Skip to main content

Advertisement

SpringerLink
Log in

Prevalence of Steatotic Liver Disease Among US Adults with Rheumatoid Arthritis

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

The prevalence of steatotic liver disease (SLD) among patients with rheumatoid arthritis (RA) remains largely unknown.

Aims

To investigate the prevalence of SLD and liver fibrosis among patients with RA.

Methods

We utilized data from the United States (US)-based National Health and Nutrition Examination Survey (NHANES) 2017–2020 cycle. After applying established sample weights, we estimated the age-adjusted prevalence of SLD and its subclassifications (CAP ≥ 285 dB/m), high-risk NASH (FAST score) and liver fibrosis (LSM) among participants with self-reported RA. Multivariable logistic regression was performed to identify independent risk factors for metabolic dysfunction associated SLD (MASLD), high-risk NASH and fibrosis, respectively, among participants with RA. We present adjusted odds ratios (aORs) and 95% confidence intervals (CIs).

Results

Age-adjusted prevalence of MASLD among US adults with RA was 34.91% (95% CI: 24.02–47.65%). We also found that the age-adjusted prevalence of high-risk NASH (FAST score > 0.35) and significant fibrosis (LSM > 8.6 kPa) was 12.97% (95% CI: 6.89–23.07%) and 10.35% (95% CI: 5.55–18.48%), respectively. BMI ≥ 30 kg/m2, (aOR 6.23; 95% CI: 1.95–19.88), diabetes (aOR 5.90; 95% CI: 1.94–17.94), and dyslipidemia (aOR 2.83; 95% CI: 1.12–7.11) were independently associated with higher odds of MASLD among participants with RA. Diabetes (aOR 19.34; 95% CI: 4.69–79.70) was also independently associated with high-risk NASH.

Conclusions

The prevalence of MASLD, high-risk NASH, and liver fibrosis among patients with RA is equal or higher than the general population. Future studies of large cohorts are needed to substantiate the role of systemic inflammation in the pathophysiology of MASLD.

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

Similar content being viewed by others

Abbreviations

ALD:

Alcohol-associated liver disease

aOR:

Adjusted odds ratio

AST:

Aspartate aminotransferase

BMI:

Body mass index

CAP:

Controlled attenuation parameter

CI:

Confidence interval

DMARDs:

Disease-modifying anti-rheumatic drugs

FAST:

FibroScan-AST

HBsAg:

Hepatitis B virus surface antigen

HCV:

Hepatitis C virus

IL:

Interleukin

IQR:

Interquartile range

JAKi:

Janus kinase inhibitor

LSM:

Liver stiffness measurements

MASLD:

Metabolic dysfunction associated steatotic liver disease

MASH:

Metabolic dysfunction associated steatohepatitis

MetALD:

MASLD and increased alcohol intake

NAFLD:

Non-alcoholic fatty liver disease

NASH:

Non-alcoholic steatohepatitis

NH:

Non-Hispanic

NHANES:

Nutrition Examination Survey

RA:

Rheumatoid arthritis

SLD:

Steatotic liver disease

TNF:

Tumor necrosis factor

US:

United States

VCTE:

Vibration controlled transient elastography

References

  1. Rinella ME, Lazarus JV, Ratziu V, et al. A multi-society Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol. 2023.

  2. Younossi ZM, Koenig AB, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73–84.

    Article  PubMed  Google Scholar 

  3. Hagström H, Vessby J, Ekstedt M, et al. 99% of patients with NAFLD meet MASLD criteria and natural history is therefore identical. J Hepatol. 2023.

  4. Buzzetti E, Pinzani M, Tsochatzis EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism. 2016;65(8):1038–48.

    Article  CAS  PubMed  Google Scholar 

  5. Bugianesi E, McCullough AJ, Marchesini G. Insulin resistance: a metabolic pathway to chronic liver disease. Hepatology. 2005;42(5):987–1000.

    Article  CAS  PubMed  Google Scholar 

  6. Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD practice guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023.

  7. Ciardullo S, Carbone M, Invernizzi P, et al. Exploring the landscape of steatotic liver disease in the general US population. Liver Int. 2023.

  8. Eddowes PJ, Sasso M, Allison M, et al. Accuracy of FibroScan Controlled Attenuation Parameter and Liver Stiffness Measurement in Assessing Steatosis and Fibrosis in Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology. 2019;156(6):1717–30.

    Article  PubMed  Google Scholar 

  9. Siddiqui MS, Vuppalanchi R, Van Natta ML, et al. Vibration-Controlled Transient Elastography to Assess Fibrosis and Steatosis in Patients With Nonalcoholic Fatty Liver Disease. Clin Gastroenterol Hepatol. 2019;17(1):156 – 63.e2.

    Article  PubMed  Google Scholar 

  10. Newsome PN, Sasso M, Deeks JJ, et al. FibroScan-AST (FAST) score for the non-invasive identification of patients with non-alcoholic steatohepatitis with significant activity and fibrosis: a prospective derivation and global validation study. Lancet Gastroenterol Hepatol. 2020;5(4):362–73.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Yki-Järvinen H. Non-alcoholic fatty liver disease as a cause and a consequence of metabolic syndrome. Lancet Diabetes Endocrinol. 2014;2(11):901–10.

    Article  PubMed  Google Scholar 

  12. Friedman SL, Neuschwander-Tetri BA, Rinella M, et al. Mechanisms of NAFLD development and therapeutic strategies. Nat Med. 2018;24(7):908–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Trépo E, Valenti L. Update on NAFLD genetics: From new variants to the clinic. J Hepatol. 2020;72(6):1196–209.

    Article  PubMed  Google Scholar 

  14. Sutti S, Albano E. Adaptive immunity: an emerging player in the progression of NAFLD. Nat Rev Gastroenterol Hepatol. 2020;17(2):81–92.

    Article  CAS  PubMed  Google Scholar 

  15. Arrese M, Cabrera D, Kalergis AM, et al. Innate Immunity and Inflammation in NAFLD/NASH. Dig Dis Sci. 2016;61(5):1294–303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Bruzzì S, Sutti S, Giudici G, et al. B2-Lymphocyte responses to oxidative stress-derived antigens contribute to the evolution of nonalcoholic fatty liver disease (NAFLD). Free Radic Biol Med. 2018;124:249–59.

    Article  PubMed  Google Scholar 

  17. Smallwood MJ, Nissim A, Knight AR, et al. Oxidative stress in autoimmune rheumatic diseases. Free Radic Biol Med. 2018;125:3–14.

    Article  CAS  PubMed  Google Scholar 

  18. Gravallese EM, Firestein GS. Rheumatoid Arthritis - Common Origins, Divergent Mechanisms. N Engl J Med. 2023;388(6):529–42.

    Article  CAS  PubMed  Google Scholar 

  19. Curtis JR, Beukelman T, Onofrei A, et al. Elevated liver enzyme tests among patients with rheumatoid arthritis or psoriatic arthritis treated with methotrexate and/or leflunomide. Ann Rheum Dis. 2010;69(1):43–7.

    Article  CAS  PubMed  Google Scholar 

  20. Langman G, Hall PM, Todd G. Role of non-alcoholic steatohepatitis in methotrexate-induced liver injury. J Gastroenterol Hepatol. 2001;16(12):1395–401.

    Article  CAS  PubMed  Google Scholar 

  21. Lettéron P, Brahimi-Bourouina N, Robin MA, et al. Glucocorticoids inhibit mitochondrial matrix acyl-CoA dehydrogenases and fatty acid beta-oxidation. Am J Physiol. 1997;272(5 Pt 1):G1141-50.

    PubMed  Google Scholar 

  22. Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2021;73(7):1108–23.

    Article  PubMed  Google Scholar 

  23. Ruan Z, Lu T, Chen Y, et al. Association Between Psoriasis and Nonalcoholic Fatty Liver Disease Among Outpatient US Adults. JAMA Dermatol. 2022;158(7):745–53.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Roberts KK, Cochet AE, Lamb PB, et al. The prevalence of NAFLD and NASH among patients with psoriasis in a tertiary care dermatology and rheumatology clinic. Aliment Pharmacol Ther. 2015;41(3):293–300.

    Article  CAS  PubMed  Google Scholar 

  25. Miele L, Vallone S, Cefalo C, et al. Prevalence, characteristics and severity of non-alcoholic fatty liver disease in patients with chronic plaque psoriasis. J Hepatol. 2009;51(4):778–86.

    Article  CAS  PubMed  Google Scholar 

  26. Zamani M, Alizadeh-Tabari S, Chitkara P, et al. Prevalence of Nonalcoholic Fatty Liver Disease in Patients With Rheumatoid Arthritis: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2023;21(11):2789–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Centers for Disease Control and Prevention (CDC). National Center for Health Statistics (NCHS). National Health and Nutrition Examination Survey Data. Hyattsville, MD: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention 2017–2020 [Available from: https://www.cdc.gov/nchs/nhanes/index.htm.

  28. Stierman B, Afful J, Carroll MD, et al. National Health and Nutrition Examination Survey 2017–March 2020 Prepandemic Data Files Development of Files and Prevalence Estimates for Selected Health Outcomes. National Health Statistics Reports. 2021; NHSR No. 158.

  29. Peeters GM, Alshurafa M, Schaap L, et al. Diagnostic accuracy of self-reported arthritis in the general adult population is acceptable. J Clin Epidemiol. 2015;68(4):452–9.

    Article  PubMed  Google Scholar 

  30. Klein RJ, Schoenborn CA. Age adjustment using the 2000 projected U.S. population. Healthy People 2000 Stat Notes. 2001(20):1–9.

  31. Smolen JS, Landewé RBM, Bergstra SA, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023;82(1):3–18.

    Article  CAS  PubMed  Google Scholar 

  32. Ursini F, Russo E, Mauro D, et al. Complement C3 and fatty liver disease in Rheumatoid arthritis patients: a cross-sectional study. Eur J Clin Invest. 2017;47(10):728–35.

    Article  CAS  PubMed  Google Scholar 

  33. Erre GL, Castagna F, Sauchella A, et al. Prevalence and risk factors of moderate to severe hepatic steatosis in patients with rheumatoid arthritis: an ultrasonography cross-sectional case-control study. Ther Adv Musculoskelet Dis. 2021;13:1759720x211042739.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Cervoni JP, Alby-Lepresle B, Weil D, et al. A pragmatic non-invasive assessment of liver fibrosis in patients with psoriasis, rheumatoid arthritis or Crohn’s disease receiving methotrexate therapy. Clin Res Hepatol Gastroenterol. 2020;44s:100003.

    Article  PubMed  Google Scholar 

  35. Barbarroja N, Ruiz-Ponce M, Cuesta-López L, et al. Nonalcoholic fatty liver disease in inflammatory arthritis: Relationship with cardiovascular risk. Front Immunol. 2022;13:997270.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Androutsakos T, Voulgaris TA, Bakasis AD, et al. Liver Fibrosis in Primary Sjögren’s Syndrome. Front Immunol. 2022;13:889021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Mori S, Arima N, Ito M, et al. Non-alcoholic steatohepatitis-like pattern in liver biopsy of rheumatoid arthritis patients with persistent transaminitis during low-dose methotrexate treatment. PLoS One. 2018;13(8):e0203084.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Haukeland JW, Damås JK, Konopski Z, et al. Systemic inflammation in nonalcoholic fatty liver disease is characterized by elevated levels of CCL2. J Hepatol. 2006;44(6):1167–74.

    Article  CAS  PubMed  Google Scholar 

  39. Kerekes G, Nurmohamed MT, González-Gay MA, et al. Rheumatoid arthritis and metabolic syndrome. Nat Rev Rheumatol. 2014;10(11):691–6.

    Article  CAS  PubMed  Google Scholar 

  40. Zhang J, Fu L, Shi J, et al. The risk of metabolic syndrome in patients with rheumatoid arthritis: a meta-analysis of observational studies. PLoS One. 2013;8(10):e78151.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Ogresta D, Mrzljak A, Cigrovski Berkovic M, et al. Coagulation and Endothelial Dysfunction Associated with NAFLD: Current Status and Therapeutic Implications. J Clin Transl Hepatol. 2022;10(2):339–55.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Nasiri-Ansari N, Androutsakos T, Flessa CM, et al. Endothelial Cell Dysfunction and Nonalcoholic Fatty Liver Disease (NAFLD): A Concise Review. Cells. 2022;11(16).

    Article  Google Scholar 

  43. Vilar-Gomez E, Vuppalanchi R, Mladenovic A, et al. Prevalence of High-risk Nonalcoholic Steatohepatitis (NASH) in the United States: Results From NHANES 2017–2018. Clin Gastroenterol Hepatol. 2023;21(1):115 – 24.e7.

    Article  PubMed  Google Scholar 

  44. Di Martino V. Methotrexate-induced liver fibrosis: The end of a long-held belief. J Hepatol. 2023;78(5):896–7.

    Article  PubMed  Google Scholar 

  45. Choi Y, Lee CH, Kim IH, et al. Methotrexate use does not increase the prevalence of hepatic steatosis: a real-world retrospective nested case-control study. Clin Rheumatol. 2021;40(5):2037–45.

    Article  PubMed  Google Scholar 

  46. Cheema HI, Haselow D, Dranoff JA. Review of existing evidence demonstrates that methotrexate does not cause liver fibrosis. J Investig Med. 2022;70(7):1452–60.

    Article  PubMed  Google Scholar 

  47. Le MH, Yeo YH, Cheung R, et al. Ethnic influence on nonalcoholic fatty liver disease prevalence and lack of disease awareness in the United States, 2011–2016. J Intern Med. 2020;287(6):711–22.

    Article  CAS  PubMed  Google Scholar 

  48. Papatheodoridi AM, Chrysavgis L, Koutsilieris M, et al. The Role of Senescence in the Development of Nonalcoholic Fatty Liver Disease and Progression to Nonalcoholic Steatohepatitis. Hepatology. 2020;71(1):363–74.

    Article  CAS  PubMed  Google Scholar 

  49. Bauer ME. Accelerated immunosenescence in rheumatoid arthritis: impact on clinical progression. Immun Ageing. 2020;17:6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Brunt EM, Kleiner DE, Carpenter DH, et al. NAFLD: Reporting Histologic Findings in Clinical Practice. Hepatology. 2021;73(5):2028–38.

    Article  PubMed  Google Scholar 

  51. Nemes S, Jonasson JM, Genell A, et al. Bias in odds ratios by logistic regression modelling and sample size. BMC Med Res Methodol. 2009;9:56.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

Visual abstract was created with BioRender.com.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Author notes

  1. Athanasios Vassilopoulos and Markos Kalligeros contributed equally to this work.

Authors and Affiliations

  1. Division of Internal Medicine, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI, USA

    Athanasios Vassilopoulos, Markos Kalligeros, Stephanos Vassilopoulos, Gregorio Benitez, Matthew Kaczynski & Ingrid Lazaridou

  2. Houston Methodist Research Institute, Houston, TX, USA

    Fadi Shehadeh

  3. Department of Electrical and Computer Engineering, National Technical University of Athens, Athens, Greece

    Fadi Shehadeh

  4. Division of Gastroenterology and Hepatology, Providence VA Medical Center, Providence, RI, USA

    Kittichai Promrat

  5. Liver Research Center, The Warren Alpert Medical School of Brown University, Providence, RI, USA

    Jack R Wands

  6. Department of Medicine, Houston Methodist Hospital, Smith Tower 1001, Fannin, Houston, TX, 6550, 77030, USA

    Eleftherios Mylonakis

Authors
  1. Athanasios Vassilopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Markos Kalligeros
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stephanos Vassilopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fadi Shehadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gregorio Benitez
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Matthew Kaczynski
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ingrid Lazaridou
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kittichai Promrat
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jack R Wands
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Eleftherios Mylonakis
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

AV, MK, SV, FS, GB, MK, IL, KP, JRW and EM conceptualized and designed the study, and participated in data interpretation. AV, MK and FS prepared tables and figures and performed the statistical analysis. AV and MK drafted the initial manuscript. SV, FS, GB, MK, IL, KP, JRW and EM reviewed and revised the manuscript. All authors read and approved the final manuscript as submitted and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Eleftherios Mylonakis.

Ethics declarations

Conflicts of interest

SV, MK, AV, FS, IL, GB, MK, KP, JRW, EM have no conflicts of interest to declare.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

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

Vassilopoulos, A., Kalligeros, M., Vassilopoulos, S. et al. Prevalence of Steatotic Liver Disease Among US Adults with Rheumatoid Arthritis. Dig Dis Sci 69, 989–1003 (2024). https://doi.org/10.1007/s10620-023-08225-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-023-08225-4

Keywords

Search

Navigation