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

BACKGROUND: 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). AIM: 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. METHODS: 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. RESULTS: 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]. CONCLUSION: 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.