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Liver fibrosis assessed via non-invasive tests is associated with incident heart failure in a general population cohort

Liver fibrosis assessed via non-invasive tests is associated with incident heart failure in a general population cohort
Liver fibrosis assessed via non-invasive tests is associated with incident heart failure in a general population cohort
Aims: 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 non-invasive fibrosis markers [NAFLD fibrosis score (NFS), Fibrosis-4 (FIB-4) and AST to platelet ratio index (APRI)] and incident hospitalization/death from heart failure (n=413,860). Cox-regression estimated hazard ratios (HR) 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: 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 [1.47-1.76], p<0.0001; FIB-4 HR 1.69 [1.55-1.84], p<0.0001; APRI HR 1.85 [1.56-2.19], p<0.0001; combined fibrosis scores HR 1.90 [1.44-2.49], p<0.0001). 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.
Cirrhosis, Fibrosis, Heart Failure
1542-3565
1657-1667
Hydes, Theresa J.
b92d7e13-6663-414d-9fc8-d5bfbf82489e
Kennedy, Oliver J.
96f5e8fc-f18e-4887-8504-77ffef83c7f1
Glyn-Owen, Kate
046b9ac1-ab79-4786-af26-f1a2f96ddc05
Buchanan, Ryan
9499f713-f684-4046-be29-83cd9d6f834d
Parkes, Julie
59dc6de3-4018-415e-bb99-13552f97e984
Cuthbertson, Daniel J.
39aca7a0-9f7b-45fe-8c3c-d973cc5ac5b1
Roderick, Paul
dbb3cd11-4c51-4844-982b-0eb30ad5085a
Byrne, Christopher D.
1370b997-cead-4229-83a7-53301ed2a43c
et al.
Hydes, Theresa J.
b92d7e13-6663-414d-9fc8-d5bfbf82489e
Kennedy, Oliver J.
96f5e8fc-f18e-4887-8504-77ffef83c7f1
Glyn-Owen, Kate
046b9ac1-ab79-4786-af26-f1a2f96ddc05
Buchanan, Ryan
9499f713-f684-4046-be29-83cd9d6f834d
Parkes, Julie
59dc6de3-4018-415e-bb99-13552f97e984
Cuthbertson, Daniel J.
39aca7a0-9f7b-45fe-8c3c-d973cc5ac5b1
Roderick, Paul
dbb3cd11-4c51-4844-982b-0eb30ad5085a
Byrne, Christopher D.
1370b997-cead-4229-83a7-53301ed2a43c

Hydes, Theresa J., Kennedy, Oliver J. and Glyn-Owen, Kate , et al. (2024) Liver fibrosis assessed via non-invasive tests is associated with incident heart failure in a general population cohort. Clinical Gastroenterology and Hepatology, 22 (8), 1657-1667. (doi:10.1016/j.cgh.2024.03.045).

Record type: Article

Abstract

Aims: 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 non-invasive fibrosis markers [NAFLD fibrosis score (NFS), Fibrosis-4 (FIB-4) and AST to platelet ratio index (APRI)] and incident hospitalization/death from heart failure (n=413,860). Cox-regression estimated hazard ratios (HR) 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: 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 [1.47-1.76], p<0.0001; FIB-4 HR 1.69 [1.55-1.84], p<0.0001; APRI HR 1.85 [1.56-2.19], p<0.0001; combined fibrosis scores HR 1.90 [1.44-2.49], p<0.0001). 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.

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Accepted/In Press date: 21 March 2024
e-pub ahead of print date: 8 May 2024
Published date: 1 August 2024
Keywords: Cirrhosis, Fibrosis, Heart Failure

Identifiers

Local EPrints ID: 489148
URI: http://eprints.soton.ac.uk/id/eprint/489148
ISSN: 1542-3565
PURE UUID: 28157eab-0d1a-4236-9428-82721c73743d
ORCID for Kate Glyn-Owen: ORCID iD orcid.org/0000-0001-7934-2684
ORCID for Ryan Buchanan: ORCID iD orcid.org/0000-0003-0850-5575
ORCID for Julie Parkes: ORCID iD orcid.org/0000-0002-6490-395X
ORCID for Paul Roderick: ORCID iD orcid.org/0000-0001-9475-6850
ORCID for Christopher D. Byrne: ORCID iD orcid.org/0000-0001-6322-7753

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Date deposited: 16 Apr 2024 16:30
Last modified: 12 Nov 2024 03:11

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Contributors

Author: Theresa J. Hydes
Author: Oliver J. Kennedy
Author: Kate Glyn-Owen ORCID iD
Author: Ryan Buchanan ORCID iD
Author: Julie Parkes ORCID iD
Author: Daniel J. Cuthbertson
Author: Paul Roderick ORCID iD
Corporate Author: et al.

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