Evaluation of Liver Fibrosis by Shear Wave Elastography in Methotrexate-Treated Rheumatoid Arthritis Patients

Abstract

Background and Aim Methotrexate (MTX) is a widely used drug for treatment of rheumatoid arthritis (RA), and a concern with drug-related liver fibrosis is still an unsolved problem. Although liver biopsy is the gold standard for assessment of liver fibrosis, it has several limitations. A newly developed real-time shear wave elastography (SWE) is an accurate, risk-free, repeatable and reproducible technique to evaluate liver stiffness (LS), which accurately reflects liver fibrosis. The aims of this study are to investigate the prevalence of clinically significant liver fibrosis assessed by liver stiffness measurement (LSM) with SWE and to detect the associated factors in RA patients treated with MTX.

Materials and methods From August 2011 to February 2012, we prospectively analyzed a total of 173 patients (female 137, mean age 54.7 ± 9.4years) with RA who underwent SWE, blood tests and anthropometric measurement on the same day. The MTX cumulative dose and duration was also calculated. LSM by SWE is expressed in kilo-Pascal (kPa) with median value. Based on a previous study, significant liver fibrosis is defined as LSM equal to or more than 7.1 kPa.We analyzed the correlation between liver fibrosis using LSM value and MTX cumulative dose and duration, body mass index (BMI), hypertension, diabetes mellitus, white blood cells, hemoglobin, platelet, glucose, cholesterol, AST, ALT, total bilirubin, GGT, AST/platelet ratio index (APRI), and ultrasound-based fatty liver by univariate and multivariate analysis, using SPSS 18.0 Statistical Software.

Results Among 173 patients, 37 (21.4%) had LSM ≥7.1 kPa, suggesting significant fibrosis. In univariate analysis, BMI, hypertension, AST, glucose, and degree of ultrasound-based fatty liver were associated with liver stiffness (p<0.05). Neither MTX cumulative dose (4,840±3,430 mg vs. 4,817±3,090 mg, p=0.97) nor MTX treatment duration (329±202 weeks vs. 343±190 weeks, p=0.72) was associated with elevated LS. In multivariate analysis, only BMI (odds ratio 1.56, 95% CI, 1.30-1.87, p<0.001) and serum AST level (odds ratio 1.16, 95% CI, 1.04-1.29, p=0.006) were associated with significant liver stiffness.

Conclusion Significant liver fibrosis, defined as LSM ≥7.1 kPa, was detected in about 20% of patients with RA taking long-term MTX, and it was associated with only BMI and serum AST levels, but not with MTX cumulative dose and treatment duration. Rather than MTX, other factors such as BMI, obesity or other co-morbidity might have a role in liver toxicity and fibrosis in patients with RA.