From the Guidelines
Infliximab can cause liver-related side effects, and patients should be monitored regularly for elevated liver enzymes and symptoms of liver damage, with treatment discontinuation considered if significant abnormalities occur 1.
Liver Side Effects of Infliximab
Infliximab, a TNF-alpha inhibitor, has been associated with various liver-related side effects, ranging from mild to severe. Common hepatic side effects include elevated liver enzymes (transaminases), which occur in approximately 5-8% of patients 1. More serious but rare complications include drug-induced liver injury, autoimmune hepatitis, cholestatic liver disease, and reactivation of hepatitis B in carriers.
Patient Risk Factors
Patients with pre-existing liver disease or hepatitis B infection are at higher risk for these complications 1. It is essential to screen patients for hepatitis B before starting treatment, and those with positive results may require antiviral prophylaxis during therapy.
Monitoring and Management
Regular liver function monitoring is recommended before starting infliximab and periodically during treatment, typically every 3-6 months 1. If a patient develops significantly elevated liver enzymes (greater than 3 times the upper limit of normal) or symptoms like jaundice, fatigue, abdominal pain, or dark urine, the medication may need to be discontinued.
Mechanism of Liver Effects
These liver effects occur because infliximab, as a TNF-alpha inhibitor, can alter immune responses in the liver and potentially trigger autoimmune reactions in susceptible individuals 1.
Key Recommendations
- Regular liver function monitoring is crucial for patients on infliximab therapy.
- Patients with pre-existing liver disease or hepatitis B infection require careful consideration and potential antiviral prophylaxis.
- Treatment discontinuation should be considered if significant liver abnormalities occur.
From the FDA Drug Label
Severe hepatic reactions, including acute liver failure, jaundice, hepatitis and cholestasis, have been reported in postmarketing data in patients receiving infliximab products. Autoimmune hepatitis has been diagnosed in some of these cases Patients with symptoms or signs of liver dysfunction should be evaluated for evidence of liver injury. If jaundice and/or marked liver enzyme elevations (e. g., ≥ 5 times the upper limit of normal) develop, RENFLEXIS should be discontinued, and a thorough investigation of the abnormality should be undertaken. Use of TNF blockers, including infliximab products, has been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers of this virus.
The side effects of infliximab related to the liver include:
- Severe hepatic reactions: acute liver failure, jaundice, hepatitis, and cholestasis
- Autoimmune hepatitis
- Hepatitis B virus reactivation in chronic carriers
- Elevations in hepatic aminotransferase levels Patients should be closely monitored for signs of liver injury, and infliximab should be discontinued if liver dysfunction occurs 2
From the Research
Side Effects of Infliximab on the Liver
- Infliximab, a tumour necrosis factor-α (anti-TNF-α) blocking agent, has been associated with hepatotoxicity, including mild to moderate elevations of liver enzymes and severe hepatitis 3.
- The main causes of liver dysfunction in patients treated with infliximab are reactivation of viral hepatitis and drug-induced liver injury 3.
- Infliximab-induced liver injury can manifest as drug-induced autoimmune hepatitis (DIAIH), which is commonly treated with corticosteroids 4.
- A study of 36 patients with infliximab-induced liver injury found that approximately half of patients were treated with corticosteroids, which led to a faster recovery 4.
- The use of infliximab has also been linked to autoimmune hepatitis, a rare but serious complication of treatment with anti-TNF-α agents 5.
- In some cases, infliximab-induced liver injury can occur after a single dose, suggesting a direct cytotoxic effect on the liver 6.
- However, infliximab has also been shown to have hepatoprotective effects in certain situations, such as in the case of paracetamol-induced hepatotoxicity in rats 7.
Clinical Characteristics of Infliximab-Induced Liver Injury
- The clinical characteristics of infliximab-induced liver injury include elevated liver enzymes, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 4.
- Patients with infliximab-induced liver injury may also have positive anti-nuclear antibody and/or elevated IgG levels 4.
- The time from onset of liver injury to peak ALT value can be longer in patients treated with corticosteroids 4.
- The use of corticosteroids can lead to a faster recovery and a lower risk of relapse in patients with infliximab-induced liver injury 4.