Validation of FIB-4 for the Diagnosis of Liver Cirrhosis in Metabolic Dysfunction-Associated Steatotic Liver Disease.

American Association for the Study of Liver Diseases practice guidance on metabolic dysfunction-associated steatotic liver disease (MASLD) has recommended using specific cut-off values for the Fibrosis-4 index (FIB-4) to detect cirrhosis. A cut-off of 3.48 is recommended for identifying stage 4 fibrosis (F4) with high specificity, while a cut-off of 1.67 is suggested for ruling out advanced fibrosis. Our study aimed to validate the diagnostic performance of these new FIB-4 cut-offs in our cohort of biopsy-proven MASLD from two Canadian tertiary care centres. Our study included 390 patients with biopsy-proven MASLD with F4 prevalence of 22%. Among the 87 patients with cirrhosis, 37 (42.5%) were correctly identified with a FIB-4 ≥3.48. FIB-4 had an area under the receiver operating characteristic curve of 0.79 at the proposed cut-off points, with 32% of patients being indeterminate or misclassified. Sensitivity and positive-predictive value for the FIB-4 cut-off were 65% and 68.5%, respectively, while the specificity and negative-predictive value were 93% and 92%, respectively. In conclusion, in our biopsy-proven MASLD cohort, recommended FIB-4 cut-offs ≥3.48 and <1.67 had low sensitivity but high specificity. An upper FIB-4 cut-off of 3.48 would have missed nearly one in four cirrhosis cases. The proposed FIB-4 thresholds for identifying F4 in MASLD patients have limited diagnostic utility in higher prevalence tertiary hepatology cohorts.