Change in fibrosis-4 index (fib4) over time is associated with subsequent risk of liver events, cardiovascular events, and all-cause mortality in patients with obesity and/or type 2 diabetes

Tools to monitor patients with non-alcoholic steatohepatitis (NASH) and assess their risk of morbidity and mortality are lacking. We evaluated the association of 12-month changes in fibrosis-4 index (ΔFIB4) with the risk of developing severe NASH-related clinical events. We conducted a longitudinal cohort study using data from the UK Clinical Practice Research Datalink linked with Hospital Episodes Statistics and Office for National Statistics data. Patients were aged ≥18 years; had obesity and/or type 2 diabetes (T2D); ≥2 FIB4 measurements; and no alcohol-related disorders, chronic liver diseases other than non-alcoholic fatty liver disease, or prescriptions of drugs inducing liver disease. We calculated ΔFIB4 using score at baseline and after 12 (±3) months. Patients were followed from second measurement until time of first liver event; time of first cardiovascular (CV) event (hospitalization/death); all-cause mortality; database migration; 10 years’ follow-up; or 1 Jan 2020, whichever was first. Cumulative incidence and HRs were estimated with Aalen-Johanson and Cox proportional hazards models. There were 466 liver events among 20,443 included patients. Risk of an incident liver event after 10 years in patients with high baseline FIB4 (>2.67) was 12.8%, but 18.5% and 10.1% for patients whose FIB4 increased or decreased in the 12 months from baseline (Figure). Patients with an indeterminate (1.30–2.67) or low baseline FIB4 ( < 1.30) also showed increased risk with increasing FIB4 and vice versa (Figure). In Cox models adjusted for sex, age, and baseline FIB4, ΔFIB4 was positively associated with the risk of a liver event, with the association depending on baseline FIB4. Thus, compared with patients with low baseline FIB4 and no change in FIB4 (reference), the HR (95% confidence interval) was 24.27 (16.98, 34.68) for those with high baseline FIB4 and a 1-unit FIB4 increase, and 10.90 (7.90, 15.05) for those with high baseline FIB4 and a 1-unit decrease. Compared with the reference, those with indeterminate and low baseline FIB4 and 1-unit FIB4 increase/decrease also had significantly higher/lower risk. Similar results were seen for CV events and mortality, though the association with CV events was attenuated after adjustment for age. In patients with obesity and/or T2D, a 12-month increase/decrease in FIB4 was associated with higher/lower risk of a NASH-related clinical event across all three FIB4 baseline groups, highlighting the monitoring potential of FIB4 to identify patients at risk of severe events.