Toxicity of targeted anticancer treatments on the liver in myeloproliferative neoplasms

Table 1 Biochemical classification of drug-induced liver injury

	Hepatocellular DILI	Mixed DILI	Cholestatic DILI
AASLD criteria for diagnosis of DILI	Elevation of ALT ≥ 3 times ULN and ALT/ALP ratio ≥ 5 times	ALT ≥ 3 times ULN, ALP ≥ 2 times ULN and ALT/ALP ratio < 5 but >2 times ULN	ALP ≥ 2 times ULN and ALT/ALP ratio of ≤ 2 times ULN
R value criteria for different patterns of DILI	R = (ALT/ULN)/(ALP/ULN) > 5	R = (ALT/ULN)/(ALP/ULN) < 5 and > 2	R = (ALT/ULN)/(ALP/ULN) < 2

ALP: Akaline phosphatase; ALT: Alanine Aminotransferase; DILI: Drug-induced liver injury; ULN: Upper limit of normal.

Table 2 Novel score for the decision of restarting or withdrawing imatinib in chronic myeloid leukemia[78]

Factors	Imatinib restart1	Imatinib withdrawal
Grade of hepatotoxic reaction
Grade 1	+	-
Grade 2	+2	-
Grade 3	+/-3	+/-
Grade 4 or presence liver transplantation or imatinib-induced liver cirrhosis or viral hepatitis reactivation	-	+
Presence of EMR to imatinib at 3 mo = BCR-ABL1IS ≤ 10%
Yes	+	-
No	-	+
Presence of EMR to imatinib at 6 mo = BCR-ABL1IS < 1% (if applicable4)
Yes	+	-
No	-	+
Use of another drug that might cause liver toxicity
Yes	+	-
No	-	+
Diagnosis of viral hepatitis established by PCR
Yes	+	-
No	-	+

¹Decide whether to restart imatinib only after resolution of acute hepatitis and normalization of liver function tests.

²Restart imatinib at a reduced or at the same dose.

³Restart imatinib if liver toxicity resolves in ≤ 1 month and there is no sign of recurrence.

⁴Do not take into consideration this factor if liver toxicity develops ≤ 6 months after imatinib initiation.

+: 1 point/yes; -: 0 points/no; ABL: Abelson Murine Leukemia; BCR: Breakpoint Cluster Region; EMR: Early molecular response; PCR: Polymerase chain reaction.