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• W4328103580 abstract "Methotrexate-induced liver fibrosis: The end of a long-held beliefJournal of HepatologyVol. 78Issue 5PreviewThe chronic hepatotoxicity of methotrexate is a misconception that has been perpetuated for over 50 years.1 It is now time for it to be relegated to the history of inaccurate medical beliefs. Full-Text PDF Risk of liver fibrosis associated with long-term methotrexate therapy may be overestimatedJournal of HepatologyVol. 78Issue 5PreviewThe 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. Full-Text PDF Open Access In a stimulating editorial in this issue of Journal of Hepatology,[1]Di Martino V. Methotrexate-induced liver fibrosis: the end of a long-held belief.J Hepatol. 2023 Feb 26; (S0168-8278(23)00107-1. https://dx.doi.org/10.1016/j.jhep.2023.02.018. Online ahead of print. PMID: 36854346)Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar Vincent Di Martino contrasts our current study[2]Atallah E. Grove J.I. Crooks C. Burden-Teh E. Abhishek A. Moreea S. et al.Risk of liver fibrosis associated with long-term methotrexate therapy may be overestimated.J Hepatol. 2023 Jan 23; (S0168-8278(23)00020-X. https://dx.doi.org/10.1016/j.jhep.2022.12.034. Online ahead of print. PMID: 36702175)Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar with previous ones on methotrexate hepatotoxicity. It is worthwhile revisiting the key observations from our previous studies and rehearsing interpretations that were made in these articles. The first of our cohort studies questioning ‘are serial liver biopsies justified?’ involved 121 liver biopsies from 66 individuals and found ‘advanced hepatic fibrosis with low-dose methotrexate therapy to be much less frequent than previously reported’.[3]Aithal G.P. Haugk B. Das S. Card T. Burt A.D. Record C.O. Monitoring methotrexate induced hepatic fibrosis in patients with psoriasis: are serial biopsies justified?.Aliment Pharmacol Ther. 2004 Feb; 19 (PMID: 14871278): 391-399Crossref PubMed Scopus (122) Google Scholar None in this study developed cirrhosis or discontinued treatment on the basis of liver biopsy findings. The putative hypothesis that was put forward regarding the mechanism consistently stressed the interaction of the drug with the host and environmental factors.[4]Aithal G.P. Dangerous liaisons: drug, host and the environment.J Hepatol. 2007 Jun; 46 (PMID: 17445937): 995-998https://doi.org/10.1016/j.jhep.2007.03.017Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar,[5]Aithal G.P. Hepatotoxicity related to antirheumatic drugs.Nat Rev Rheumatol. 2011 Mar; 7 (PMID: 21263458): 139-150https://doi.org/10.1038/nrrheum.2010.214Crossref PubMed Scopus (132) Google Scholar Another study based on data from United States Organ Procurement and Transplantation Network involving 158,904 adults who had been listed for, and/or received liver transplantation concluded that the ‘burden of end-stage methotrexate-related liver disease to be exceedingly small, suggesting the need for reappraisal of current hepatotoxicity surveillance guidelines’.[6]Dawwas M.F. Aithal G.P. End-stage Methotrexate-related liver disease is rare and associated with features of metabolic syndrome.Aliment Pharmacol Ther. 2014 Oct; 40 (PMID: 25185870): 938-948Crossref PubMed Scopus (36) Google Scholar The discussion section in this article started with the quote ‘Methotrexate hepatotoxicity and the premature reporting of Mark Twain’s death: both greatly exaggerated’.[6]Dawwas M.F. Aithal G.P. End-stage Methotrexate-related liver disease is rare and associated with features of metabolic syndrome.Aliment Pharmacol Ther. 2014 Oct; 40 (PMID: 25185870): 938-948Crossref PubMed Scopus (36) Google Scholar In another article, we pointed out that the ‘evidence base published to date overwhelmingly supports the notion that features of the metabolic syndrome such as diabetes and obesity accentuate the risk of methotrexate related liver disease’.[7]Dawwas M.F. Aithal G.P. The quest for an evidence-based approach to surveillance for methotrexate-related hepatotoxicity: promise and perils.Br J Dermatol. 2015 Jun; 172 (PMID: 25523838): 1684-1685Crossref PubMed Scopus (3) Google Scholar It was Francis Scott Fitzgerald, one of the great American writers of the 20th century who wrote about ‘holding two opposing ideas in mind at the same time and still retain the ability to function’. The ‘null hypothesis’ proposes that no relationship and significance exists in a set of observed variables and measured phenomena. A scientist’s craft is to question, and loyalty rests with the observations; it is essential to recognise that truth is contextual rather than absolute. GPA is supported by NIHR Nottingham Biomedical Research Centre [BRC-1215-20003]. The views expressed are those of the authors and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health. The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details. The following are the supplementary data to this article: Download .pdf (.16 MB) Help with pdf files Multimedia component 1" @default.
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• W4328103580 title "Holding opposing ideas and the half-life of truth" @default.
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