Summary
The clinical utility of standard liver function tests for monitoring low dose pulse methotrexate therapy is reviewed in 163 rheumatoid arthritis patients over an eightyear period. Abnormalities of hepatic enzymes were seen in 58% of patients but led to cessation of therapy in only 5%. Moderate alcohol intake did not affect the frequency of liver test abnormalities. Abnormalities were seen more frequently in patients with longer duration of methotrexate therapy and in those with higher total dose. There was no correlation between liver test abnormalities and day of serum sampling relative to day of methotrexate dosing, nor was a correlation seen between liver test abnormalities and total weekly dose of methotrexate. Methotrexate has been demonstrated to be an effective drug in the treatment of rheumatoid arthritis. The clinical utility of standard liver tests to predict the potential for hepatotoxicity is questionable.
Similar content being viewed by others
References
Willkens, R.F., Watson, M.A., Paxson, C.S. Low dose pulse methotrexate therapy in rheumatoid arthritis. J Rheumatol, 1980, 7, 501–505.
Michaels, R.M., Nashel, D.J., Leonard, A., et al. Weekly intravenous methotrexate in the treatment of rheumatoid arthritis. Arthritis Rheum, 1982, 25, 339–341.
Weinstein, A., Marlowe, S., Korn, J., et al. Low-dose methotrexate treatment of rheumatoid arthritis. Long-term observations. Am J Med 1985, 79, 331–337.
Groff, G.D., Shenberger, K.N., Wilke, W.S., et al. Low dose oral methotrexate in rheumatoid arthritis: an uncontrolled trial and review of the literature. Semin Arthritis Rheum 1983, 12, 333–347.
Kremer, J.M., Lee, J.K.: The safety and efficacy of the use of methotrexate in long-term therapy for rheumatoid arthritis. Arthritis Rheum, 1986, 29, 822.
Williams, H.J., Willkens, R.F., Samuelson, C.O.Jr., et al. Comparison of low-dose oral pulse methotrexate and placebo in the treatment of rheumatoid arthritis. Arthritis Rheum 1985, 28, 721–730.
Weinblatt, M.E., Coblyn, J.S., Fox, D.A., et al. Efficacy of low-dose methotrexate in rheumatoid arthritis. New Engl J Med 1985, 312, 818–854.
Anderson, P.A., West, S.G., O'Dell, J.R., et al. Weekly pulse methotrexate in rheumatoid arthritis. Clinical and immunologic effects in a randomized, double-blind study. Ann Intern Med, 1985, 103, 489–496.
Farber, S. Temporary remissions in acute leukemia in chidren produced by folic acid antagonists, 4-aminopteroylglutamic acid (aminopterin). New Engl J Med, 1984, 56, 787–793.
Wetherley-Mein, G., Cottom, D.G. Portal fibrosis in acute leukemia. Br J Haematol, 1956, 2, 345–354.
Colsky, J., Greenspan, E.M., Warren, T.N. Hepatic fibrosis in children with acute leukemia treated with folic acid antagonists. Arch Pathol 1955, 56, 198–206.
Ryan, T.J., Vickers, H.R., Salem, S.N., et al. The treatment of psoriasis with folic acid antagonists. Br J Dermatol, 1964, 76, 555–564.
Reese, L.T., Grisham, J.W., Aach, R.D., et al. Effects of methotrexate on the liver in psoriasis. J Invest Dermatol, 1974, 62, 597–602.
Zachariae, H., Grunne, T.H.E., Sogaard, H. Liver biopsy in methotrexatetreated psoriatics — a re-evaluation. Acta Derm Venereol (Stockh), 1975, 55, 291–296.
Warin, A.P., Landells, J.W., Levene, G.M., et al. A prospective study of the effects of weekly oral methotrexate on liver biopsy. Br J Dermatol, 1975, 93, 321–327.
Ashton, R.E., Millward-Sadler, G.H., White, J.E. Complications in methotrexate treatment of psoriasis with particular reference to liver fibrosis. J Invest Dermatol, 1982, 79, 229–232.
Tolman, K.G., Clegg, D.O., Lee, R.G., Ward, J.R. Methotrexate and the liver. J Rheumatol, 1985, 12 (Suppl 12): 29–34.
Aponte, J., Petrelli, M. Hepatic histology following prolonged treatment of rheumatoid arthritis with bolus methotrexate. Abstract Arthritis Rheum, 1985, 28, S37.
Geronemus, R.G., Auerbach, R., Tobia, H. Liver biopsies vs liver scans in methotrexate-treated patients with psoriasis. Arch Dermatol, 1982, 118, 649–651.
Lawrence, C.M., Strange, R.C., Summerly, R., et al. Assessment of liver function using fasting bile salt concentrations in psoriasis prior to and during methotrexate therapy. Clin Chem Acta, 1983, 129, 341–351.
Lenler-Petersen, P., Sogard, H., Thestrup-Pedersen, K., et al. Glactose tolerance test and methotrexate-induced liver fibrosis and cirrhosis in patients with psoriasis. Acta Dermatovener (Stockholm) 1982, 62, 448–449.
Rodnan, G.P., Schumacher, H.R. Primer on the Rheumatic Diseases, 8th Ed., Atlanta, Arthritis Foundation, 1983, 207–208.
Zachariae, H., Kragballe, K., Thestrup-Pedersen, R. et al. HLA antigens in methotrexate-induced liver cirrhosis. Acta Dermatol Venereol (Stockh), 1980, 60, 165–166.
Zachariae, H., Kragballe, K., Sogaard, H. Methotrexate induced liver cirrhosis. Studies including serial liver biopsies during continued treatment. Br J Dermatol, 1980, 102, 407–412.
Weinstein, G., Roenigk, M., Mailbach, M., Cosmides, J., Halprin, K., Millard, M. Cooperative Study, psoriasis-liver methotrexate interactions. Arch Dermatol, 1973, 108, 36–42.
Nyfors, A. Liver biopsies from psoriatic related to methotrexate therapy. 3. Findings in post-methotrexate liver biopsies from 160 psoriatics. Acta Pathol Microbiol Scand, 1977, Sect A, 85, 511–518.
Dahl, M.G., Gregory, M.M., Schever, P.J. Liver damague due to methotrexate in patients with psoriasis. Br Med J, 1971, 1, 625–630.
Whaley, K., Webb, J. Liver and kidney disease in rheumatoid arthritis. Clin Rheum Dis, 1977, 3, 527–547.
Dahl, M.G., Gregory, M.M., Schew, P.J. Methotrexate hepatotoxicity in psoriasis. Comparison of different dose regimens. Br Med J, 1972, 1, 654–656.
Roenigk, H.H., Jr., Auerbach, R., Maibach, H.I., et al. Methotrexate guidelines — revised. J Amer Acad Dermatol, 1982, 6, 145–155.
Nyfors, A., Poulsen, H. Liver biopsies from psoriasis related to methotrexate therapy. Findings before and after methotrexate therapy in 88 patients. A blind study. Acta Path Microbiol Scand, 1976, 84, 262–270.
Horvath, E., Saibil, F.G., Kovacs, K., et al. Fine structural changes in the liver of methotrexatetreated psoriatics. Digestion, 1978, 17, 488–502.
Hoffmeister, R.T. Methotrexate therapy in rheumatoid arthritis: 15 years experience. Am J Med, 1983, 69–73.
Kremer, J.L. A long-term prospective study of methotrexate in rheumatoid arthritis. Abstract, Arthritis Rheum, 1985, 28, S68.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Leonard, P.A., Clegg, D.O., Carson, C.C. et al. Low dose pulse methotrexate in rheumatoid arthritis: an 8-year experience with hepatotoxicity. Clin Rheumatol 6, 575–582 (1987). https://doi.org/10.1007/BF02330596
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02330596