Observational Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
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

Methotrexate (MTX) is the usual first-line treatment for rheumatoid arthritis (RA). Long-term use of MTX has been associated with liver steatosis (LS) and liver fibrosis (LF).


To determine if LS in patients treated with MTX for RA is associated with MTX cumulative dose (MTX-CD), metabolic syndrome (MtS), body mass index (BMI), the male sex, or LF.


A single-center, prospective study of patients receiving MTX for RA was performed from February 2019 to February 2020. The inclusion criteria were patients aged 18 years or older diagnosed with RA by a rheumatologist and being treated with MTX (without limitation on the duration of treatment). The exclusion criteria were previous diagnosis of liver disease (hepatitis B or C virus infection, known nonalcoholic fatty liver disease), alcohol consumption greater than 60 g/d in males or 40 g/d in females, human immunodeficiency virus infection on antiretroviral therapy, diabetes mellitus, chronic renal failure, congestive heart failure, or BMI greater than 30 kg/m². Patients receiving leflunomide in the 3 years prior to the study were also excluded. Transient elastography (FibroScan, Echosens®, Paris, France) was used for fibrosis determination (LF > 7 KpA) and computer attenuation parameter (CAP) for LS (CAP > 248 dB/m). Demographic variables, laboratory data, MTX-CD (> 4000 mg), MtS criteria, BMI (> 25), transient elastography, and CAP scores were collected from all patients.


Fifty-nine patients were included. Forty-three were female (72.88%), and the mean age was 61.52 years (standard deviation: 11.73). When we compared MTX-CD ≤ 4000 mg (26 patients; 14 with LS and 12 without) with > 4000 mg (33 patients; 12 with LS and 21 without), no statistical differences were found (P = 0.179). We compared CAP scores stratified by MtS, BMI, sex, and LF. There were no significant differences in CAP scores based on the presence of MtS [CAP/MtS: 50 no MtS (84.75%); 9 MtS (15.25%); P = 0.138], the male sex (CAP/sex: 8 male/18 female LS; 8 male/25 female no LS; P = 0.576), or LF [CAP/fibrosis: 53 no LF (89.83%); 6 LF (10.17%); P = 0.239]. LS determined by CAP was significantly associated with BMI > 25 (CAP/BMI: 22 BMI ≤ 25 (37.29%); 37 BMI > 25 (62.71%); P = 0.002].


LS in patients with RA treated with MTX was not associated with MTX-CD, LF, the male sex, or MtS. However, BMI was significantly related to LS in these patients.

Keywords: Methotrexate, Rheumatoid arthritis, Liver steatosis, Liver fibrosis, Transient elastography, Computed attenuation parameter

Core Tip: Methotrexate (MTX) is the cornerstone of treatment for rheumatoid arthritis and has been associated with the development of liver fibrosis (LF) and liver steatosis (LS). The objective of this work was to study if LS in patients with rheumatoid arthritis treated with MTX and determine the association with body mass index, MTX cumulative dose, sex, LF, and metabolic syndrome. We concluded that LS in patients with rheumatoid arthritis on MTX treatment was not related to MTX-cumulative dose, LF, the male sex, or metabolic syndrome. In our study, body mass index was significantly associated with LS in these patients.