Publications

@article{Atallah2023-ec,

title = {Risk of liver fibrosis associated with long-term methotrexate 

 therapy may be overestimated},

author = {Edmond Atallah and Jane I Grove and Colin Crooks and Esther Burden-Teh and Abhishek Abhishek and Sulleman Moreea and Kelsey M Jordan and Aftab Ala and David Hutchinson and Richard J Aspinall and Ruth Murphy and Guruprasad P Aithal},

year  = {2023},

date = {2023-05-01},

journal = {J. Hepatol.},

volume = {78},

number = {5},

pages = {989\textendash997},

publisher = {Elsevier BV},

abstract = {BACKGROUND \& AIMS: The risk of significant liver fibrosis from 

 prolonged methotrexate (MTX) exposure has been estimated at 

 around 5%, prompting intensive monitoring strategies. However, 

 the evidence is derived from retrospective studies that 

 under-reported risk factors for liver disease. We evaluated the 

 risk of long-term MTX therapy on liver fibrosis in a 

 longitudinal cohort study using two non-invasive markers. 

 METHOD: Between 2014-2021, adult patients diagnosed with 

 rheumatoid arthritis (RA) or psoriasis for $geq$2 years were 

 recruited prospectively from six UK sites. The MTX group 

 included patients who received MTX for $geq$6 months, whereas 

 the unexposed group included those who never received MTX. All 

 patients underwent full liver profiling, with transient 

 elastography (TE) and enhanced liver fibrosis (ELF) marker 

 measurements. RESULTS: A total of 999 patients (mean age 60.8 

 $±$ 12 years, 62.3% females) were included. Of 976 with valid 

 TE values, 149 (15.3%) had liver stiffness $geq$7.9 kPa. Of 

 892 with a valid ELF, 262 (29.4%) had ELF $geq$9.8. Age and 

 BMI were independently associated with elevated liver stiffness 

 and ELF. Neither MTX cumulative dose nor duration was associated 

 with elevated liver stiffness. Diabetes was the most significant 

 risk factor associated with liver stiffness $geq$7.9 kPa (adjusted odds ratio = 3.19; 95% CI 1.95-5.20; p \<0.001). 

 Regular use of non-steroidal anti-inflammatory drugs showed the strongest association with ELF $geq$9.8 (odds ratio = 1.76; 95% CI 1.20-2.56; p = 0.003), suggesting the degree of joint 

 inflammation in RA may confound ELF as a non-invasive marker of 

 liver fibrosis. CONCLUSION: The risk of liver fibrosis 

 attributed to MTX itself might have been previously 

 overestimated; there is a need to consider modifying current 

 monitoring guidelines for MTX. IMPACT AND IMPLICATIONS: Current 

 guidelines recommend intensive (2-3 monthly) monitoring 

 strategies for patients on long-term methotrexate therapy due to 

 the potential risk of liver fibrosis. Evaluation of the 

 association using two validated non-invasive markers of liver 

 fibrosis, liver stiffness and enhanced liver fibrosis score, in 

 a large cohort of patients with rheumatoid arthritis or 

 psoriasis shows that the reported risk has previously been 

 overestimated. The clinical focus should be to improve patients' 

 metabolic risk factors, diabetes and BMI, that are independently 

 associated with liver stiffness. There is a need to consider 

 modifying current treatment monitoring guidelines for 

 methotrexate.},

keywords = {Enhanced Liver Fibrosis, hepatotoxicity, liver   fibrosis, liver stiffness, Methotrexate, psoriasis, rheumatoid arthritis, transient elastography},

pubstate = {published},

tppubtype = {article}

}