Observational Study
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World J Hepatol. May 27, 2023; 15(5): 699-706
Published online May 27, 2023. doi: 10.4254/wjh.v15.i5.699
Liver steatosis in patients with rheumatoid arthritis treated with methotrexate is associated with body mass index
Agustin Castiella, Luis Lopez-Dominguez, Maria J Sanchez-Iturri, Iratxe Urreta, Andrea De Diego, Joaquin Belzunegui, Eva Zapata
Agustin Castiella, Department of Gastroenterology Service, Donostia University Hospital, Donostia 20014, Spain
Luis Lopez-Dominguez, Andrea De Diego, Joaquin Belzunegui, Department of Rheumatology, Donostia University Hospital, Donostia 20014, Spain
Maria J Sanchez-Iturri, Eva Zapata, Department of Gastroenterology, Donostia University Hospital, Donostia 20014, Spain
Iratxe Urreta, Department of Clinical Epidemiology, Donostia University Hospital, Donostia 20014, Spain
Author contributions: Castiella A and Lopez-Dominguez L were the guarantors and designed the study; Castiella A, Lopez-Dominguez L, Sanchez-Iturri MJ, Urreta I, De Diego A, Belzunegui J, and Zapata E participated in the acquisition, analysis, and interpretation of the data and drafted the initial manuscript; Castiella A, Lopez-Dominguez L, and Zapata E revised the article critically for important intellectual content.
Institutional review board statement: Institutional review board statement statement: The study was reviewed and approved by the clinical research ethics committee of the Gipuzkoa health area (Código de Protocolo: ACLFSC-2018-01; Acta 01/2019).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All authors report having no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement checklist of items, and the manuscript was prepared and revised according to the STROBE Statement checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Agustin Castiella, MD, PhD, Staff Physician, Department of Gastroenterology Service, Donostia University Hospital, Servicio Digestivo, Donostia 20014, Spain. agustincastiella@yahoo.es
Received: December 16, 2022
Peer-review started: December 16, 2022
First decision: December 31, 2022
Revised: January 7, 2023
Accepted: April 10, 2023
Article in press: April 10, 2023
Published online: May 27, 2023
Processing time: 158 Days and 11.8 Hours
ARTICLE HIGHLIGHTS
Research background

Methotrexate (MTX) remains the cornerstone of treatment for rheumatoid arthritis (RA), both in monotherapy and in association with other treatments. The most concerning adverse effect of this treatment, in the long term, is liver fibrosis (LF). Liver steatosis (LS) has been associated with RA and with MTX.

Research motivation

MTX, as a risk factor for secondary LS, has been studied recently. RA has been independently associated with moderate to severe LS. Sex, higher body mass index (BMI), and MTX cumulative dose (MTX-CD) are predisposing factors. However, the studies have shown conflicting results, and the impact of MTX on LS is still unclear.

Research objectives

The objective of our work was to study if LS in RA patients treated with MTX was related to BMI, MTX-CD, metabolic syndrome (MtS), sex, or LF.

Research methods

We performed a prospective study of RA patients treated with MTX. The principal objective of this work was to study the presence of LF by transient elastography and aspartate aminotransferase to platelet ratio index as well as the detection of LS by ultrasonography and computer attenuation parameter (CAP).

Research results

Fifty-nine patients were included in the study. When comparing MTX-CD ≤ 4000 mg with > 4000 mg, we found no statistical differences in LS between low and high MTX-CD. We compared CAP scores with MtS, BMI, sex, and LF. There were no significant differences based on the presence or absence of MtS, the male sex, or LF. LS determined by CAP was significantly associated with BMI > 25.

Research conclusions

We concluded that, in our series, LS in RA patients treated with MTX is not related to sex, MTX-CD, MtS, or LF. BMI > 25 is significatively associated with LS in our study. Other factors, apart from MTX-CD or time in treatment, are more important for the development of LS in these patients.

Research perspectives

The routine incorporation of FS for the study of LF and LS in RA patients with MTX treatment is critical and will aid in understanding the real impact of MTX on LS. More studies (larger and multicentric) are recommended to validate these results.