FIB‐4 and incident severe liver outcomes in patients with undiagnosed chronic liver disease: A Fine‐Gray competing risk analysis

Background and Aims The Fibrosis‐4 index (FIB‐4) can reliably assess fibrosis risk in patients with chronic liver disease, and advanced fibrosis is associated with severe liver disease (SLD) outcomes. However, CLD is underdiagnosed in primary care. We examined the association between FIB‐4 risk strata and the incidence of SLD preceding a CLD diagnosis while considering incident CLD diagnoses as competing risks. Methods Using primary care clinic data between 2007 and 2018, we identified patients with two FIB‐4 scores and no liver disease diagnoses preceding the index FIB‐4. Patients were followed from index FIB‐4 until an incident SLD (a composite of cirrhosis, hepatocellular carcinoma or liver transplantation), CLD or were censored. Hazard ratios were computed using a Fine‐Gray competing risk model. Results Of 20 556 patients, there were 54.8% in the low, 34.8% in the indeterminate, 6.6% in the high and 3.8% in the persistently high‐risk FIB‐4 strata. During a mean 8.2 years of follow‐up, 837 (4.1%) patients experienced an SLD outcome and 11.5% of the sample received a CLD diagnosis. Of patients with an SLD event, 49% received no preceding CLD diagnosis. In the adjusted Fine‐Gray model, the indeterminate (HR 1.41, 95% CI 1.17–1.71), high (HR 4.65, 95% CI 3.76–5.76) and persistently high‐risk (HR 7.60, 95% CI 6.04–9.57) FIB‐4 risk strata were associated with a higher incidence of SLD compared to the low‐risk stratum. Conclusions FIB‐4 scores with indeterminate‐ and high‐risk values are associated with an increased incidence of SLD in primary care patients without known CLD.