Methotrexate is the most commonly used disease-modifying anti-rheumatic drug (DMARD) used in the treatment of rheumatoid arthritis (RA). While it is extremely effective, it has potential side effects. Among them are reductions in blood cell counts (particularly white blood cells and platelets), mouth sores, skin rashes, fatigue, gastrointestinal upset, and liver toxicity.



When methotrexate was first introduced in the early 1980's, concern about the potential for liver toxicity prompted many rheumatologists to order liver biopsies before treatment and during treatment. Over the intervening years though, it has been apparent that the potential for liver toxicity is not as great as once thought.

However, liver toxicity is not something that should be ignored. This is particularly true since significant liver function abnormalities can occur without symptoms!

Careful monitoring of liver function through the use of blood tests is the best way to know if something serious is occurring with liver function.

Side effects such as cirrhosis are rare but can occur.

Liver function tests should be monitored at least monthly and more frequently when the dose is being adjusted upward.

At our center we used to extend monitoring out to six weeks but discovered that some patients got into trouble during that period so we went back to a 4 week schedule.

Liver function tests ensure that the liver is functioning properly. Aminotransferases (ALT and AST, also known as SGOT, SGPT) and albumin are the most important tests to watch.

If the tests are abnormal, then by holding the methotrexate, the blood tests should normalize. We usually repeat abnormal test 2-4 weeks after an initial abnormal reading. Many things other than methotrexate can cause the liver functions tests to rise. For example, sometimes viral infections can do this. Also, taking acetaminophen for pain can cause these abnormalities. Other drugs such as cholesterol lowering drugs can also cause this problem.

Supplementation with folic acid- usually 1-2 mgs a day can also reduce the incidence of liver function test abnormalities.

Liver biopsies are rarely performed nowadays, but in a patient who has chronically elevated liver function tests for which there is no ready explanation, a liver biopsy can provide important information.

It is extremely important that any patient who is started on methotrexate not only go through methotrexate teaching but also sign an informed consent form acknowledging they have received this teaching.