Navigating the complex terrain of hepatitis B virus reactivation in the era of Bruton tyrosine kinase inhibitors

Abstract

In this editorial, we offer a summary of the risk associated with hepatitis B reactivation (HBVr) in the setting of both solid and hematologic malignancies treated with Bruton tyrosine kinase (BTK) inhibitors, with insights derived from current studies. Furthermore, we emphasize the critical need for a framework regarding robust risk evaluation in patients undergoing such treatments. This framework is essential for identifying those at increased risk of HBVr, enabling healthcare providers to implement proactive measures to prevent reactivation and ensure the safe administration of BTK inhibitor therapy.

Key Words: Hepatitis B virus reactivation, Bruton tyrosine kinase inhibitors, Hematologic malignancies, Solid tumors, Prophylaxis guidelines

Core Tip: This is an invited editorial for the coming paper “Risk of hepatitis B virus reactivation in oncological patients treated with tyrosine kinase inhibitors: A case report and literature analysis”.

INTRODUCTION

In this issue of the World Journal of Gastroenterology, Colapietro et al[1] emphasizes the assessment process for hepatitis B virus reactivation (HBVr) necessitates consideration of the patient’s underlying tumor type, distinguishing between solid tumors and hematologic malignancies, as this differentiation is critical in informing the decision-making process regarding HBVr prevention and management strategies.

In the rapidly evolving landscape of oncological and hematological therapy, the introduction of Bruton tyrosine kinase (BTK) inhibitors has heralded a new era of treatment potential, particularly for various lymphoid malignancies[2]. Among the myriad of challenges presented by these novel therapeutic agents, HBVr emerges as a significant concern lacking a comprehensive management and prophylaxis guidelines. Previous study conducted by Mak et al[3], illuminating the vacillating shadows of HBVr in patients administered BTK inhibitors, provides a crucial cornerstone for the meticulous delineation of this issue. The study’s emphasis on the lack of systematic prophylaxis against HBVr in patients receiving BTK inhibitors for hematologic malignancies is both timely and paramount. With HBVr rates climbing up to 8.3% in patients with previously resolved infections, the prudence of implementing prophylactic treatment with nucleos(t)ide analogues (NAs) cannot be overstated. The significance of this strategic approach is accentuated by the existing data, predominantly retrospective, which underlines the precarious position of patients poised on the cusp of potential viral reactivation. Furthermore, the synthesis of existing literature by Papatheodoridis et al[4], illustrating a discernible HBVr rate of 11% among hepatitis B virus surface antigen (HBsAg+) patients administered tyrosine kinase inhibitors (TKIs) without prophylaxis, unequivocally underscores the exigency for preemptive NA treatment in HBsAg+ individuals. This positions NA prophylaxis not as a mere precaution but as a clinical imperative for these patients, juxtaposed with a tailored strategy of close monitoring and on-demand NA therapy for HBsAg- patients. In some previous studies[5-12], the compelling narratives of HBVr in HBsAg- patients receiving BTK inhibitors, as documented in various case reports, embolden the call for a reclassification of these patients into an intermediate risk category for HBVr. Such reclassification is not only warranted but indispensable for crafting nuanced treatment modalities that encompass antiviral prophylaxis, thereby mitigating the risk associated with these powerful yet potentially hazardous therapies. The patient presented in the article by Colapietro et al[1], a 67-year-old Caucasian male with CLL, whose journey from treatment initiation to the abrupt confrontation with HBV reactivation, encapsulates the intricate interplay between innovative cancer therapy and the specter of viral resurgence. This case, emblematic of the broader dilemma, accentuates the pressing need for an agile and informed clinical approach that preemptively addresses the multifaceted challenge of HBVr. Based on these current literature reviews, patients who are HBsAg-negative and antiHBc-positive, receiving TKI therapy in the onco-hematological setting, should be reclassified as having an intermediate risk for HBV reactivation.

CONCLUSION

The studies highlighted herein, especially the one conducted by Mak et al[3], emphasize the urgent need for comprehensive guidelines. These should be carefully tailored to the nuanced risk profiles of patients treated with BTK inhibitors. In this significant issue of the World Journal of Gastroenterology, Colapietro et al[1] highlight the paramount importance of regularly updating guidelines. This process is critical to integrate the continuous influx of clinical evidence, thereby ensuring the healthcare community remains alert to the risk of HBVr during TKI therapy. They underscore that the dynamic nature of clinical research on BTK inhibitors and HBV reactivation necessitates a flexible approach to guideline development. Such an approach guarantees that preventive measures and management strategies reflect the latest knowledge, effectively reducing the risks associated with HBVr for patients undergoing TKI treatment. The proposed guidelines should incorporate a differential assessment that differentiates between types of malignancies, namely, solid tumors and hematologic malignancies. This differentiation is vital for enabling a stratified approach to both prophylaxis and management. Tailoring prevention and treatment strategies to the particular type of malignancy allows healthcare professionals to more efficiently mitigate the risk of HBVr and ensure optimal patient care in the context of BTK inhibitor therapy.