Cancer Res Treat.  2020 Jan;52(1):181-188. 10.4143/crt.2019.131.

Factors Influencing Imatinib-Induced Hepatotoxicity

• Han JM
• Yee J
• Cho YS
• Gwak HS

• KMID: 2501212
• DOI: http://doi.org/10.4143/crt.2019.131

Abstract

Purpose
Although imatinib-induced hepatotoxicity may aggravate the patient’s clinical condition and alter the treatment plan, the underlying mechanism of and factors influencing imatinibinduced hepatotoxicity have rarely been investigated. The purpose of this study was to investigate factors affecting on the incidence of hepatotoxicity within 90 days after starting imatinib treatment and time to onset of imatinib-induced hepatotoxicity.
Materials and Methods
We retrospectively evaluated the records of 177 patients receiving imatinib from October 2012 to September 2017. The analyzed factors included sex, age, body weight, body surface area, underlying disease, and concomitant drugs.
Results
The proportion of patients with hepatotoxicity within 90 days after imatinib administration was 33.9%. Proton pump inhibitors (PPIs) increased the incidence of hepatotoxicity approximately 3.8-fold and doubled the hazard of time to reach hepatotoxicity. Patients with liver disease or hepatitis B virus (HBV) carriers had a more than 8-fold higher risk of hepatotoxicity and a 5.2-fold increased hazard of hepatotoxicity compared to those without liver disease or HBV. Patients with body weight under 55 kg had a 2.2-fold higher risk for occurrence of hepatotoxicity. Patients with an imatinib dose > 400 mg had a 2.3-fold increased hazard of time to reach hepatotoxicity compared to those with an imatinib dose ≤ 400 mg.
Conclusion
The findings of this study suggest that the use of PPIs and presence of liver disease or HBV were associated with imatinib-induced hepatotoxicity. Thus, close liver function monitoring is recommended, especially in patients with liver impairment or using PPIs.

Keyword

Imatinib mesylate; Chemical and drug induced liver injury; Time to reach hepatotoxicity; Proton pump inhibitors; Liver diseases; Hepatitis B virus

Figure

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  Fig. 1. Area under the receiver operating characteristic curve for factors affecting imatinib-induced hepatotoxicity. (A) Model I included for analysis the body surface area, presence of liver disease or hepatitis B virus infection, and proton pump inhibitors. (B) Model II included for analysis the body weight, presence of liver disease or hepatitis B virus infection, and proton pump inhibitors.

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