What to do if a patient on Remicade (infliximab) develops elevated liver function tests (LFTs)?

Management of Elevated Liver Function Tests with Infliximab (Remicade)

When a patient on Remicade (infliximab) develops elevated liver function tests (LFTs), the medication should be temporarily discontinued if ALT/AST levels exceed 5 times the upper limit of normal, and a thorough investigation of the abnormality should be undertaken.

Assessment of Elevated LFTs in Patients on Infliximab

Initial Evaluation

• Determine the pattern and severity of liver enzyme elevation:

  • Mild: 1-3× upper limit of normal (ULN)
  • Moderate: >3-5× ULN
  • Severe: >5× ULN 1

• Evaluate for other potential causes of liver injury:

  • Viral hepatitis (HBV, HCV)
  • Autoimmune hepatitis
  • Alcoholic liver disease
  • Non-alcoholic fatty liver disease
  • Concomitant hepatotoxic medications
  • Biliary obstruction 2, 1

Specific Testing

• Complete liver panel (ALT, AST, ALP, GGT, bilirubin)
• Viral hepatitis serologies (HBsAg, anti-HBc, anti-HCV)
• Autoimmune markers (ANA, IgG)
• Cross-sectional hepatobiliary imaging to exclude biliary obstruction 2
• Consider liver biopsy for grade ≥2 hepatitis (>3× ULN), steroid-refractory cases, or diagnostic uncertainty 2

Management Algorithm Based on Severity

Mild Elevation (1-3× ULN)

• Continue infliximab with close monitoring
• Monitor LFTs every 2-4 weeks
• Avoid other hepatotoxic medications
• Most mild elevations (85%) normalize spontaneously after a median of 17 weeks 3

Moderate Elevation (>3-5× ULN)

• Consider temporarily holding infliximab
• Monitor LFTs weekly until improving
• Investigate for other causes of liver injury
• If LFTs continue to rise despite holding infliximab, consider liver biopsy and hepatology consultation 2, 1

Severe Elevation (>5× ULN)

• Discontinue infliximab immediately
• Perform comprehensive workup including liver biopsy
• Consider corticosteroid therapy, especially if autoimmune features are present
• Consult hepatology 2, 1

Special Considerations

Drug-Induced Autoimmune Hepatitis

• Infliximab can cause drug-induced autoimmune hepatitis (DIAIH) 4
• Features include:
  • Positive autoimmune markers (ANA, elevated IgG)
  • Hepatocellular pattern of injury
  • Liver biopsy showing interface hepatitis with lymphoplasmacytic infiltration
• Treatment with corticosteroids is effective with prompt resolution of liver test abnormalities 4
• Median time from peak ALT to normalization is 45 days with corticosteroids vs. 77 days without 4

HBV Reactivation Risk

• Test all patients for HBV infection before initiating infliximab
• For HBsAg-positive patients, consult with a hepatologist
• Monitor HBV carriers closely throughout therapy and for several months after discontinuation
• If HBV reactivation occurs, stop infliximab and initiate antiviral therapy 1

Long-term Management

Patients Who Normalize LFTs

• If LFTs normalize and no clear alternative etiology is found:
  • Consider cautious rechallenge with infliximab with close monitoring
  • 82% of patients with idiopathic LFT elevations who continued infliximab normalized their LFTs 3

Alternative Biologics

• If infliximab must be permanently discontinued, consider switching to another biologic
  • 75% of patients with infliximab-induced liver injury successfully transitioned to another biologic (mostly adalimumab) without recurrence of liver injury 4

Monitoring After Resolution

• Monitor LFTs every 3-4 months after resolution
• Avoid concomitant hepatotoxic medications when possible

Prognosis

• Most cases of infliximab-related LFT elevations are mild and transient
• Severe hepatotoxicity requiring liver transplantation is rare
• Approximately 6% of IBD patients initiating anti-TNF therapy develop new-onset ALT elevations, but half of these can be linked to alternative etiologies 3

Remember that while infliximab can cause liver injury, discontinuation of treatment is rarely required for modest elevations of LFTs, and most abnormalities resolve spontaneously even with continued therapy 5.