OA22 Methotrexate drug monitoring and referral patterns to Hepatology - can we improve detection and monitoring of hepatoxicity with methotrexate use?

Résumé fourni par la source

Abstract Background/Aims Methotrexate is a disease-modifying therapeutic, pivotal in the treatment of numerous rheumatological conditions. Hepatofibrosis secondary to methotrexate remains a concern for prescribers, with co-existence of metabolic risk factors contributing to hepatotoxicity. To date, no formal guidance exists on how to investigate or escalate concerns of liver toxicity in individuals prescribed methotrexate. Moreover, no highly sensitive, non-invasive, diagnostic test is available, with liver biopsy remaining the gold standard. The aim of this study was to review referral patterns to Hepatology and the utility of non-invasive testing modalities available. Results will subsequently inform a guideline that risk-stratifies hepatofibrosis development in patients taking methotrexate. Methods A retrospective study was conducted between January 2018 and September 2024. Patients aged ≥18, established on methotrexate therapy (≥1 month), referred from secondary care to Hepatology with concerns of hepatofibrosis were included. Patient data was collected from hospital electronic health records (Cerner), including information pertaining to individual demographics, methotrexate therapy, metabolic syndrome, LFTs, Fibroscan results, liver biopsy histology, referral rational and outcome. A Fibrosis-4 (FIB-4) index for liver fibrosis was calculated where possible, with high risk of advanced fibrosis defined as ≥ 1.3 in ≤ 65 years or ≥ 2 in aged ≥66. Results were analysed using descriptive statistics on Microsoft Excel. Results Of the 74 patients referred to Hepatology, 24 did not meet the study criteria. In the 50 patients included, 66% and 33% were referred from Rheumatology and Dermatology, respectively. Abnormal LFTs were cited in 68%, while 28% reported abnormal imaging. LFTs >2x upper normal of limit (ULN) were recorded in 22% of referrals, with 10% >3x ULN and 6% >5x ULN. Increased liver stiffness on Fibroscan (kPa ≥7.6) was detected in 28%, with 1 patient noted to have co-existing LFT derangement. Of 14 FIB-4 calculations, 1 was positive, with fibrosis subsequently confirmed histologically. All 7 liver biopsies performed confirmed hepatosteatosis/fibrosis histologically; only 5 of these had a Fibroscan kPa ≥7.6. Methotrexate was discontinued in 28% of referrals. Conclusion We show that most patients with Fibroscan findings indicating hepatofibrosis have LFTs within the normal range. Hence, LFT derangement should not be relied upon to identify patients at risk of hepatofibrosis while taking methotrexate. We also demonstrate that Fibroscans can incorrectly risk-stratify patients, with liver biopsy confirming fibrosis in individuals with negative Fibroscans. Similarly, we show FIB-4 calculations are not sensitive in detecting advanced fibrotic changes in this cohort, though interpretation is limited by patient numbers. As less than one third of Hepatology referrals lead to methotrexate cessation, and with Rheumatology as the primary referrer, collaborative working between these specialties is needed to devise referral guidance that risk stratifies patients correctly. For this, investment is essential to identify sensitive non-invasive screens tests that improve detection/monitoring of hepatofibrosis in this cohort. Disclosure K.E. Feather: None. C. Fleming: None. N. Sofat: None. A. Singanaygam: None.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.