Opinion Review
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Meta-Anal. Dec 28, 2021; 9(6): 488-495
Published online Dec 28, 2021. doi: 10.13105/wjma.v9.i6.488
Is dose modification or discontinuation of nilotinib necessary in nilotinib-induced hyperbilirubinemia?
You-Wen Tan
You-Wen Tan, Department of Hepatology, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang 212003, Jiangsu Province, China
Author contributions: Tan YW completed the paper independently.
Supported by the Social Development Project of Jiangsu Province, No. BE2020775; and Medical Project of Health Department Jiangsu Province, No. H2018021.
Conflict-of-interest statement: The author has no conflict of interest to disclose.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: You-Wen Tan, MD, Chief Doctor, Professor, Department of Hepatology, The Third Hospital of Zhenjiang Affiliated Jiangsu University, No. 300 Danjiamen, Runzhouqu, Zhenjiang 212003, Jiangsu Province, China. tyw915@sina.com
Received: December 29, 2020
Peer-review started: December 29, 2020
First decision: October 11, 2021
Revised: October 14, 2021
Accepted: December 24, 2021
Article in press: December 24, 2021
Published online: December 28, 2021
Processing time: 364 Days and 3.5 Hours
Abstract

Nilotinib is a specific breakpoint cluster region-Abelson leukemia virus-tyrosine kinase inhibitor that is used as an effective first- or second-line treatment in imatinib-resistant chronic myelogenous leukemia (CML) patients. Hepatotoxicity due to nilotinib is a commonly reported side effect; however, abnormal liver function test (LFT) results have been reported in asymptomatic cases. When alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are more than five-fold the upper limit of the normal (ULN) or when the serum total bilirubin level is more than three-fold the ULN, dose modification or discontinuation of nilotinib is recommended, resulting in decreased levels of hematological indicators in certain patients with CML. Nilotinib-induced hyperbilirubinemia typically manifests as indirect bilirubinemia without elevated ALT or AST levels. Such abnormal liver functioning is thus not attributed to the presence of a true histologic lesion of the liver. The underlying mechanism may be related to the inhibition of uridine diphosphate glucuronosyltransferase activity. Therefore, nilotinib dose adjustment is not recommended for this type of hyperbilirubinemia, and in the absence of elevated liver enzyme levels or presence of abnormal LFT findings, physicians should consider maintaining nilotinib dose intensity without modifications.

Keywords: Tyrosine kinase inhibitors; Nilotinib; Chronic myelogenous leukemia; Hyperbilirubinemia; Drug induced liver injure; Liver injury

Core Tip: Hepatotoxicity due to nilotinib is a commonly reported side effect; however, abnormal liver function test (LFT) results have been reported in asymptomatic cases. Nilotinib-induced hyperbilirubinemia manifests usually as indirect bilirubinemia without observation of elevated alanine aminotransferase or aspartate aminotransferase levels. The underlying mechanism may be related to the inhibition of uridine diphosphate glucuronosyltransferase activity. Therefore, in the absence of elevated levels of liver enzymes or presence of abnormal LFT findings, physicians should consider maintaining nilotinib dose intensity without modifications.