Hepatitis B Virus Reactivation in Gastrointestinal Stromal Tumor Patients Treated With Imatinib

Abstract

PurposeHepatitis B virus reactivation (HBVr) in patients with gastrointestinal stromal tumors (GISTs) have not been sufficiently characterized. This study aimed to review the possible mechanism of HBVr induced by imatinib and explore appropriate measures for patient management and monitoring.MethodsThe clinical data of GIST patients who experienced HBVr due to treatment with imatinib at Xiangya Hospital (Changsha, Hunan, China) were retrospectively analyzed. A literature review was also conducted.ResultsFive cases were analyzed, including 3 cases in this study. The average age of the patients was 61.8 y, with male preponderance (4 of 5 vs. 1 of 5). These patients received imatinib as adjuvant treatment (n=4) or as neoadjuvant treatment (n=1). Primary tumors were mostly located in the stomach (n=4) or rectum (n=1). High (n=3) or intermediate (n=1) recurrence risk was categorized using the postoperative pathological results (n=4). Imatinib was then started at 400 (n=4) or 200 mg (n=1) daily. Patients first reported abnormal liver function during the 2th (n=1),6th (n=3), or 10th (n=1) month of treatment with imatinib. Some patients (n=4) discontinued imatinib following HBVr; notably, 1 month after discontinuation, 1 patient experienced HBVr. Antivirals (entecavir n=4, tenofovir n=1), artificial extracorporeal liver support (n=1), and liver transplant (n=1) were effective approaches to treating HBVr. Most patients (n=3) showed favorable progress, 1 patient underwent treatment, and 1 patient died due to severe liver failure induced by HBVr.ConclusionsAlthough HBVr is a rare complication (6.12%), HBV screening should be conducted before starting treatment with imatinib in GIST patients. Prophylactic therapy for hepatitis B surface antigen positive patients, prompt antiviral treatment and cessation of imatinib are also necessary.

Sex‐specific incidence of hepatitis B virus flares among Bcr‐Abl tyrosine kinase inhibitor users in Taiwan

“…Poor adherence or underuse of TKI in CML patients during the first year after its introduction was associated with inferior prognosis especially among the very elderly population 22 . Among the TKI users, time to HBV reactivation that ranged from 1 week to 53 months have been reported, most likely during the first 6 months after TKI initiation 1–9 and our data showed a similar pattern. Incidence rates of hepatitis B flare of 2.33 and 3.33 per 100 person‐years in males and females were lower than that reported for HBV reactivation in a previously reported single‐institution study in Taiwan, which was 10.8 per 100 person‐years in patients with CML (5 HBV reactivation cases in 19 HBV carriers out of 142 CML patients) 23 .…”

“…In addition, imatinib is the first TKI that could effectively shrink the tumor size of gastrointestinal stromal tumor (GIST) before surgery. Hepatitis B virus (HBV) reactivation associated with Bcr‐Abl TKI use have been reported 1–9 . US Food and Drug Administration highlighted this concern and product labels were updated accordingly 10 .…”

Imatinib‐induced lichen planus and lichenoid drug eruption: A report of three cases

“…For the management of imatinib‐associated HBV reactivation, it is important that imatinib be stopped immediately. These patients should then be treated with appropriate antiviral therapy 3,4 …”

“…What makes this case even more interesting is the reactivation of hepatitis B, which is exceptional because only 13 cases of hepatitis B reactivation have been reported in the literature 3,4 . Among these 13 cases, seven patients received imatinib for CML, 5 patients for GIST, and one patient for a desmoid tumor 3,4 . The pathogenesis of imatinib‐related HBV reactivation is still unknown 3 .…”

“…However, imatinib‐induced lichen planus (LP) is an uncommon side effect with only four reported cases 2 . In addition, hepatitis B reactivation is an extremely rare association 3,4 . We report two cases of imatinib‐induced LP, one of which is associated with hepatitis B reactivation and one case of lichenoid eruption induced by imatinib.…”