Systemic lupus erythematosus (SLE), commonly referred to as lupus, is a chronic autoimmune disease where the immune system mistakenly attacks the body’s healthy tissues and organs. This systemic inflammation can affect virtually any part of the body, including the skin, joints, kidneys, and brain. Lupus can cause liver damage, and liver abnormalities are detected in 25% to 60% of patients over the course of their disease. Although the liver is not a primary target organ in the diagnostic criteria for SLE, its involvement is frequent and stems from several distinct causes, making identification of the underlying problem necessary.
Autoimmune Attack: Lupus Hepatitis
Lupus can directly affect the liver through a specific inflammatory condition known as lupus hepatitis. This occurs when the immune system attacks the liver cells (hepatocytes), causing inflammation and damage. Lupus hepatitis is relatively uncommon, affecting an estimated 3% to 9% of all lupus patients.
The presentation often mimics classic autoimmune hepatitis (AIH). In some cases, the condition is associated with anti-ribosomal P antibodies, which are highly specific to SLE and may contribute to liver dysfunction. Histologically, the damage often appears as inflammation in the lobules or around the portal tracts of the liver.
When liver enzyme levels fluctuate in line with overall lupus disease activity, lupus hepatitis is the likely cause. However, the histology may sometimes be non-specific, making it challenging to distinguish from other types of liver injury. This direct autoimmune involvement is a diagnosis of exclusion, meaning other common causes of liver damage must be ruled out first.
Collateral Damage: Indirect Causes of Liver Injury
Liver issues in lupus patients are more frequently caused by indirect factors. A major contributor is Drug-Induced Liver Injury (DILI), which accounts for a substantial percentage of liver dysfunction. Many medications used to manage lupus, such as nonsteroidal anti-inflammatory drugs (NSAIDs), methotrexate, and azathioprine, are metabolized by the liver and carry a risk of hepatotoxicity.
The liver enzyme elevations caused by DILI are often mild and typically resolve after the suspected medication is discontinued. Glucocorticosteroids, a common treatment for SLE flares, can also lead to liver issues, including the development of fatty liver. In one study, DILI was identified as the cause of liver problems in about 31% of SLE patients presenting with liver dysfunction.
Secondary conditions associated with lupus also contribute to liver damage through non-autoimmune mechanisms. Patients with Antiphospholipid Syndrome (APS), which can overlap with SLE, are at risk for vascular issues like thrombosis in the hepatic veins. This can lead to serious conditions such as Budd-Chiari syndrome or portal vein thrombosis, impairing blood flow and causing liver damage.
Non-alcoholic fatty liver disease (NAFLD) is another common finding, accounting for a significant portion of liver abnormalities. The increased prevalence of NAFLD is often linked to metabolic issues, such as obesity and insulin resistance, which are more common in SLE patients, as well as the long-term use of corticosteroids.
Screening and Detection of Liver Issues
Routine monitoring for liver involvement is an important part of comprehensive lupus care, as many liver issues are asymptomatic in their early stages. The primary screening method involves regular blood work, specifically Liver Function Tests (LFTs), which measure enzymes like alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Elevated levels of these transaminases indicate that liver cells are being damaged or inflamed.
Patients should be aware of physical symptoms that may signal a liver problem, including persistent fatigue, abdominal pain, and jaundice (yellowing of the skin or eyes). If LFTs are persistently abnormal, non-invasive imaging, such as an abdominal ultrasound or CT scan, can help visualize the liver structure and detect issues like fatty changes or vascular blockages.
To distinguish between the multiple potential causes of liver injury, a liver biopsy is often necessary. A biopsy provides tissue samples that can show characteristic signs of lupus hepatitis, DILI, or coexisting autoimmune hepatitis (AIH). Accurately identifying the source of the damage is paramount for effective management, as treatment varies dramatically based on the cause.
Managing Liver Involvement in Lupus Patients
Treatment for liver involvement in lupus is highly dependent on the underlying cause identified. If the diagnosis confirms lupus hepatitis, management focuses on controlling systemic lupus activity with immunosuppressive therapy. This typically involves using corticosteroids, often in moderate to high doses, to quickly reduce the inflammation attacking the liver.
For cases of Drug-Induced Liver Injury (DILI), the intervention involves identifying the offending medication and either reducing its dosage or discontinuing it entirely. If non-alcoholic fatty liver disease (NAFLD) is the cause, the focus shifts to supportive care and lifestyle adjustments.
General management strategies include addressing metabolic risk factors through diet and exercise, which can help reverse fatty changes. Patients are also advised to minimize other potential hepatotoxins, such as excessive alcohol consumption or over-the-counter pain relievers, to reduce the overall burden on the liver.