Rituximab Can Cause Elevated Liver Function Tests
Rituximab (Rytelo) can cause elevated liver function tests (LFTs) and monitoring of liver function is recommended during treatment. The FDA label for rituximab specifically mentions hepatotoxicity as a potential adverse effect, particularly in the context of hepatitis B virus (HBV) reactivation 1.
Mechanisms of Rituximab-Related Liver Enzyme Elevation
Rituximab can affect liver function through several mechanisms:
HBV Reactivation: The most serious liver-related adverse effect is HBV reactivation, which can lead to fulminant hepatitis, hepatic failure, and death 1.
Direct Drug Effect: Like many medications, rituximab may cause idiosyncratic drug reactions affecting the liver.
Immune-Mediated Effects: As an immunomodulator, rituximab can potentially trigger autoimmune phenomena affecting the liver.
Monitoring Recommendations
Based on clinical guidelines, the following monitoring approach is recommended:
Baseline Testing: Screen all patients for HBV infection by measuring HBsAg and anti-HBc before initiating rituximab 1.
During Treatment:
- Monitor liver function tests (ALT, AST, bilirubin) regularly
- For patients with evidence of current or prior HBV infection, monitor for clinical and laboratory signs of hepatitis or HBV reactivation during and for several months following rituximab therapy 1
Management of LFT Elevations
When LFT elevations occur during rituximab treatment, management should follow these guidelines:
ALT/AST >3× ULN: Consider interrupting therapy and expedite evaluation 2
ALT >3× ULN with bilirubin ≥2× ULN or ALT >5× ULN: Discontinue rituximab and refer to hepatology 2
HBV Reactivation: Immediately discontinue rituximab and any concomitant chemotherapy, and institute appropriate antiviral treatment 1
Special Considerations
Pre-existing Liver Disease
In patients with underlying liver disease, rituximab should be used with caution. However, interestingly, there is evidence that rituximab may actually improve liver function in certain autoimmune liver conditions:
- Case reports have shown successful treatment of refractory autoimmune hepatitis with rituximab, with normalization of liver enzymes after treatment 3, 4
Concomitant Medications
Be particularly cautious when using rituximab with other potentially hepatotoxic drugs. Monitoring should be more frequent in these cases.
Comparison with Other Biologics
TNF inhibitors also carry risks of LFT elevations, with infliximab showing the highest risk (OR 2.40 for LFTs >2× ULN), followed by adalimumab (OR 1.72), while etanercept showed the lowest risk (OR 1.10) 5. This suggests that the risk of hepatotoxicity varies among different biologic agents.
Conclusion
Rituximab can cause elevated liver function tests, primarily through HBV reactivation but also through direct or immune-mediated mechanisms. Regular monitoring of liver function is essential during rituximab treatment, with particular attention to patients with pre-existing liver disease or HBV infection. Management decisions should be based on the degree of LFT elevation and the presence of symptoms.