Validation of a Clinical Risk-based Classification System in a Large Nonalcoholic Fatty Liver Disease Real-world Cohort

Background & Aims: There is an unmet need to validate simple and easily available methods that can be used in routine practice to identify those at risk of adverse outcomes from nonalcoholic fatty liver disease (NAFLD). A retrospective-prospective analysis of NAFLD patients enrolled in a longitudinal noninterventional study (TARGET-NASH) was performed to validate the prognostic utility of the following risk-categories: (A) Fibrosis-4 (FIB-4) <1.3 and/or liver-stiffness measurement (LSM) measured by Fibroscan <8 kp, (B) FIB-4 1.31‒2.6 and/or LSM 8.1-12.5 kp, and (C) FIB-4 >2.6 and/or LSM >12.5 kp. Methods: Those in class A with aspartate transaminase:alanine transaminase ratio >1 or platelets <150,000/mm³, or class B with aspartate transaminase:alanine transaminase ratio >1 or platelets <150,000/mm³ were upstaged by one class. Fine-Gray competing risk analyses were performed for all outcomes. Results: A total of 2523 individuals (class A = 555, B = 879, C = 1089) were followed for a median duration of 3.74 years. Adverse outcomes increased from class A to C in all-cause mortality (0.07 vs 0.3 vs 2.5/100 person-years [PY], hazard ratio [HR], 3.0 and 16.3 class B and C vs A), liver-associated clinical events (0.2 vs 1 vs 8/100 PY, HR, 4.3 and 36.6 B and C vs A), major adverse cardiovascular events (0.69 vs 0.87 vs 2.02/100 PY, HR, 0.78 and 1.55 B and C vs A), hepatocellular carcinoma (0 vs 0.09 vs 0.88/100 PY, HR, 8.32 C vs B), and chronic kidney disease (1.24 vs 2.48 vs 3.51/100 PY). Those who were upstaged had outcome rates similar to the lower class defined by their FIB-4. Conclusions: These data support a FIB-4-based risk-stratification of NAFLD that can be used in routine clinical practice. ClinicalTrials.gov