Sequential liver biopsies during long-term methotrexate treatment for psoriasis: a reappraisal

Abstract

One hundred and eighty-two liver biopsies were performed over a K)-year period on patients receiving long-term, low-dose, once weekly oral melhotrexate (MTX) lor severe psoriasis. Eorty-nine patients had two or more biopsies during continued treatment and formed the study population for our analysis. The first and last biopsies were compared to determine progression of any histological abnormalities. Liver bit)psies were assessed without knowledge ofthe MTX dose and allocated to one of five groups according to the severity ofthe histological abnormalities. These were detined as: (1) normal: (2) steatosis alone: (5) inflammation without fibrosis; (4) fibrosis: and (51 cirrhosis.The mean cumulative dose of MTX at the time of the first biopsy was 2743mg (range 315-10.024}. given over 275 weeks (range 26-738). In the interval between the first and last biopsies, patients received, on average, a further 23f)2mg (range 390-71 55) over 22S weeks (range 60-460}.There was improvement in the histological assessment in 12 patients, no change in 28 patients, and deterioration in nine patients. None developed cirrhosis. Liver biopsy findings prompted discontinuation of MTX in four ofthe 49 patients on long-term treatment. This has to be weighed against the cost and morbidity ofthe 124 biopsies performed in these patients. Our results suggest that, with careful follow-up, the risk of development or progression of liver disease in patients receiving long-term. low-dt)se. t)nce weekly oral MTX for psoriasis is modest, and that the requirement for performing routine liver biopsies in these patients needs to be reconsidered.

Have Methotrexate-Induced Liver Fibrosis and Cirrhosis Become Rare?

“…The test is not organ specifi c, and it is not a marker of fi brosis but of fi brogenesis. The study supported the view [4] that, as long as PIIINP is consistently normal in serial investigations, there is only a minimal risk of development of substantial liver fi brosis.…”

“…All guidelines have dealt specifi cally with the question of how to monitor hepatotoxicity and recommended the performance of liver biopsies, at least when the cumulative dose reached 1.5 g. Concern about the toxicity arose from a number of studies showing high frequencies of liver fi brosis (up to 50%) and cirrhosis (up to 26%) on long-term MTX treatment [2] . Within recent years, it has however been suggested that it is time to reconsider the use of liver biopsies in these patients [3][4][5][6] . Two main reasons for a reappraisal have been brought forward, the appearance of new noninvasive tests [3,4] and reports on the less frequent appearance of MTX-induced fi brosis and cirrhosis [5,6] .…”

“…Within recent years, it has however been suggested that it is time to reconsider the use of liver biopsies in these patients [3][4][5][6] . Two main reasons for a reappraisal have been brought forward, the appearance of new noninvasive tests [3,4] and reports on the less frequent appearance of MTX-induced fi brosis and cirrhosis [5,6] .…”

The Use of Transient Elastography and FibroTest for Monitoring Hepatotoxicity in Patients Receiving Methotrexate for Psoriasis

“…Liver fibrosis is the main disadvantage, although studies [1][2][3][4] vary on the prevalence of methotrexate-induced liver injury in patients with psoriasis. Frequent evaluation of liver enzyme levels and procollagen III peptide (PIIINP) levels 5,6 as well as periodic liver biopsies have been recommended during therapy.…”

“…These conditions increase the risk of liver disease and adverse effects related to the liver biopsy procedure. 4 In addition, the histologic accuracy of a liver biopsy may be affected by sampling error, pathologist inconsistency in observations, and discontinuous and semiquantitative histologic scoring systems.…”