EVALUATION OF LIVER FIBROSIS IN PATIENTS WITH RHEUMATOID ARTHRITIS UNDER METHOTREXATE TREATMENT. UTILITY OF FIBROSCAN AND BIOMARKERS IN ROUTINE CLINICAL PRACTICE.

Background:Despite therapeutic advances in recent years, methotrexate (MTX) remains the gold standard for the treatment of rheumatoid arthritis (RA). Among the side effects that have been blamed on it are liver fibrosis (LF) and cirrhosis, although late studies have failed to show such a relation1,2. The only validated test in the diagnosis of LF is biopsy. Given the relevance of MTX in the treatment of RA, it is important to evaluate non-invasive diagnostic options for LF such as transitional elastography (FibroScan, FS).Objectives:To evaluate the percentage of LF in RA patients treated with MTX. Secondly, to assess the correlation between altered liver function, RA activity, and LF. To determine whether dose and/or duration of treatment with MTX may affect the development of LF in such patients.Methods:We did a prospective study between February 2019 and January 2020. Patients affected of RA treated with MTX were included. Patients with basal liver disease (hepatitis B, hepatitis C and steatohepatitis), alcohol consumption, type I diabetes mellitus, chronic renal failure, heart failure, obesity and concomitant treatment with leflunomide or antiretrovirals were excluded. Demographic, clinical, analytical and therapeutic variables were collected. Liver fibrosis was assessed by FS in kilopascals (kpa) and using the APRI score. RA activity was assessed by DAS28 score. Continuous variables are described with mean and standard deviation (SD), and qualitative variables are shown with absolute value and percentage. Spearman’s and Mann-Whitney’s U tests were used for the bivariate analysis.Results:Fifty patients were included (Table 1 and 2). Of these, 38 were women (76%) with mean age of 61.8 years (SD 11.7) and mean RA evolution time of 13.7 years (SD 8.2). The mean DAS28 at the visit was 2.39 (SD 1.1). The FS showed an average of 4.8 kpa (SD 2). The mean duration of treatment with MTX was 85.8 months (SD 93.3) and that of AD-MTX was 5414.6mg (SD 5011). Patients were divided into those with DA-MTX greater than 4000mg (21, 42%) and less than 4000mg (29, 58%) and no significant differences were found in terms of LF in FS (p 0.637) or APRI scale (p 0.806). No significant differences were found in terms of treatment duration either. Six patients (12%) had elevated aspartate aminotransferase (AST) and 9 (18%) had elevated alanine aminotransferase (ALT). No significant difference was found in FS values in relation to ALT, but it was with elevated AST (p 0.021). Similarly, differences were found in APRI based on AST (p 0.045). Metabolic syndrome was collected in 4 patients (8%) without significant differences with FS or APRI values. There were no significant differences in LF depending on gamma-glutamyl transpeptidase (GGT) values.Conclusion:FS and APRI score are useful for the determination of LF in RA patients treated with MTX. There is no evidence of a relationship between AD-MTX and LF by FS or APRI. AST values may be related to the presence of fibrosis as determined by FS or APRI. and the presence of the metabolic syndrome are not.References:[1]G.L. Erre, et al. Methotrexate therapy is not associated with increased liver stiffness and significant liver fibrosis in rheumatoid arthritis patients: A cross-sectional controlled study with real-time two-dimensional shear wave elastography. European Journal of Internal Medicine 69 (2019) 57–63. Internet.[2]R. Conway et al. Risk of liver injury among methotrexate users: a meta-analysis of randomised controlled trials. Semin Arthritis Rheum 2015 Oct;45(2):156–62. Internet.Disclosure of Interests:None declared