Liver Function Monitoring in Patients with Inflammatory Bowel Disease on Biologic Therapy

Baseline Testing and Monitoring

• All patients with inflammatory bowel disease (IBD) initiating biologic therapy, such as adalimumab (Humira), should have baseline liver function tests (LFTs) including complete blood count (CBC), liver profile (ALT, AST, bilirubin, alkaline phosphatase), and renal function tests, as recommended by the British Society of Gastroenterology 1, 2
• After initiating biologic therapy, LFTs should be monitored at weeks 2, 4, 8, and 12 after starting treatment, and then at least every 3 months thereafter during maintenance therapy, with more frequent monitoring in patients with pre-existing liver disease, concomitant hepatotoxic medications, or abnormal baseline LFTs 1, 2

Management of Liver Enzyme Elevations

• The risk of liver enzyme elevations is a known adverse event of biologic therapy, with ALT elevations ≥3× ULN occurring in 0.9% of adalimumab-treated patients with Crohn's disease in controlled trials, and severe hepatic reactions including acute liver failure have been reported in patients receiving TNF-blockers 1
• For moderate elevations (3-5× ULN), consider temporarily holding biologic therapy, investigate other potential causes of liver injury, and increase frequency of monitoring to every 3 days, while for severe elevations (> 5× ULN), discontinue biologic therapy temporarily, prompt hepatology consultation, and consider liver biopsy if etiology unclear 1, 3
• The following table summarizes the management of liver enzyme elevations:

Combination Therapy and Hepatotoxicity

• Patients on combination therapy with thiopurines or methotrexate may have increased risk of hepatotoxicity, requiring more vigilant monitoring, as recommended by the British Society of Gastroenterology and the European Association for the Study of the Liver 1, 4, 5
• Combination therapy with biologic therapy and other hepatotoxic medications requires close monitoring of liver function tests to detect potential hepatotoxicity early and prevent serious liver-related adverse events, with consideration of dose reduction or temporary discontinuation of non-essential medications if LFTs worsen 1, 4, 5

Screening and Prophylaxis for Hepatitis B

• All patients should be screened for hepatitis B before starting biologic therapy, as reactivation of hepatitis B can occur during anti-TNF therapy, and prophylaxis is mandatory in HBsAg positive patients, as recommended by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver 1, 6

Autoimmune Hepatitis and Other Considerations

• Rare cases of autoimmune hepatitis have been reported with anti-TNF therapy, characterized by elevated autoantibodies and specific histological findings, and may require discontinuation of therapy and corticosteroid treatment, as reported in the literature 1
• The American College of Rheumatology recommends including CBC with platelets to assess for bone marrow effects, while the National Institute for Health and Care Excellence advises that medications with minimal hepatic effects can be continued with monitoring 7, 5
• The American Association for the Study of Liver Diseases recommends discontinuing medications if LFTs >5x ULN despite medication adjustments, or if there is development of jaundice, encephalopathy, or coagulopathy, as stated in Alimentary Pharmacology and Therapeutics 8