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Open Access Highly Accessed Research article

Leflunomide increases the risk of silent liver fibrosis in patients with rheumatoid arthritis receiving methotrexate

Sang-Won Lee12, Hee-Jin Park12, Beom Kyung Kim145, Kwang-Hyub Han1345, Soo-Kon Lee123, Seung Up Kim145* and Yong-Beom Park123*

Author affiliations

1 Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu Seoul, 120-752, Korea

2 Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine,; 50 Yonsei-ro, Seodaemun-gu; Seoul, 120-752, Korea

3 Department of Medical Sciences, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu; Seoul, 120-752, Korea

4 Institute of Gastroenterology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu; Seoul, 120-752, Korea

5 Liver Cirrhosis Clinical Research Center, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu; Seoul, 120-752, Korea

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Citation and License

Arthritis Research & Therapy 2012, 14:R232  doi:10.1186/ar4075

Published: 29 October 2012

Abstract

Introduction

We identified silent liver fibrosis in patients with rheumatoid arthritis (RA) using transient elastography, and investigated medication that correlated with abnormal liver stiffness measurement (LSM) values.

Methods

We consecutively enrolled 105 patients with RA taking methotrexate over 24 weeks with normal liver functions and no history of underlying chronic liver disease. Blood tests were performed, and body mass index and metabolic syndrome were assessed. We checked LSM values, and adopted 5.3 kPa as the cutoff for abnormal LSM values. The cumulative doses of medications including methotrexate, leflunomide, sulfasalazine, hydroxychloroquine, prednisolone, meloxicam, and celecoxib were calculated.

Results

The median age of patients (20 men and 85 women) was 52.4 years. The median LSM value was 4.7 kPa and 24 (22.9%) patients had abnormal LSM values. Gamma-glutamyltranspeptidase levels and the cumulative doses of leflunomide and prednisolone significantly correlated with LSM values (P<0.05). The cumulative dose of leflunomide, but not methotrexate, was significantly higher in patients with abnormal LSM values than that in patients with normal LSM values (P = 0.008). When RA patients receiving leflunomide plus methotrexate were classified into two groups according to the optimal cutoff cumulative dose of leflunomide (19,170 mg), abnormal LSM values were more frequently identified in patients with high cumulative dose of leflunomide (odds ratio, 12.750; P<0.001).

Conclusions

The cumulative dose of leflunomide was the only independent predictor of abnormal LSM values in patients with RA who had received methotrexate for more than six months.