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Methotrexate use does not increase the prevalence of hepatic steatosis: a real-world retrospective nested case-control study

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Abstract

Objective

We aimed to determine whether methotrexate (MTX) treatment in patients with rheumatoid arthritis (RA) leads to the development of non-alcoholic fatty liver (NAFL).

Method

Data were derived from records of all patients with RA who underwent abdominal ultrasonography at the Jeonbuk National University Hospital. Patients with ultrasound-proven NAFL were identified, and those without NAFL were matched by age and sex using the propensity score matching method at 1:3 ratio. We also analyzed the Health Insurance Review and Assessment Service-National Patient Samples, a nationwide cohort database, to determine the association between MTX use and NAFL in a large number of patients (n = 24,653).

Results

In the hospital cohort, 92 patients with NAFL did not show significant differences in the cumulative MTX dose when compared with the no-NAFL group (n = 276) (1908.5 ± 1757.5 vs. 1948.6 ± 2118.8 mg, p = 0.911). The prevalence of NAFL was not significantly different across strata of cumulative MTX dose. Multiple logistic analyses identified hypertriglyceridemia (OR, 4.88 [95% CI, 1.13–20.93]) and higher body mass index (OR, 1.22 [95% CI, 1.05–1.41]) as being associated with an increased risk of NAFL. In the nationwide cohort, the MTX exposure rate between the NAFL and no-NAFL groups was not significantly different.

Conclusions

Collectively, no significant association between NAFL development and administration of MTX was detected in this study. Our results suggest that it is more efficient to adjust for individualized risk factors for NAFL prevention rather than discontinuation of MTX in patients with RA.

Key Points

• NAFLD has been highlighted with increasing prevalence worldwide and possible progression to end-stage liver disease.

• Cumulative dose or exposure history of MTX does not show a significant association with NAFLD prevalence.

• Modifying well-established risk factors is more efficient in NAFLD prevention rather than discontinuation of MTX.

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Acknowledgments

We would like to thank Editage (www.editage.co.kr) for English language editing.

Funding

This paper was supported by Fund of Biomedical Research Institute, Jeonbuk National University Hospital.

Author information

Author notes

  1. Yunjung Choi and Chang Hun Lee contributed equally to this work.

Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Jeonbuk National University Hospital, Jeonju, South Korea

    Yunjung Choi & Wan-Hee Yoo

  2. Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, South Korea

    Yunjung Choi, Chang Hun Lee, In Hee Kim, Eun Hae Park & Wan-Hee Yoo

  3. Division of Gastroenterology, Department of Internal Medicine, Jeonbuk National University Hospital, Jeonju, South Korea

    Chang Hun Lee & In Hee Kim

  4. Department of Radiology, Jeonbuk National University Hospital, Jeonju, South Korea

    Eun Hae Park

  5. Data Science Team, Hanmi Pharm. Co., Ltd, Seoul, South Korea

    SoJeong Park

Authors
  1. Yunjung Choi
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  2. Chang Hun Lee
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Contributions

Y.J.C and C.H.L made contributions to the conception or design of the work; C.H.L., Y.J.C, and S.J.P collected and analyzed the data; E.H.P reviewed and confirmed the ultrasound results; C.H.L., Y.J.C., S.J.P, and I.H.K. drafted the manuscript; C.H.L., Y.J.C, I.H.K, and W.H.Y revised the manuscript; I.H.K. and W.H.Y supervised the study; all authors reviewed the manuscript.

Corresponding author

Correspondence to Wan-Hee Yoo.

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Ethics approval

This study was performed in accordance with the ethical standards of 1964 Helsinki declaration and approved by the Institutional Review Board of Jeonbuk National University Hospital, Jeonju, South Korea (CUH 2020-03-023-002)

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Choi, Y., Lee, C.H., Kim, I.H. et al. Methotrexate use does not increase the prevalence of hepatic steatosis: a real-world retrospective nested case-control study. Clin Rheumatol 40, 2037–2045 (2021). https://doi.org/10.1007/s10067-020-05456-y

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  • DOI: https://doi.org/10.1007/s10067-020-05456-y

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