Table 3.

Severity scale, management and workup of IRH(^19,20,23)

	CTCAE Definition	Work-up	Management	Therapy
Grade 1	AST and ALT > 1–3 x ULN  ALP and GGT > 1–2.5 x ULN  Total bilirubine >1–1.5 x ULN	Weekly liver blood testsa	Continue ICI therapy	No treatment
Grade 2	AST and ALT > 3–5 x ULN  ALP and GGT > 2.5–5 x ULN  Total bilirubine >1.5–3 x ULN	Closer liver blood testsa as severity increases Limit/discontinue hepatotoxic medications Liver screening tests and imaging to rule out other causesb For Grade 3–4 consider hospitalization Only for Grade 4 consider liver biopsy	Drug-free period until liver blood tests recover to G1 levels	Consider corticosteroids if no improvement in 3–5 days and/or if adding symptoms
Grade 3	AST, ALT, ALP and GGT > 5–20 x ULN  Total bilirubin >3–10 x ULN		Permanently discontinue treatment	Corticosteroids; if no response in 3 days consider adding Mycophenolate Mofetil
Grade 4	AST, ALT, ALP and GGT > 20 x ULN  Total bilirubin >10 x ULN

CTCAE: common terminology criteria for adverse events; AST: aspartate aminotransferase; ALT: alanine aminotransferase; ALP: alkaline phosphatase; GGT: gamma-glutamyltransferase; ULN: upper limit of normal.

^aAST, ALT and bilirubin;

^bViral hepatitis, alcohol history, primary autoimmune hepatitis, iron studies, thromboembolic event, liver metastasis, primary malignancy.