From the Research
Untreated rheumatoid arthritis (RA) can lead to several liver complications over time, including hepatic steatosis, nodular regenerative hyperplasia, and portal hypertension, which can be prevented with early treatment using disease-modifying antirheumatic drugs (DMARDs) like methotrexate. The primary liver issues associated with untreated RA typically develop due to the chronic systemic inflammation that characterizes RA, as inflammatory cytokines like TNF-alpha and IL-6 can directly affect liver function 1. Additionally, patients with untreated RA may develop secondary amyloidosis, where abnormal protein deposits accumulate in the liver, impairing its function. Autoimmune hepatitis can also occur as a comorbidity with RA due to shared autoimmune mechanisms. Felty's syndrome, a complication of longstanding RA characterized by splenomegaly and neutropenia, may cause portal hypertension and subsequent liver damage.
Some key points to consider:
- The risk of liver toxicity is associated with the duration of methotrexate therapy and cumulative dose 2.
- Methotrexate hepatotoxicity is well documented, but the risk of serious liver disease in RA patients is small 1.
- The combination of methotrexate and leflunomide is generally safe and well tolerated, with no significant difference in liver enzyme elevations compared to methotrexate monotherapy 3.
- Regular liver function monitoring is essential for RA patients, with tests recommended every 3-6 months, even in well-controlled disease, to detect early signs of liver involvement.
Early treatment of RA with DMARDs like methotrexate (starting at 7.5-15mg weekly) can significantly reduce systemic inflammation and prevent liver complications. It is also important to note that the risk of liver toxicity associated with methotrexate use in RA patients is relatively low, and the benefits of treatment often outweigh the risks 4, 5. However, regular monitoring of liver function is still necessary to detect any potential abnormalities early on.
In terms of specific treatment recommendations, the following can be considered:
- Methotrexate: starting at 7.5-15mg weekly, with gradual dose escalation as needed and tolerated.
- Biologics: such as adalimumab (40mg every other week), or JAK inhibitors like tofacitinib (5mg twice daily) can be considered for patients who do not respond to methotrexate or have contraindications to its use.
- Regular liver function monitoring: every 3-6 months, even in well-controlled disease, to detect early signs of liver involvement.