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Methotrexate does not increase the risk of liver fibrosis in patients with rheumatoid arthritis: assessment by ultrasound elastography (ARFI-MetRA study)



Only limited data are available on the risk of liver fibrosis in patients with rheumatoid arthritis on long-term methotrexate treatment. To assess the risk of liver fibrosis in patients with rheumatoid arthritis treated with methotrexate, non-invasive, ultrasound-based elastography [acoustic radiation force impulse (ARFI) imaging] was applied.


In total, 119 patients were assessed using acoustic radiation force impulse (ARFI) imaging between July 2018 and April 2019. In a cross-sectional, single-centre study design, ARFI scores were compared between patient subgroups with (n = 65) and without (n = 54) methotrexate exposure. The main outcome variable was the mean fibrosis score as measured by the ARFI method. The mean shear wave velocity was calculated from 10 valid ARFI measurements for each patient. Inferential statistical analyses (between group) were performed using ANOVA for independent samples in the case of continuous outcome variables.


Sixty-five patients with and fifty-four patients without MTX exposure were assessed using the ARFI elastography method. Participating patients on MTX medication (1.113 m/s) showed ARFI scores that were comparable to those of participants without MTX exposure (1.062 m/s); P = 0.228. The mean cumulative dose in the group of MTX-exposed patients was 3602 mg.


The mean value of the repeated determination of liver density using ARFI imaging did not differ significantly between the MTX-exposed and MTX-naive patients with RA. No increased rate of liver fibrosis was found among RA patients treated with MTX.

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Data availability

The data underlying this article will be shared upon reasonable request to the corresponding author.

Code availability

Data management and statistical analyses were performed for all data as appropriate using Microsoft Excel or SPSS (German version 17.0.0) software, respectively.


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No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article.

Author information




MF: concept and design; patient recruitment; data management; ethics; statistics; writing of the article. LK: carried out the measurements; data management; statistics; writing of the article. AS: data management; statistics; writing of the article. AN: patient recruitment; data management. HSK: concept and design; statistics; writing of the article.

Corresponding author

Correspondence to Martin Feuchtenberger.

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Conflict of interest

Dr. Feuchtenberger reports personal fees from AbbVie, personal fees from Roche, personal fees from UCB, outside the submitted work. Dr. Kraus has nothing to disclose. Dr. Schäfer reports personal fees from Novo Nordisk Pharma GmbH, outside the submitted work. Dr. Nigg has nothing to disclose. Dr. Schulze-Koops has nothing to disclose.

Ethics approval

The observational study was approved by the ethics committee of the University of Würzburg, Germany, on 12 July 2018.

Informed consent

All patients provided written informed consent for liver elastometry measurements, study participation and publication of data.

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The revised paper has been read and approved by all authors.

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Feuchtenberger, M., Kraus, L., Nigg, A. et al. Methotrexate does not increase the risk of liver fibrosis in patients with rheumatoid arthritis: assessment by ultrasound elastography (ARFI-MetRA study). Rheumatol Int 41, 1079–1087 (2021).

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  • Methotrexate
  • Rheumatoid arthritis
  • Fibrosis
  • Liver
  • Acoustic radiation force impulse
  • ARFI