What is the clinical evidence from this study?

Study design: Cohort. Population: Nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), or at risk of NASH (n=81108). Intervention: FIB-4 index ≥2.67 vs. Established cardiovascular risk factors. Primary outcome: Major adverse cardiovascular events (MACE) defined by myocardial infarction, hospitalization for unstable angina or heart failure, and coronary revascularization (aHR 1.80, 95% CI 1.61-2.02, p=<0.001).

What does this research mean for the field?

A FIB-4 index ≥2.67 is the strongest independent predictor of major adverse cardiovascular events in patients with nonalcoholic fatty liver disease or nonalcoholic steatohepatitis, beyond established cardiovascular risk factors. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

January 18, 2022

Fibrosis-4 Index Can Independently Predict Major Adverse Cardiovascular Events in Nonalcoholic Fatty Liver Disease

Q: What are the key findings of this study?

A FIB-4 index ≥2.67 was the strongest independent predictor of MACE in patients with NAFLD or NASH (aHR 1.80; 95% CI 1.61-2.02; P<0.001).

Q: What does this research mean for the field?

A FIB-4 index ≥2.67 is the strongest independent predictor of major adverse cardiovascular events in patients with nonalcoholic fatty liver disease or nonalcoholic steatohepatitis, beyond established cardiovascular risk factors. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Key Result

A FIB-4 index ≥2.67 was the strongest independent predictor of MACE in patients with NAFLD or NASH (aHR 1.80; 95% CI 1.61-2.02; P<0.001).

Study Design

Type

Cohort (n=81,108)

Structured PICO

Does the fibrosis-4 index (FIB-4) independently predict major adverse cardiovascular events in patients with nonalcoholic fatty liver disease?

Population

81,108 patients with nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), or at risk of NASH. Mean age 62 years, 49.6% men. Analysis focused on 67,273 patients without previous cardiovascular disease.

Intervention

Fibrosis-4 index (FIB-4) score ≥2.67

Comparator

Lower FIB-4 scores

Outcome

Major adverse cardiovascular events (MACE) defined by myocardial infarction, hospitalization for unstable angina or heart failure, and coronary revascularization over median 3 years follow-upcomposite

In patients with NAFLD or NASH, a FIB-4 score ≥2.67 is a strong, independent predictor of major adverse cardiovascular events, suggesting its utility in cardiovascular risk stratification.

Main Result

Effect estimate: aHR 1.80 (95% CI 1.61-2.02)

p-value: p=<0.001

Abstract

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is closely associated with an increased risk of cardiovascular disease. We aimed to determine whether the fibrosis-4 index (FIB-4) can identify patients with NAFLD at highest risk of cardiovascular events. METHODS: We analyzed data from 81,108 patients with (i) a diagnosis of NAFLD, (ii) nonalcoholic steatohepatitis (NASH), or (iii) at risk (RISK) of NASH. The outcome of interest was major adverse cardiovascular events (MACE) defined by myocardial infarction, hospitalization for unstable angina or heart failure, and coronary revascularization. RESULTS: The mean age was 62 years, and 49.6% were men. Among 67,273 patients without previous cardiovascular disease, 9,112 (13.5%) experienced MACE over median follow-up of 3 years. In univariate analysis, a FIB-4 ≥2.67 was a significant predictor of MACE overall (hazard ratio HR 1.82, 95% confidence interval CI 1.63-2.04, P < 0.001) and across all baseline groups. After adjusting for established cardiovascular risk factors, FIB-4 ≥2.67 remained the strongest predictor of MACE overall (adjusted HR aHR 1.80, 95% CI 1.61-2.02, P < 0.001) and was consistently associated with myocardial infarction (aHR 1.46, 95% CI 1.25-1.70, P < 0.001), hospitalization for unstable angina (aHR 1.24, 95% CI 1.03-1.49, P = 0.025), hospitalization for heart failure (aHR 2.09, 95% CI 1.86-2.35, P < 0.001), coronary artery bypass graft (aHR 1.65, 95% CI 1.26-2.17, P < 0.001), and percutaneous coronary intervention (aHR 1.72, 95% CI 1.21-2.45, P = 0.003). DISCUSSION: In a large, real-world cohort of patients with NAFLD, NASH, or at RISK of NASH, the FIB-4 score was the strongest independent predictor of MACE, beyond established cardiovascular risk factors and baseline liver diagnosis.

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