Rheumatoid Arthritis (RA) is an autoimmune disease known for causing inflammation and damage in the joints, but it is a systemic condition that affects the entire body. Because of this widespread action, various organs, including the liver, can be affected by the disease process. The liver plays a central role in filtering blood and processing chemicals, making it susceptible to issues arising from chronic inflammation and the medications used to treat the condition. Understanding the connection between RA and liver health is important for managing the disease.
How Systemic Inflammation Impacts Liver Health
The primary mechanism by which Rheumatoid Arthritis directly influences the liver is chronic systemic inflammation. The overactive immune system in RA releases inflammatory mediators, such as cytokines, into the bloodstream. These cytokines, including Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-6 (IL-6), travel throughout the body and can directly affect liver cells (hepatocytes).
The ongoing inflammation can manifest as a mild, persistent elevation of liver enzymes, sometimes called transaminitis, which is often asymptomatic. This enzyme increase signals stress or low-level damage to the liver tissue due to underlying disease activity. Chronic inflammation may also lead to the development of hepatic steatosis (fatty liver disease) and potentially nodular regenerative hyperplasia.
In rare cases, chronic RA inflammation can lead to more specific, severe complications. One condition is secondary amyloidosis (AA amyloidosis), where abnormal protein deposits build up in the liver and other organs, impairing function. Another rare, late-stage complication of severe RA is Felty’s Syndrome, which is associated with an enlarged spleen and may lead to liver enlargement and portal hypertension.
Medication-Induced Liver Injury in RA Treatment
The most frequent cause of abnormal liver tests in people with Rheumatoid Arthritis is the use of necessary medications. Disease-Modifying Antirheumatic Drugs (DMARDs) are the backbone of RA treatment, and some carry a risk of drug-induced liver injury. It is often challenging for doctors to determine if liver issues stem from underlying disease activity or treatment side effects.
Methotrexate (MTX), a widely prescribed DMARD, is the medication most commonly associated with liver toxicity, typically presenting as elevated liver enzyme levels. The risk of developing serious liver damage, such as fibrosis or cirrhosis, while taking MTX for RA is considered low. This is especially true when it is taken weekly as prescribed and with folic acid supplementation. However, the risk is related to the duration of therapy and the total cumulative dose received over time.
To manage this risk, doctors implement rigorous monitoring protocols using blood tests to check liver function every one to three months once a stable dose is achieved. Other DMARDs, such as leflunomide and sulfasalazine, also have the potential to cause liver enzyme elevations and require similar monitoring. Non-steroidal anti-inflammatory drugs (NSAIDs), often used for pain, can also contribute to liver strain. Diclofenac is one of the more commonly implicated NSAIDs in drug-induced liver injury, though this remains infrequent.
Newer treatments, like biologic DMARDs (bDMARDs), have a lower risk of causing severe liver injury compared to traditional DMARDs. Still, some may be associated with liver enzyme elevations, particularly in people with underlying liver conditions. RA management requires a balance where the benefits of controlling systemic inflammation outweigh the potential, monitored risks to the liver from necessary medications.
Recognizing Signs of Liver Dysfunction
Recognizing signs of liver dysfunction is important for individuals with Rheumatoid Arthritis, as liver changes are often silent until damage is advanced. Many people with liver involvement due to RA or its treatments may not experience noticeable symptoms initially. However, certain physical changes and symptoms warrant immediate communication with a healthcare professional.
Common symptoms of liver distress include fatigue, nausea, unexplained loss of appetite, and upper right abdominal pain. More obvious signs of advanced liver problems are jaundice (a yellowing of the skin and eyes), dark urine, or pale stools. Any sudden or persistent change in general well-being should prompt medical consultation.
Routine laboratory tests, specifically Liver Function Tests (LFTs), are the primary tool for early detection and monitoring of potential liver problems. These blood tests measure liver enzymes like Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST), which are released into the blood when liver cells are damaged. Regular LFTs allow the rheumatology team to detect asymptomatic enzyme elevations and adjust medication dosages before significant injury occurs. If LFTs are persistently abnormal, a doctor may recommend further evaluation, such as a liver ultrasound or, in rare cases, a liver biopsy, to assess the extent of damage.