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Immune-Related Adverse Events for GI Toxicity - Hepatitis

CTCAE-based severity grade for hepatitis from checkpoint inhibitor therapy using AST/ALT and bilirubin.

Immune-Related Adverse Events for GI Toxicity - Hepatitis
Higher of AST or ALT, as a multiple of the upper limit of normal (x ULN)
x ULN
Total bilirubin, as a multiple of the upper limit of normal (x ULN)
x ULN
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When to use

  • Grading hepatotoxicity attributed to immune checkpoint inhibitor therapy once other causes (viral, drug-induced, biliary obstruction, disease progression) have been excluded.

Formula

CTCAE v5.0 grading of AST/ALT and total bilirubin, each expressed as a multiple of the upper limit of normal (x ULN); overall grade is the higher of the two component grades. AST/ALT: Grade 1 >1-3x ULN, Grade 2 >3-5x, Grade 3 >5-20x, Grade 4 >20x. Bilirubin: Grade 1 >1-1.5x ULN, Grade 2 >1.5-3x, Grade 3 >3-10x, Grade 4 >10x.

Pearls and pitfalls

  • ICPi hepatitis is usually a hepatocellular (AST/ALT-predominant) pattern; a cholestatic pattern should prompt imaging to exclude biliary obstruction or sclerosing cholangitis.
  • Combination checkpoint inhibitor therapy (e.g., ipilimumab plus nivolumab) carries a substantially higher risk of severe hepatitis than monotherapy.

References

  1. Schneider BJ, Naidoo J, Santomasso BD, et al. J Clin Oncol. 2021;39(36):4073-4126.
  2. National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) v5.0.