Association Found Between Liver Fibrosis and HFpEF, Research Needed to Identify Causal Interactions

human liver
Researchers assessed the prevalence of liver fibrosis in patients with HFpEF and the relationships of these biomarkers in predicting clinical outcomes of patients.

Liver fibrosis is found in a relatively sizeable proportion of patients with heart failure with preserved ejection fraction (HFpEF), according to a study in ESC Heart Failure.

This study included patients from the TOPCAT study, which examined spironolactone compared with placebo for HFpEF. Researchers of this analysis of the TOPCAT participants used clinical characteristics and laboratory parameters of 1423 participants with HFpEF to calculate nonalcoholic fatty liver disease fibrosis score (NFS) and fibrosis-4 (FIB-4) scores.

Based on these scores, patients were classified as having a low-, intermediate-, or high-risk of advanced fibrosis. Researchers also examined the association between the risk of fibrosis severity and a combined primary endpoint composed of cardiovascular death, aborted cardiac arrest, and hospitalization for heart failure.

The NFS and FIB-4 identified 37.57% and 8.02% of advanced fibrosis cases, respectively, whereas fibrosis severity was considered indeterminate in 51.25% of patients. Older age was generally associated with a higher risk of advanced hepatic fibrosis across NFS and FIB-4 groups.

The crude risk of advanced fibrosis was significantly associated with the primary cardiovascular outcome (NFS high vs low: hazard ratio [HR], 1.709; 95% CI, 1.238-2.358; P =.0011; FIB-4 high vs low: HR, 1.561; 95% CI, 1.139-2.140; P =.0056). According to a multivariable adjusted analysis, the significant association disappeared (NFS high vs low: HR, 1.349; 95% CI, 0.938-1.939; P =.1064; FIB-4 high vs low: HR, 1.415; 95% CI, 0.995-2.010; P =.0531).

A limitation of this study included its post hoc design, which the investigators suggest reduces the ability to identify direct causality between liver fibrosis and HFpEF.

Given the limitations, the investigators note that further research “is necessary to better understand the complex interplay between chronic liver disease and HFpEF and determine whether there are any clear causal interactions.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Peters AE, Pandey A, Ayers C, et al. Association of liver fibrosis risk scores with clinical outcomes in patients with heart failure with preserved ejection fraction: findings from TOPCAT. ESC Heart Fail. Published online February 14, 2021. doi:10.1002/ehf2.13250