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Methotrexate does NOT Cause Severe Liver Damage (when cumulative doses are monitored)

  • Take Home Message: 17% of patients on methotrexate develop mild fibrosis with a cumulative dose ranging from (1.4 to 3.3g). The drug appears to be safe as none of the patients developed worse liver damage (see comments and abstract) (Study from Malaysia)



-Recommendations for liver biopsies  are a cumulative dose of methotrexate of 1.5g

-In this retrospective study,  the liver damage at the first recommended biopsy was found to be the following (Grade1=46.4%, Grade 2=42.9%), Grade 3 (10.7%) = this means that 0% of higher Grades were reported !

-Roengik class IIIa refers to mild fibrosis (extending into the acini=space between liver cells (hepatocytes). IIIa can also infer present (or absent) fatty change, nuclear pleiomorphism and necroinflammation. Grade 3a requires more frequently performed liver biopsies (within 6 months instead of a 1.5-g cumulative dose of methotrexate). [grades 3b and 4 necessitate interruption and cessation of methotrexate treatment]

-The score was developed by dermatologists and is reliable. To view an article about the reliabilit og Roengik’s liver fibrosis classification system and its reliability: click HERE.

-It would be interesting in future studies to correlate the damage with Procollagen III levels.



-Background: Methotrexate with its known hepatotoxicity is used extensively in the management of moderate to severe psoriasis. Serum pro-collagen-III, fibroscan and liver biopsy are the modalities used to detect methotrexate induced liver fibrosis.

-Objective: To determine the rate of liver fibrosis in patients with psoriasis who received methotrexate.

-Methodology: Liver biopsy samples of patients who received methotrexate in Hospital Kuala Lumpur between 1999 and 2014 were identified and retrospectively studied. Histological changes were staged according to Roengik classification.

-Results: There were 28 patients with a total 35 liver biopsies. The mean age of patients at first liver biopsy was 46.4 years(range: 24-77) with mean duration of psoriasis of 11.7years(range:5-28) before biopsy. Seventeen(60.7%) patients had psoriatic arthropathy; 13(46.4%) had had prior exposure to other hepatotoxic medications; 8(28.6%) with diabetes mellitus; 5(17.8%) were overweight/obese; and 3(10.7%) had hyperlipidaemia. The median cumulative dose of methotrexate was 1506.5mg(range=1335-2772). Of all the first liver biopsies, 13(46.4%) were classified as Grade I; 12(42.9%) Grade II and 3(10.7%) Grade IIIa. Twenty-two patients continued to receive methotrexate after the first liver biopsy, of these only 5 underwent a second liver biopsy. The median cumulative dose of methotrexate was 2166mg(range=1927.5-3359.5); 4(80%) classified as Grade II and 1(20%) Grade IIIa. Subsequently 3 patients had the third liver biopsy at the median cumulative dose of 2680mg(Range:2545-3069.5); 1(33.3%) was Grade II and 2(66.7%) were Grade IIIa).

-Conclusion: About 17% of patients with psoriasis who received methotrexate developed mild fibrosis (Roengik class IIIa) with the cumulative dose between 1455-3360mg.


Reference: Regional Congress of Dermatology (RCD) 2016 – Singapore. RCD16-0175 Psoriasis HEPATIC CHANGES IN PATIENTS WITH PSORIASIS WHO RECEIVED METHOTREXATE: A REVIEW OF 35 LIVER BIOPSY SAMPLES IN HOSPITAL KUALA LUMPUR B.R. Lee1, M.M. Tang2, T. Suganthi2 1Universiti Putra Malaysia, Pathology, SERDANG- SELANGOR, Malaysia 2Hospital Kuala Lumpur, Dermatology, Kuala Lumpur, Malaysia