Liver steatosis in patients with rheumatoid arthritis treated with methotrexate is associated with body mass index

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.