AB0178 CLINICAL ASPECTS OF HEPATIC STEATOSIS AND FIBROSIS IN NON-OBESE PATIENTS WITH RHEUMATOID ARTHRITIS AND PSORIATIC ARTHRITIS: EFFECTS OF CUMULATIVE DOSES OF METHOTREXATE
Authors: M. Ruiz-Ponce, L. Cuesta-López, M. D. López Montilla, M. L. Ladehesa-Pineda, A. Barranco, M. Á. Puche-Larrubia, C. Perez-Sanchez, M. D. C. Abalos-Aguilera, D. Ruiz-Vilchez, P. Ortiz-Buitrago, I. Ruiz-Cáceres, D. Corona-Mata, M. Casares-Jimenez, C. Lopez-Pedrera, A. Escudero-Contreras, E. Collantes-Estevez, C. López-Medina, I. Arias-de la Rosa, N. Barbarroja
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Liver damage is recognized as an extra-articular manifestation of psoriatic arthritis (PsA) and rheumatoid arthritis (RA), but the factors contributing to non-alcoholic fatty liver disease (NAFLD) in the context of inflammatory arthritis have not been fully elucidated. The potential hepatotoxic effects of methotrexate (MTX) remain as a controversial topic. <h3>Objectives:</h3> Liver damage is recognized as an extra-articular manifestation of psoriatic arthritis (PsA) and rheumatoid arthritis (RA), but the factors contributing to non-alcoholic fatty liver disease (NAFLD) in the context of Inflammatory Arthritis (IA) have not been fully elucidated. The potential hepatotoxic effects of methotrexate (MTX) remain as a controversial topic. <h3>Methods:</h3> A cross-sectional study was conducted in a cohort of 108 non-obese patients: 57 RA and 51 PsA. Clinical and laboratory parameters, liver disease biomarkers, and several indexes to evaluate the probability of suffering steatosis ("Hepatic Steatosis Index, HSI"; "Fatty Liver Index, FLI"; and "Triglycerides and Glucose Index, TyG") and/or hepatic fibrosis ("Fibrosis-4 score, FIB-4" and "Aspartate to Platelet Ratio Index, APRI") were analyzed. A transition hepatic elastography was performed using the FibroScan technique to assess the degree of hepatic stiffness or fibrosis, along with the CAP, to determine and quantify the percentage of fat infiltration in the liver. IA patients having methotrexate (57 in total: 33 RA + 25 PsA) were divided into two groups based on cumulative methotrexate doses (&lt;1.5g, non-hepatotoxic risk group, and &gt;1.5g, hepatotoxic risk group). The cumulative doses were retrospectively calculated from the beginning of the treatment until the day of blood collection, calculating the total milligrams administered per week during the treatment period. <h3>Results:</h3> Patients with RA had low disease activity (DAS28=2.85 ± 1.35) and a disease duration of 4.63 ± 4.84 years. On the other hand, PsA patients also exhibited low disease activity (DAPSA=11.38 ± 7.43) and a disease duration of 9.60 ± 6.63 years. Among all patients with IA (RA and PsA), analyses through FibroScan and CAP revealed that 51.9% had steatosis, while 7.50% show hepatic fibrosis, despite the absence of obesity. The risk indexes used in the study indicated that FLI was the most accurate index in identifying a higher percentage of patients with steatosis, according to the ROC curve analysis (AUC=0.733; p=0.0003). Among PsA patients, 47.10% had steatosis and 11.80% had hepatic fibrosis. PsA patients with steatosis showed significantly elevated levels of CRP. The 30% of PsA patients with steatosis had abnormal levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). On the other hand, 56.40% of RA patients had steatosis and 3.60% had hepatic fibrosis. RA patients with steatosis showed significantly elevated levels ACPAs and RF and triglycerides. In RA patients with steatosis had no abnormal levels of AST, ALT or ALP. Of note, no significant differences were found in the profiles of inflammatory, metabolic, and liver disease biomarkers, fibroscan and CAP values, as well as in the prevalence of steatosis and fibrosis between the two hepatotoxic risk groups due to MTX. <h3>Conclusion:</h3> 1) Patients with RA and PsA in the absence of obesity, exhibit a significant degree of hepatic steatosis, not reflected in abnormal biochemical, lipid and metabolic parameters, classical liver markers, or levels of hepatic enzymes, indicating a silent liver abnormality. 2) The hepatic damage indexes used failed to effectively identify IA patients with steatosis, highlighting the importance of exploring novel biomarkers. 3) All these findings emphasize the need for comprehensive hepatic evaluation and follow-up in IA patients with no obesity and low disease activity. 4) High cumulative doses of MTX do not appear to influence the presence of steatosis compared to low cumulative doses. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> Supported the "Instituto de Salud Carlos III" (PI20/00079 and RICOR-RD21/0002/0033) co-financed by the European Union. <h3>Disclosure of Interests:</h3> <b>None declared.</b>