Combination of Fibrosis-4, liver-stiffness measurement, and Fibroscan-AST score to predict liver-related outcomes in nonalcoholic fatty liver disease

Introduction: Noninvasive tests, such as Fibrosis-4 (FIB-4), liver-stiffness measurement (LSM) by vibration-controlled transient elastography, and Fibroscan-AST (FAST), are frequently used for risk stratification in NAFLD. The comparative performance of FIB-4 and LSM and FAST to predict clinical outcomes of patients with NAFLD remained unclear. We aim to evaluate the performance of FIB-4, LSM, and FAST scores to predict clinical outcomes in patients with NAFLD. Methods: We included consecutive adult patients with NAFLD with transient elastography performed between 2015 and 2022 from the United States and Singapore. Patients with NAFLD stratified based on baseline FIB-4, LSM, and FAST score were followed up until clinical outcomes notably liver-related events (LREs), LREs or death, death, and major adverse cardiac events. Results: A total of 1262 patients with NAFLD (63% with obesity and 37% with diabetes) with vibration-controlled transient elastography were followed up for median 3.5 years. FIB-4 stratified patients with NAFLD into low-risk (<1.3), intermediate-risk (1.3–2.67), and high-risk (>2.67) in 59.4%, 31.5%, and 9.1%, respectively. No LRE occurred with baseline FIB-4 <1.3, regardless of LSM and FAST score. Higher FIB-4 was associated with a higher risk of LREs within each LSM category. FIB-4 had a higher area under the received operating characteristic curve than LSM or FAST score to predict LRE. Conclusions: In this multicenter international study, FIB-4 and LSM synergistically predicted the risk of LRE. In patients with FIB-4 <1.3, vibration-controlled transient elastography may incorrectly classify up to 10% of the patients as high risk. FIB-4 should be incorporated into risk stratification in NAFLD even among patients who underwent VCTE.