[picapp align=”left” wrap=”false” link=”term=pills&iid=264092″ src=”0260/7b527e62-4510-44d3-9f43-b1afc1fd9d15.jpg?adImageId=10953550&imageId=264092″ width=”323″ height=”480″ /] Last month, for Rheumatology Journal Club, I chose an article about liver biopsy recommendations with methotrexate (MTX) use. The citation is: Lindsay et al. Liver fibrosis in patients with psoriasis and psoriatic arthritis on long-term, high cumulative dose methotrexate therapy. Rheumatology 2009 48(5):569-572.
The guidelines for MTX monitoring differ when comparing Dermatology with Rheumatology sources. According to a 1998 consensus conference of the American Academy of Dermatology, recommendations include a baseline liver biopsy at 2-4 months if there are risk factors for fibrosis and thereafter at a cumulative dose of 1-1.5g MTX. However, newer recommendations suggest liver biopsies may not be needed, especially in low-risk individuals. (Here is the abstract, but I’m not on the hospital network so I can’t get the full article). The 1994 ACR guidelines recommend monitoring liver enzymes, CBC, creatinine every 4-8 weeks, although more recent information (ACR meeting abstracts) suggests a 12 week interval may be appropriate. Certainly, monitoring interval is dependent on an individual’s risk factors. What are some risk factors that might cause us to pay closer attention to the liver? Diabetes, obesity (includes risk of NASH/NAFLD), impaired renal function, alcohol use and any history of prior abnormal liver biopsy.
So, back to the article. This study of 54 patients with psoriasis or psoriatic arthritis were on MTX (for an average of 6.5 years at a dose of about 15.5mg per week). Liver biopsies were done on all the patients and nearly 65% had normal biopsies. The rest had early mild fibrosis or fatty change. There were no cases of advanced fibrosis or liver disease. The authors did not note any significant correlation between risk factors and the likelihood of fibrosis. Alcohol use came closest but was not statistically significant. They also looked at a serum marker of liver fibrosis, pro-collagen 3 N-terminal peptide (PIIINP), which also did not correlate with liver fibrosis. This test is not approved in the US (that I could find, and according to my commercial office lab).
What does this mean for patients taking or contemplating MTX? Perhaps we can think of it as somewhat reassuring that the guidelines for monitoring became less strict with subsequent investigations. Clinical guidelines are backing away from liver biopsy, aside from circumstances where it is clinically indicated. Intervals between lab tests are lengthening. This is good news for patients, who are required to visit the lab less. However, the presence of risk factors, especially multiple risk factors in a patient, may warrant closer monitoring. This may be especially true with the prevalence of diabetes and obesity. Continued reminders against alcohol consumption when taking MTX are important, as is encouragement of weight loss. (Translation: If you take MTX, try to lose weight if you are overweight and do not drink alcohol and make sure you do your labs at the appropriate interval decided by you and your doctor)!