Association between invasive and noninvasive liver disease assessments and long-term clinical outcomes in MASLD.

Background and aims: Data are limited on how histology and noninvasive tests (NITs) for fibrosis severity in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) can predict future events. We aimed to confirm the prognostic capacity of liver fibrosis to predict major adverse liver outcomes (MALO), and to confirm previous findings of similar prognostic capacity between invasive and noninvasive fibrosis tests on long-term outcomes.

Methods: This longitudinal observational cohort study (1974-2020) used data from adults with biopsy-defined MASLD from three Swedish university hospitals linked to national registers. Risks for MALO and major adverse cardiovascular events (MACE) were estimated using multivariable adjusted Cox regression models.

Results: Median (mean) follow-up for the overall population (N = 959) was 11 (15) years; 103 (10.7%) developed MALO and 245/867 patients without baseline cardiovascular disease (28.3%) developed MACE. The risk of long-term MALO was significantly lower in patients at fibrosis stage F0, F1 and F2, compared with F4, but not between stages F3 and F4. No significant associations were observed between other histological features and incident MALO. Neither fibrosis stage nor histological features were significantly associated with incident MACE. Biopsy-defined fibrosis staging and Fibrosis-4 Index (FIB-4) scoring had similar predictive performance with unadjusted C-index (95% confidence interval) values for MALO of 0.77 (0.71-0.82) and 0.75 (0.69-0.80) and for cardiovascular-related outcomes 0.58 (0.53-0.60) and 0.65 (0.61-0.68), respectively.

Conclusions: These data confirm the importance of liver fibrosis as the main predictor of long-term MALO. FIB-4 may aid in risk assessment and in predicting outcomes in MASLD.