Methotrexate is a form of chemotherapy used to treat various cancers and autoimmune diseases such as rheumatoid arthritis, psoriasis and Crohn's disease. Methotrexate is also valuable for managing ectopic pregnancies, whereby an embryo implants outside the uterus. According to a November 2010 review in "Cancer Management and Research," methotrexate interferes with cellular enzymes that recycle folic acid. Without folic acid, rapidly dividing cells, such as those found in tumors, cannot synthesize DNA and RNA, so they stop growing and reproducing. Like many drugs, methotrexate can be toxic to your liver.
Liver Enzymes
Your liver is a metabolically active organ. It is the primary site for detoxification of substances that are absorbed from your diet and is responsible for metabolizing medications and other potentially noxious agents that enter your body. To perform these important functions, your liver produces a wide array of enzymes, each of which performs a specific task. When your liver is damaged by toxins, infections or inflammation, its cells release their enzymes into your circulation, where they can be detected with blood tests.
Interpretation
Elevated liver enzymes are an indication of liver injury, but the degree of elevation is not necessarily an accurate indicator of the amount of damage being done to your liver. The chronicity of enzyme elevation may be a more accurate indicator of significant liver damage, as suggested in a January 2010 review in "Annals of the Rheumatic Diseases." This study showed that persistent increases in liver enzymes more often correlated with liver scarring than transient elevations. Thus, a single test showing elevated liver enzymes is difficult to interpret.
Risk Factors
Methotrexate has the potential to injure anyone's liver. However, certain risk factors increase your risk of methotrexate-induced liver damage, and you can take specific measures to minimize that risk. A study published in May 2003 in "Annals of the Rheumatic Diseases" demonstrated that individuals with a body mass index above 30 were more than twice as likely to experience liver damage from methotrexate when compared to patients with a BMI between 20 and 25. Your chances for developing liver toxicity from methotrexate are influenced by genetic factors, according to scientists at Washington University School of Medicine. Alcohol consumption or the use of other medications increases the likelihood of liver injury, while supplementing with folic acid helps reduce your risk.
Considerations
Methotrexate is a commonly prescribed agent for treating cancers, autoimmune illnesses and ectopic pregnancies. It interferes with the normal metabolism of folic acid in your cells, which inhibits cellular growth and division. Folic acid supplementation -- 1 mg daily is a standard dose during methotrexate therapy -- reduces your risk for liver toxicity, as does maintaining your ideal body weight. If your liver enzymes increase during methotrexate treatment, your doctor may ask you to repeat your blood test on a regular basis.
References
- "Cancer Management and Research"; Cancer Chemotherapy: Targeting Folic Acid Synthesis; N. Hagner, M. Joerger; November 2010
- "Annals of the Rheumatic Diseases"; Elevated Liver Enzyme Tests among Rheumatoid Arthritis and Psoriatic Arthritis Patients treated with Methotrexate and/or Leflunomide; J.R. Curtis, et al.; January 2010
- "Annals of the Rheumatic Diseases"; Factors Associated with Toxicity, Final Dose, and Efficacy of Methotrexate in Patients with Rheumatoid Arthritis; M. Hoekstra, et al.; May 2003
- "The Journal of Rheumatology"; Methotrexate (MTX) Pathway Gene Polymorphisms and Their Effects on MTX Toxicity in Caucasian and African American Patients with Rheumatoid Arthritis; P. Ranganathan, et al.; April 2008
