prevalence of cirrhosis progression (S/I=34%, W=71%, p<0.0001). LT occurred during follow up among those with F3 (n=3) or F4 (n=13) (p<0.0001 vs. F0/1) at index (median time to LT: 7 and 3 years, respectively). Fibrosis worsening at any time was associated with increased probability of cirrhosis progression (F2=0.55,F3=0.67). T2D diagnosis at any time was associated with higher probability of cirrhosis progression (0.68 vs no T2D). Higher fibrosis stage at any time had higher probability of developing decompensation during follow up (F2=0.34,F3=0.58,F4=0.80, vs F0/F1). Older patients were more likely to have a CV event (HR=1.23, 95% CI 1.08,1.41). Fibrosis worsening at any time was associated with higher incidence of cancer. In F0-F3, incidence rate of any event after index was highest among index F3 followed by index F2 (incidence rate per 100 person years=13.2 and 9.84, respectively).

Conclusion: Higher index fibrosis stage and fibrosis worsening over time were associated with higher risk of clinical outcomes: progression to cirrhosis, decompensation, and cancer. Those with T2DM had an increased risk of progression to cirrhosis. These results, consistent with other literature, demonstrate the association of fibrosis surrogate endpoints and clinical events in a real world setting.

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Artikel online veröffentlicht:
28. Mai 2025