Determinants of serious liver disease among patients receiving low‐dose methotrexate for rheumatoid arthritis

Walker, Alexander M.; Funch, Donnie; Dreyer, Nancy A; Tolman, Keith G.; Kremer, Joel M.; Alarcón, Graciela S.; Lee, Randall G.; Weinblatt, Michael E.

doi:10.1002/art.1780360307

Cited by 175 publications

(98 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The ACR survey confirmed that liver enzyme values were likely to be abnormal in MTX-treated RA patients who developed clinically significant liver disease (10).…”

mentioning

confidence: 73%

See 1 more Smart Citation

Light and electron microscopic analysis of sequential liver biopsy samples from rheumatoid arthritis patients receiving long‐term methotrexate therapy followup over long treatment intervals and correlation with clinical and laboratory variables

Kremer

Kaye

et al. 1995

Arthritis & Rheumatism

Self Cite

View full text Add to dashboard Cite

Objective. To describe liver histopathologic features and ultrastructural changes in a prospectively studied cohort of rheumatoid arthritis (RA) patients receiving long-term methotrexate (MTX) therapy, and to seek correlations between these changes and simultaneously measured laboratory indices of liver function.Methods. This was a long-term, prospective, open observational study. Twenty-seven outpatients with RA who began therapy with MTX and continued treatment for extended periods underwent baseline and followup liver biopsies. One hundred seventy liver biopsy specimens were analyzed by light microscopy (LM) and assessed according to a modified Roenigk score and a newly devised numerical grading system. Ninety-three biopsy specimens were also analyzed by electron microscopy (EM). Blood samples were obtained at 4-6-week intervals for determination of bilirubin, alkaline phosphatase, aspartate aminotransferase (AST), and albumin levels, and the weekly dosage of MTX was adjusted if there were abnormalities in the AST or albumin level. A mean of 6.3 liver biopsies per patient were obtained over a mean followup period of 8.2 years (range 2-13 years).Results. cantly different from baseline at year 3, when it increased from a mean of 1.8 to 2.3 (P = 0.05) and at year 6, when it increased to 2.4 (P = 0.04), but this was not considered clinically meaningful. No other significant changes from baseline were observed by either LM grading system. No significant progression was observed by EM over the course of the investigation. Increases in serial measurements of AST correlated with both the modified Roenigk score (r = 0.21, P = 0.016) and the numerical rating score (r = 0.19, P = 0.027). Conclusion.Patients with RA who are receiving weekly single-dose oral MTX therapy exhibit little deterioration in hepatic architecture by LM or EM when the dosage of the drug is adjusted for abnormalities in AST and serum albumin, monitored at frequent intervals.

show abstract

“…The ACR survey confirmed that liver enzyme values were likely to be abnormal in MTX-treated RA patients who developed clinically significant liver disease (10).…”

mentioning

confidence: 73%

“…More recently, case reports have described significant liver disease in RA patients receiving MTX (6-9). A survey of the membership of the American College of Rheumatology (ACR) identified another 24 cases of cirrhosis and liver failure in patients with RA who had received therapy with the drug (10).…”

mentioning

confidence: 99%

Light and electron microscopic analysis of sequential liver biopsy samples from rheumatoid arthritis patients receiving long‐term methotrexate therapy followup over long treatment intervals and correlation with clinical and laboratory variables

Kremer

Kaye

et al. 1995

Arthritis & Rheumatism

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, as experience with the use of this drug in rheumatoid arthritis increased, it became apparent that liver toxicity was not common (8,9). While it is difficult to estimate risk, a 5-year cumulative incidence of cirrhosis was -1/1,000 treated patients in l retrospective study (9).…”

Section: Discussionmentioning

confidence: 98%

End‐stage liver disease developing with the use of methotrexate in heterozygous α₁‐antitrypsin deficiency

Hilsden¹,

Urbanski²,

Swain³

1995

Arthritis & Rheumatism

View full text Add to dashboard Cite

We report a case of cirrhosis developing in a man who was heterozygous for a,-antitrypsin deficiency and who was receiving methotrexate for severe rheumatoid arthritis. The a,-antitrypsin phenotype PiMZ has been associated with cryptogenic cirrhosis. Our patient had no biochemical or histologic evidence of chronic liver disease during the first year of receiving methotrexate. We postulate that the PiMZ state may result in enhanced susceptibility to methotrexate-induced hepatic toxicity and should be screened for if liver function abnormalities occur during methotrexate therapy.Methotrexate has proven to be an important addition to the rheumatologist's therapeutic armamentarium. With experience, concern about methotrexateinduced chronic liver disease has diminished. Routine liver biochemistry has been recommended as the surveillance method of choice, replacing liver biopsy (1); however, severe liver disease can develop in patients receiving methotrexate despite only minimal changes in serum liver biochemistry. Apart from those patients whose intake of alcohol is high, little is known about other patient subgroups in whom susceptibility to methotrexate hepatotoxicity might be enhanced.We describe here a man who was heterozygous for a,-antitrypsin deficiency, and who developed endstage liver disease while being treated with methotrexate for rheumatoid arthritis. CASE REPORTThe patient, a 75-year-old man, presented with hypoalbuminemia, pancytopenia, and coagulopathy.

show abstract

“…Many risk factors such as age, duration of exposure to MTX and its cumulative dose, history of Non Alcoholic Steatohepatitis (NASH), diabetes and obesity, hepatitis B or C virus infection, alcohol consumption and hepatotoxic drugs can increase the hepatotoxic effect of MTX (Lorenz and Knudtson, 2007;Diouf et al, 2001;Visser et al, 2009;Jones and Patel, 2000;Kremer et al, 1995;Langman et al, 2001;Leonard et al, 1987;Malatjalian et al, 1996;Reynold and Lee, 1986;Salliot, C. and Heijde D.V.D., 2009;Walker et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Hepatoprotective Effect of Taurine Against Oxidative Stress Due to Methotrexate in Rat

Issabeagloo¹,

Taghizadiyeh²,

Kermanizadeh³

2011

American Journal of Animal and Veterinary Sciences

View full text Add to dashboard Cite

Problem statement: Taurine, 2-aminoethanesulphonic acid is an essential amino acid. It is present at high concentrations in many tissues. It plays important roles in numerous physiological functions including conjugation with bile acids, modulation of calcium levels and maintenance of osmolarity, antioxidation and stabilization of membranes. Methotrexate (MTX), as the most disease modifying anti-rheumatic drug used for Rheumatoid Arthritis (RA), has been available for clinical use since 1951. The main scope of this study was to assessment of probable Hepatoprotective effect of taurine as it antioxidant action against oxidative stress due to methotrexate in rats. Approach: Eighty male Wistar rats, weighing 200±20 gr, were obtained from the animal breeding center of Islamic Azad University. The rats were divided into 4 equal groups of 20 animals including: 1-normal control, 2-normal rats treated with taurine, 3-taurine + methotrexate and 4-methotrexate. Results: Methotrexateinduced hepatotoxicity as reflected by elevated serum ALT, AST and GGT levels (p<0.001) and reduced serum total protein level (p<0.001). Conclusion: Taurine has a protective action against hepatotoxins and suggest that taurine may find clinical application against a variety of toxins where cellular damage is a consequence of reactive oxygen species.

show abstract

Determinants of serious liver disease among patients receiving low‐dose methotrexate for rheumatoid arthritis

Cited by 175 publications

References 12 publications

Light and electron microscopic analysis of sequential liver biopsy samples from rheumatoid arthritis patients receiving long‐term methotrexate therapy followup over long treatment intervals and correlation with clinical and laboratory variables

Light and electron microscopic analysis of sequential liver biopsy samples from rheumatoid arthritis patients receiving long‐term methotrexate therapy followup over long treatment intervals and correlation with clinical and laboratory variables

End‐stage liver disease developing with the use of methotrexate in heterozygous α₁‐antitrypsin deficiency

Hepatoprotective Effect of Taurine Against Oxidative Stress Due to Methotrexate in Rat

Contact Info

Product

Resources

About

Determinants of serious liver disease among patients receiving low‐dose methotrexate for rheumatoid arthritis

Cited by 175 publications

References 12 publications

Light and electron microscopic analysis of sequential liver biopsy samples from rheumatoid arthritis patients receiving long‐term methotrexate therapy followup over long treatment intervals and correlation with clinical and laboratory variables

Light and electron microscopic analysis of sequential liver biopsy samples from rheumatoid arthritis patients receiving long‐term methotrexate therapy followup over long treatment intervals and correlation with clinical and laboratory variables

End‐stage liver disease developing with the use of methotrexate in heterozygous α1‐antitrypsin deficiency

Hepatoprotective Effect of Taurine Against Oxidative Stress Due to Methotrexate in Rat

Contact Info

Product

Resources

About

End‐stage liver disease developing with the use of methotrexate in heterozygous α₁‐antitrypsin deficiency