Skip to main content
SpringerLink
Log in

Liver fibrosis and outcomes of atrial fibrillation: the FIB-4 index

  • Original Paper
  • Published:
Clinical Research in Cardiology Aims and scope Submit manuscript

Abstract

Background and aims

Liver diseases play an important role in the development and progression of atrial fibrillation (AF). The Fibrosis-4 (FIB-4) index is a non-invasive score recommended for detecting liver fibrosis. Since the association between liver fibrosis and outcomes of AF patients is still not well defined, we aim to analyze prognosis impact of FIB-4 index in those patients.

Methods

A retrospective population-based cohort study was performed with 12,870 unselected patients from a single health area in Spain with AF from 2014 to 2019. Cox regression models were used to estimate the association of FIB-4 index with mortality. The association with ischemic stroke (IS), major bleeding (MB), acute myocardial infarction (AMI), and heart failure (HF) was assessed by competing risk analysis.

Results

A total of 61.1%, 22.0%, and 16.9% were classified as low, moderate and high risk of liver fibrosis according to FIB-4 index, respectively. During a mean follow-up of 4.5 ± 1.7 years, FIB-4 index was associated with mortality (adjusted HR 1.04; 95% CI 1.01–1.06; p = 0.002), MB and HF (adjusted sHR 1.03, 95% CI 1.01–1.04; p = 0.004), but not with IS or with AMI. The association between FIB-4 and MB was only found in patients treated with vitamin K antagonists, not in patients on direct oral anticoagulants.

Conclusions

The FIB-4 index, a non-invasive scoring method for evaluating liver fibrosis, is independently associated with all-cause mortality, MB and HF in patients with AF, suggesting that it may be useful as a risk assessment tool to identify adverse outcomes in patients with AF.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

Data included in this study will be made available. Requests for the data from CadioCHUVI-AF registry should be made to the corresponding author.

References

  1. Schnabel RB, Yin X, Gona P, Larson MG, Beiser AS, McManus DD et al (2015) 50 year trends in atrial fibrillation prevalence, incidence, risk factors, and mortality in the Framingham Heart Study: a cohort study. Lancet 386(9989):154–162

    Article  PubMed  PubMed Central  Google Scholar 

  2. Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomström-Lundqvist C et al (2020) 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J 42(5):373–498

    Article  Google Scholar 

  3. Estes C, Anstee QM, Arias-Loste MT, Bantel H, Bellentani S, Caballeria J et al (2018) Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016–2030. J Hepatol 69(4):896–904

    Article  PubMed  Google Scholar 

  4. Abeysekera KWM, Fernandes GS, Hammerton G, Portal AJ, Gordon FH, Heron J et al (2020) Prevalence of steatosis and fibrosis in young adults in the UK: a population-based study. Lancet Gastroenterol Hepatol 5(3):295–305

    Article  PubMed  PubMed Central  Google Scholar 

  5. Lee H, Choi E-K, Rhee T-M, Lee S-R, Lim W-H, Kang S-H et al (2017) Cirrhosis is a risk factor for atrial fibrillation: a nationwide, population-based study. Liver Int 37(11):1660–1667

    Article  PubMed  Google Scholar 

  6. Huang WA, Dunipace EA, Sorg JM, Vaseghi M (2018) Liver disease as a predictor of new-onset atrial fibrillation. J Am Heart Assoc. https://doi.org/10.1161/JAHA.118.008703

    Article  PubMed  PubMed Central  Google Scholar 

  7. Käräjämäki AJ, Pätsi O-P, Savolainen M, Kesäniemi YA, Huikuri H, Ukkola O (2015) Non-alcoholic fatty liver disease as a predictor of atrial fibrillation in middle-aged population (OPERA Study). PLoS One 10(11):e0142937

    Article  PubMed  PubMed Central  Google Scholar 

  8. Park HE, Lee H, Choi S-Y, Kim HS, Chung GE (2020) The risk of atrial fibrillation in patients with non-alcoholic fatty liver disease and a high hepatic fibrosis index. Sci Rep. https://doi.org/10.1038/s41598-020-61750-4

    Article  PubMed  PubMed Central  Google Scholar 

  9. Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M et al (2018) The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology 67(1):328–357

    Article  PubMed  Google Scholar 

  10. Wai C (2003) A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology 38(2):518–526

    Article  PubMed  Google Scholar 

  11. Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J et al (2006) Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology 43(6):1317–1325

    Article  CAS  PubMed  Google Scholar 

  12. Raposeiras-Roubin S, Abu-Assi E, Marchán A, Fernández-Sanz T, Barreiro-Pardal C, Pousa IM et al (2022) Validation of embolic and bleeding risk scores in patients with atrial fibrillation and cancer. Am J Cardiol 180:44–51

    Article  PubMed  Google Scholar 

  13. McPherson S, Hardy T, Dufour JF, Petta S, Romero-Gomez M, Allison M et al (2017) Age as a confounding factor for the accurate non-invasive diagnosis of advanced NAFLD fibrosis. Am J Gastroenterol 112(5):740–751

    Article  PubMed  Google Scholar 

  14. Hicks KA, Mahaffey KW, Mehran R, Nissen SE, Wiviott SD, Dunn B et al (2018) 2017 Cardiovascular and stroke endpoint definitions for clinical trials. Circulation 137(9):961–972

    Article  PubMed  Google Scholar 

  15. Schulman S, Kearon C, Scientific Tsocoaot, Thrombosis Scotiso, Haemostasis (2005) Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 3(4):692–694

    Article  CAS  PubMed  Google Scholar 

  16. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA et al (2018) Fourth universal definition of myocardial infarction (2018). Eur Heart J 40(3):237–269

    Article  Google Scholar 

  17. Bozkurt B, Coats AJS, Tsutsui H, Abdelhamid CM, Adamopoulos S, Albert N et al (2021) Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure. Eur J Heart Fail 23(3):352–380

    Article  PubMed  Google Scholar 

  18. Ramakrishnan A, Velmurugan G, Somasundaram A, Mohanraj S, Vasudevan D, Vijayaragavan P et al (2022) Prevalence of abnormal liver tests and liver fibrosis among rural adults in low and middle-income country: a cross-sectional study. eClinicalMedicine 51:101553

    Article  PubMed  PubMed Central  Google Scholar 

  19. Saito Y, Okumura Y, Nagashima K, Fukamachi D, Yokoyama K, Matsumoto N et al (2020) Impact of the Fibrosis-4 index on risk stratification of cardiovascular events and mortality in patients with atrial fibrillation: findings from a Japanese Multicenter Registry. J Clin Med 9(2):584

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Qamar A, Vaduganathan M, Greenberger NJ, Giugliano RP (2018) Oral anticoagulation in patients with liver disease. J Am Coll Cardiol 71(19):2162–2175

    Article  CAS  PubMed  Google Scholar 

  21. Steffel J, Collins R, Antz M, Cornu P, Desteghe L, Haeusler KG et al (2021) 2021 European Heart Rhythm Association Practical Guide on the Use of Non-Vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Europace 23(10):1612–1676

    Article  PubMed  Google Scholar 

  22. Pastori D, Lip GYH, Farcomeni A, Del Sole F, Sciacqua A, Perticone F et al (2018) Incidence of bleeding in patients with atrial fibrillation and advanced liver fibrosis on treatment with vitamin K or non-vitamin K antagonist oral anticoagulants. Int J Cardiol 264:58–63

    Article  PubMed  Google Scholar 

  23. Xanthopoulos A, Starling RC, Kitai T, Triposkiadis F (2019) Heart failure and liver disease: cardiohepatic interactions. JACC Heart Fail 7(2):87–97

    Article  PubMed  Google Scholar 

  24. Nakashima M, Sakuragi S, Miyoshi T, Takayama S, Kawaguchi T, Kodera N et al (2021) Fibrosis-4 index reflects right ventricular function and prognosis in heart failure with preserved ejection fraction. ESC Heart Fail 8(3):2240–2247

    Article  PubMed  PubMed Central  Google Scholar 

  25. Soloveva A, Kobalava Z, Fudim M, Ambrosy AP, Villevalde S, Bayarsaikhan M et al (2019) Relationship of liver stiffness with congestion in patients presenting with acute decompensated heart failure. J Card Fail 25(3):176–187

    Article  PubMed  Google Scholar 

  26. Iwasaki Y, Tomiyama H, Shiina K, Matsumoto C, Kimura K, Fujii M et al (2018) Liver stiffness and arterial stiffness/abnormal central hemodynamics in the early stage of heart failure. Int J Cardiol Heart Vasc 20:32–37

    PubMed  PubMed Central  Google Scholar 

  27. Maeda D, Sakane K, Ito T, Kanzaki Y, Sohmiya K, Hoshiga M (2020) Fibrosis-4 index reflects right-sided filling pressure in patients with heart failure. Heart Vessels 35(3):376–383

    Article  PubMed  Google Scholar 

  28. Sato Y, Yoshihisa A, Kanno Y, Watanabe S, Yokokawa T, Abe S et al (2017) Liver stiffness assessed by Fibrosis-4 index predicts mortality in patients with heart failure. Open Heart 4(1):e000598

    Article  PubMed  PubMed Central  Google Scholar 

  29. Ahloulay M, Déchaux M, Hassler C, Bouby N, Bankir L (1996) Cyclic AMP is a hepatorenal link influencing natriuresis and contributing to glucagon-induced hyperfiltration in rats. J Clin Investig 98(10):2251–2258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Pais R, Redheuil A, Cluzel P, Ratziu V, Giral P (2019) Relationship among fatty liver, specific and multiple-site atherosclerosis, and 10-year framingham score. Hepatology 69(4):1453–1463

    Article  PubMed  Google Scholar 

  31. Lee YH, Kim KJ, Yoo ME, Kim G, Yoon HJ, Jo K et al (2018) Association of non-alcoholic steatohepatitis with subclinical myocardial dysfunction in non-cirrhotic patients. J Hepatol 68(4):764–772

    Article  PubMed  Google Scholar 

  32. van den Dries CJ, van Doorn S, Rutten FH, Oudega R, van de Leur S, Elvan A et al (2020) Integrated management of atrial fibrillation in primary care: results of the ALL-IN cluster randomized trial. Eur Heart J 41(30):2836–2844

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

None.

Author information

Authors and Affiliations

  1. Cardiology Department, University Hospital Álvaro Cunqueiro, Estrada de Clara Campoamor, 341, 36213, Vigo, Pontevedra, Spain

    Sergio Raposeiras-Roubín, Jose Antonio Parada Barcia, Andrea Lizancos Castro, Vanessa Noriega Caro, Ana Ledo Piñeiro, Inmaculada González Bermúdez, Rocío González Ferreiro, Andrés Íñiguez-Romo & Emad Abu-Assi

  2. Instituto de Investigación Sanitaria Galicia Sur, Vigo, Spain

    Sergio Raposeiras-Roubín, Jose Antonio Parada Barcia, Andrea Lizancos Castro, Vanessa Noriega Caro, Ana Ledo Piñeiro, Inmaculada González Bermúdez, Rocío González Ferreiro, Andrés Íñiguez-Romo & Emad Abu-Assi

  3. Faculty of Biomedical Engineering, Vigo University, Vigo, Spain

    Sergio Raposeiras-Roubín

  4. Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain

    Sergio Raposeiras-Roubín

Authors
  1. Sergio Raposeiras-Roubín
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jose Antonio Parada Barcia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrea Lizancos Castro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vanessa Noriega Caro
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ana Ledo Piñeiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Inmaculada González Bermúdez
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rocío González Ferreiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Andrés Íñiguez-Romo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Emad Abu-Assi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sergio Raposeiras-Roubín.

Ethics declarations

Conflict of interest

We declare no competing interests.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 340 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Raposeiras-Roubín, S., Parada Barcia, J.A., Lizancos Castro, A. et al. Liver fibrosis and outcomes of atrial fibrillation: the FIB-4 index. Clin Res Cardiol 113, 313–323 (2024). https://doi.org/10.1007/s00392-023-02330-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00392-023-02330-0

Keywords

Search

Navigation