Which laboratory test is particularly important to monitor during methotrexate therapy?

• A. Renal function tests
• B. Complete blood count
• C. Urinalysis
• D. Liver function tests

Answer: (D)

Methotrexate carries a real risk of liver injury, especially with long-term use. The liver is a primary organ for processing the drug, and toxicity can accumulate over time, potentially leading to hepatocellular damage or even fibrosis and cirrhosis. Because early liver injury often doesn’t cause symptoms, regularly checking liver function tests provides the best way to catch problems before they become serious. Measuring liver enzymes such as AST and ALT, along with bilirubin and alkaline phosphatase, helps detect hepatotoxicity early and guides decisions about continuing, adjusting, or stopping therapy. Baseline testing before starting methotrexate is essential, followed by periodic monitoring during treatment, with more frequent checks if risk factors are present (like alcohol use, obesity, or preexisting liver disease). While monitoring other organs is also important—renal function is relevant since methotrexate is cleared by the kidneys, and blood counts can reflect marrow suppression—the liver is the key concern to monitor specifically for methotrexate, making liver function tests the most critical test in this context.