Abstract Body (Do not enter title and authors here):
Background and aim:
The Fibrosis-4 (FIB-4) score is recommended as a first-line screening tool to rule-out advanced liver fibrosis. It is highly recommended to screen for liver fibrosis in patients with Type 2 diabetes mellitus (T2DM) and elevated liver enzymes using the fibrosis-4 (FIB-4) score.However, this recommendation does not extend to patients with chronic heart failure (CHF) who do not have T2DM. We aimed to investigate the predictors of high risk for advanced liver fibrosis according to the FIB-4 score and its association with all-cause and cardiovascular mortality, as well as major adverse liver outcomes (MALO), in patients with CHF, both with and without T2DM.

Methods:
This was a nationwide registry-based cohort study. We included patients registered in the Danish Heart Failure Registry who had laboratory data available to calculate FIB-4 scores from April 2003 to December 2019. Patients were classified as low-risk (Fib-4 <1.3), indeterminate-risk (1.3 – 2.67), and high-risk of advanced liver fibrosis (≥2.67). The analysis was conducted using multiple logistic regression and Cox proportional hazards models.

Results:
A total of 6079 patients with CHF were included in the study. High-risk of advanced liver fibrosis was highly prevalent, affecting 30% of the studied population. Predictors of high-risk of advanced liver fibrosis, included older age, male sex, severe chronic kidney disease, previous myocardial infarction, ischemic heart disease, and atrial fibrillation/flutter. Patients in the high-risk group exhibited a significantly elevated risk of all-cause mortality (HR: 1.30, 95% CI: 1.17-1.45), cardiovascular mortality (HR: 1.80, 95% CI: 1.49-2.17), as well as MALO (HR: 4.42, 95% CI: 2.70-7.23) when compared to those in the low-risk group. This was regardless of the presence of T2DM. Additionally, patients in the indeterminate-risk group showed an increased risk of cardiovascular mortality (HR: 1.22, 95% CI: 1.02-1.46) and MALO (HR: 1.86, 95% CI: 1.13-3.06) when compared to the low-risk group.

Conclusion:
In this nationwide cohort study, we found a high prevalence of high-risk of advanced liver fibrosis according to the FIB-4 score. Several clinical predictors of high-risk of liver fibrosis was identified. High-risk patients exhibited significantly higher all-cause and cardiovascular mortality, as well as major adverse liver outcomes (MALO), compared to low-risk patients, independent of T2DM status.