Liver fibrosis Assessed Via Non-invasive Tests is Associated With Incident Heart Failure in a General Population Cohort

Theresa J Hydes; Oliver J Kennedy; Kate Glyn-Owen; Ryan Buchanan; Julie Parkes; Daniel J Cuthbertson; Paul Roderick; Christopher D Byrne

doi:10.1016/j.cgh.2024.03.045

Liver fibrosis Assessed Via Non-invasive Tests is Associated With Incident Heart Failure in a General Population Cohort

Clin Gastroenterol Hepatol. 2024 May 8:S1542-3565(24)00408-7. doi: 10.1016/j.cgh.2024.03.045. Online ahead of print.

Authors

Theresa J Hydes¹, Oliver J Kennedy², Kate Glyn-Owen², Ryan Buchanan³, Julie Parkes², Daniel J Cuthbertson⁴, Paul Roderick², Christopher D Byrne⁵

Affiliations

¹ Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, Faculty of Health & Life Sciences, University of Liverpool, Liverpool, United Kingdom; University Hospital Aintree, Liverpool University Hospitals NHS Foundation Trust, Liverpool, United Kingdom; Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool, United Kingdom. Electronic address: theresa.hydes@liverpool.ac.uk.
² Primary Care, Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
³ Primary Care, Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; Southampton National Institute for Health and Care Research, Biomedical Research Centre, University Hospital Southampton, Southamptom, United Kingdom.
⁴ Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, Faculty of Health & Life Sciences, University of Liverpool, Liverpool, United Kingdom; University Hospital Aintree, Liverpool University Hospitals NHS Foundation Trust, Liverpool, United Kingdom; Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool, United Kingdom.
⁵ Southampton National Institute for Health and Care Research, Biomedical Research Centre, University Hospital Southampton, Southamptom, United Kingdom; Nutrition and Metabolism, Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.

PMID: 38723982
DOI: 10.1016/j.cgh.2024.03.045

Abstract

Background & aims: The aim of this study was to determine whether liver fibrosis is associated with heart failure in a general population cohort, and if genetic polymorphisms (PNPLA3 rs738409; TM6SF2 rs58542926), linked to increased risk of liver fibrosis and decreased risk of coronary artery disease, modify this association.

Methods: Using UK Biobank data, we prospectively examined the relationship between noninvasive fibrosis markers (nonalcoholic fatty liver disease [NAFLD] fibrosis score [NFS], Fibrosis-4 [FIB-4] and aspartate transaminase [AST] to platelet ratio index [APRI]) and incident hospitalization/death from heart failure (n = 413,860). Cox-regression estimated hazard ratios (HRs) for incident heart failure. Effects of PNPLA3 and TM6SF2 on the association between liver fibrosis and heart failure were estimated by stratifying for genotype and testing for an interaction between genotype and liver fibrosis using a likelihood ratio test.

Results: A total of 12,527 incident cases of heart failure occurred over a median of 10.7 years. Liver fibrosis was associated with an increased risk of hospitalization or death from heart failure (multivariable adjusted high-risk NFS score HR, 1.59; 95% confidence interval [CI],1.47-1.76; P < .0001; FIB-4 HR, 1.69; 95% CI, 1.55-1.84; P < .0001; APRI HR, 1.85; 95% CI, 1.56-2.19; P < .0001; combined fibrosis scores HR, 1.90; 95% CI, 1.44-2.49; P < .0001). These associations persisted for people with metabolic dysfunction-associated steatotic liver disease (MASLD), MASLD with alcohol consumption (Met-ALD), and harmful alcohol consumption. PNPLA3 rs738409 GG and TM6SF2 rs58542926 TT did not attenuate the positive association between fibrosis markers and heart failure. For PNPLA3, a statistically significant interaction was found between PNPLA3 rs738409, FIB-4, APRI score, and heart failure.

Conclusion: In the general population, serum markers of liver fibrosis are associated with increased hospitalization/death from heart failure. Genetic polymorphisms associated with liver fibrosis were not positively associated with elevated heart failure risk.

Keywords: Cirrhosis; Fibrosis; Heart Failure.