From the Guidelines
Elevated liver function tests (LFTs) are a common occurrence in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE or lupus), with approximately 6-50% of RA patients and 25-50% of lupus patients experiencing abnormal LFTs. These elevations are often mild to moderate and reflect the systemic inflammatory process rather than direct liver disease. In RA, elevated LFTs may result from the disease itself or from medications used to treat it, particularly methotrexate, leflunomide, and NSAIDs, as noted in a study published in the Annals of the Rheumatic Diseases 1. For lupus patients, liver abnormalities can stem from active lupus hepatitis, overlap with autoimmune hepatitis, fatty liver, drug-induced liver injury, or viral hepatitis. When elevated LFTs are detected during a flare, clinicians should evaluate for medication effects, consider viral hepatitis screening, and assess disease activity, as recommended by the 2021 American College of Rheumatology guideline for the treatment of juvenile idiopathic arthritis 1. Most cases resolve with appropriate management of the underlying rheumatic disease, though persistent or severe elevations warrant hepatology consultation. Regular monitoring of LFTs is recommended for patients with RA and lupus, especially those on hepatotoxic medications, with a monitoring schedule of every 1-2 months for the first few months and every 3-4 months thereafter, as suggested by a study published in Arthritis Care & Research 1. Key considerations for managing elevated LFTs in RA and lupus patients include:
- Evaluating medication effects and adjusting doses as needed, as recommended by a study published in the Annals of the Rheumatic Diseases 1
- Considering viral hepatitis screening and assessing disease activity, as noted in a study published in Arthritis Care & Research 1
- Monitoring LFTs regularly, especially in patients on hepatotoxic medications, as suggested by a study published in Arthritis Care & Research 1
- Referring patients with persistent or severe elevations to a hepatologist for further evaluation and management.
From the FDA Drug Label
Transient liver function test abnormalities are observed frequently after methotrexate administration and are usually not cause for modification of methotrexate therapy. Persistent liver function test abnormalities, and/or depression of serum albumin may be indicators of serious liver toxicity and require evaluation In clinical trials, leflunomide treatment as monotherapy or in combination with methotrexate was associated with elevations of liver enzymes, primarily ALT and AST, in a significant number of patients; these effects were generally reversible.
Elevated LFTs in RA or Lupus Flare: Elevated liver function tests (LFTs) can occur in patients with rheumatoid arthritis (RA) or lupus, particularly those taking medications such as methotrexate or leflunomide.
- Methotrexate: Transient LFT abnormalities are common, but persistent abnormalities may indicate serious liver toxicity.
- Leflunomide: Elevations of liver enzymes, primarily ALT and AST, can occur, but are generally reversible. It is essential to monitor LFTs regularly in patients with RA or lupus, especially those on medications that can affect liver function. If LFTs become elevated, the medication may need to be adjusted or discontinued to prevent serious liver toxicity 2 3.
From the Research
Elevated LFTs in RA and Lupus Flare
- Elevated liver enzymes are a common occurrence in patients with rheumatoid arthritis (RA) and can be caused by various factors, including the disease itself, anti-rheumatic medication, or associated autoimmune diseases 4.
- Studies have shown that the incidence of elevated liver enzymes in RA patients treated with methotrexate (MTX) is around 13-31% in the first three years of treatment 5.
- The use of MTX and leflunomide (LEF) in combination has been associated with a higher risk of elevated liver enzymes, with odds ratios ranging from 2.91 to 3.98 compared to monotherapy 6.
- Tumor necrosis factor inhibitors (TNF-Is) have also been linked to elevated liver enzymes, with infliximab (INF) showing the highest risk, followed by adalimumab (ADA) and etanercept (ETN) 7.
- Liver damage in RA patients can range from asymptomatic abnormal liver tests to cirrhosis, and it is essential to differentiate between hepatic manifestations of the primary disease and potential hepatotoxicity of medications 8.
- The clinical connection between RA and liver damage highlights the need for timely diagnosis and treatment of liver disease in RA patients to improve outcomes 8.