What is your approach to monitoring for hepatic fibrosis in chronic methotrexate use?

Historically, in lower-risk patients (e.g. rheumatoid arthritis patients who are less likely to have metabolic syndrome and are treated with lower doses), guidance has been to proceed with liver biopsy if repeated tests show elevated liver enzymes or hypoalbuminemia. In higher risk patients, (e.g. psoriasis patients who are more likely to have metabolic syndrome and treated with higher doses or patients who ingest alcohol or other hepatotoxic drugs), liver biopsy after cumulative 1.5 grams of MTX and repeat each 1 gram of cumulative dose has been recommended.

In practice, it is often difficult to obtain a liver biopsy (fewer hepatologists are trained than endoscopists; patients are reluctant to undergo an invasive test; accurate interpretation requires an experienced pathologist). Ultrasound-based transient elastography is a non-invasive alternative to detect fibrosis. I have no experience with this, but it may better detect established fibrosis compared to serologic makers like AST: platelet ratio (1).

Over the years, I have increasingly rotated therapies at the point a liver biopsy would be recommended for methotrexate monitoring in order to avoid the procedure. The availability of biologic drugs for many of the conditions historically treated with methotrexate has facilitated this change in practice. Notably, biologic drugs were associated with increased liver enzymes in methotrexate treated patients in a study excluding infliximab as a biologic agent (infliximab is the biologic most associated with autoimmune hepatitis) (2). So complete cessation of methotrexate rather than continued lower dosing with a biologic drug is prudent.

References:

• Olsson-White et al., PMID 33135387
• Schmajuk et al., PMID 24470205

Historically, dermatologists have routinely ordered liver biopsies in psoriatic patients receiving MTX. It was part of their guidelines. Rheumatologists have not for the most part. Psoriatic patients for whatever reason tend to develop more liver disease from MTX. Other factors that enhance MTX hepatotoxicity are: obesity, hyperlipidemia, diabetes, the metabolic syndrome, the use of other drugs such as statins, INH, rifampin, etc., for concomitant latent TB, underlying hepatitis C infection, etc. Here, I routinely across the board screen all patients with RA and arthritis in general for the presence of hep C infection. From a practical standpoint, if a patient begins to develop elevated LFTs on MTX, you monitor it and if these persist, you stop the MTX and refer the patient to GI hepatology for an investigation,