Abstract

BackgroundMethotrexate (MTX) is recommended as a first-line disease-modifying antirheumatic drug for treating rheumatoid arthritis (RA) in monotherapy or combinational therapy. A concern about MTX-related liver fibrosis in patients with rheumatoid arthritis (RA) is still unsolved.ObjectivesThe aim of the study cutoff of cumulative dose discriminating patients with normal from those with abnormal liver stiffness.MethodsWe conducted a cross-sectional study including consecutive RA patients diagnosed according 2009 ACR-EULAR criteria. Liver stiffness (LS) was assessed by Fibroscan in the gastroenterology department by an experienced operator.The LS is measured in kilopascals (kPa). It is normal when < 6.2 kPa. Above this rate it is considered pathological. Substantial liver fibrosis was defined as liver stiffness of greater than 8 kPa.We collected the following parameters: age, disease duration, disease activity assessed by DAS28, cumulated dose of MTX and duration of this treatment, and the body mass index (BMI). Patients underwent blood testing exploring hepatic function: alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl tansferase (GGT), total bilirubin (TB), albumin (ALB) and prothrombin time (PT).Statistical analysis was performed using SPSS software.ResultsThere were 18 men and 36 women. The mean age was 51.9 + 11.49 [22-83]. The mean BMI was 27.27 + 3.40. The mean disease duration 8.08 + 6.28 years. The mean DAS28CRP was 3.96 + 1.49.The mean cumulative dose of MTX was 3670 + 3432.61mg and mean MTX duration was 55.75 + 50.89 months. The mean of LS was 4.6 + 1.64 kPa.The means of the liver blood tests are as follows: AST 20.83 + 8.58 UI/L, ALT 19.60 + 9.39 UI/L, ALP 84.65 + 38.68UI/L, TB 9.50 + 4.79 UI/L, GGT 25.88 + 14.26UI/L, ALB 35.19 + 5.47 g/L, PT 94.60 + 9.02.Eight patients had abnormal LS values and two patients had advanced liver fibrosis. However, hepatic blood tests (AST, ALT, GGT, TB, ALB, PT) were normal in these patients.A correlation was found between LS and following parameters: cumulative dose of MTX (r: 0.347, p: 0.013), the methotrexate duration (r: 0.363, p: 0.010) and total bilirubin rate (r:0.390, p: 0.005).Receiver Operator Curve (ROC) analysis showed the cutoff point of cumulative dose of MTX with the best accuracy in distinguishing patients with normal LS from those with LS higher than 6.2 kPA was 7330 mg, with a sensitivity of 50% and specificity of 91.3% (air under the curve (AUC) value: 0.732 (p=0.03).ConclusionOur study showed that LS correlated to both MTX duration and cumulative dose. Patients with a cumulative dose of MTX higher than 7330 mg required a close follow up of liver elastometry and monitoring of hepatic function.Disclosure of InterestsNone declared

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