Prevention of hepatitis B reactivation in patients with hematologic malignancies treated with novel systemic therapies:Who and Why?

The risk of reactivation in patients with chronic or past/resolved hepatitis B virus(HBV)infection receiving chemotherapy or immunosuppressive drugs is a wellknown possibility.The indication of antiviral prophylaxis with nucleo(t)side analogue is given according to the risk of HBV reactivation of the prescribed therapy.Though the advent of new drugs is occurring in all the field of medicine,in the setting of hematologic malignancies the last few years have been characterized by several drug classes and innovative cellular treatment.As novel therapies,there are few data about the rate of HBV reactivation and the decision of starting or not an antiviral prophylaxis could be challenging.Moreover,patients are often treated with a combination of different drugs,so evaluating the actual role of these new therapies in increasing the risk of HBV reactivation is difficult.First results are now available,but further studies are still needed.Patients with chronic HBV infection[hepatitis B surface antigen(HBsAg)positive]are reasonably all treated.Past/resolved HBV patients(HBsAg negative)are the actual area of uncertainty where it could be difficult choosing between prophylaxis and pre-emptive strategy.

Overview of the immunological mechanisms in hepatitis B virus reactivation:Implications for disease progression and management strategies

Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.

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

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.

Chronic hepatitis B and occult infection in chemotherapy patients-evaluation in oncology and hemato-oncology settings:The CHOICE study

BACKGROUND Reactivation of hepatitis B virus(HBV)infection is a well-known risk that can occur spontaneously or following immunosuppressive therapies,including cancer chemotherapy.HBV reactivation can cause significant morbidity and even mortality,which are preventable if at-risk individuals are identified through screening and started on antiviral prophylaxis.AIM To determine the prevalence of chronic HBV(CHB)and occult HBV infection(OBI)among oncology and hematology-oncology patients undergoing chemo-therapy.METHODS In this observational study,the prevalence of CHB and OBI was assessed among patients receiving chemotherapy.Serological markers of HBV infection[hepatitis B surface antigen(HBsAg)/anti-hepatitis B core antigen(HBc)]were evaluated for all patients.HBV DNA levels were assessed in those who tested negative for HBsAg but positive for total anti-HBc.RESULTS The prevalence of CHB in the study cohort was determined to be 2.3%[95%confidence interval(95%CI):1.0-4.2].Additionally,the prevalence of OBI among the study participants was found to be 0.8%(95%CI:0.2-2.3).CONCLUSION The findings of this study highlight the importance of screening for hepatitis B infection in oncology and hematology-oncology patients undergoing chemotherapy.Identifying individuals with CHB and OBI is crucial for implementing appropriate antiviral prophylaxis to prevent the reactivation of HBV infection,which can lead to increased morbidity and mortality.

Hepatitis B reactivation in cancer patients receiving immune checkpoint inhibitors:a systematic review and meta-analysis

Background Immunotherapy shows promise as a treatment option for various cancers.However,there is growing concern over potential complications from hepatitis B virus(HBV)reactivation after checkpoint blockade immunotherapy.Although most of the previous clinical trials on immune checkpoint inhibitors(ICIs)excluded patients with HBV,a few case reports and retrospective studies of HBV reactivation have been published.The aim of this study is to assess the risk of hepatitis B virus reactivation(HBVr)in patients receiving ICIs for advanced cancer.Methods English and Chinese language literature published prior to April 30,2023,was searched in PubMed,EMBASE,Web of Science,Cochrane,SinoMed,CNKI and Wanfang Data for studies reporting HBVr rates in cancer patients treated with ICIs.A pooled risk estimate was calculated for HBVr rates with 95%confdence intervals(CI).Results Data from 34 studies including 7126 patients were retrieved and analyzed.The pooled HBVr rate in cancer patients treated with ICIs was 1.3%(I^(2)=90.44%,95%CI:0.2-2.9%,P<0.001).Subgroup analysis revealed that patients diagnosed with hepatocellular carcinoma(HCC),HBV carriers,and patients from Asian regions or in developing countries have a higher rate of HBVr.Conclusions Our meta-analysis demonstrated a low risk of HBVr in patients treated with ICIs for advanced cancer.ICI treatment may be safely used in patients with existing HBV infection or chronic hepatitis B,accompanied by regular monitoring and appropriate antiviral prophylaxis if necessary.

Hepatitis B virus reactivation in rheumatoid arthritis

Rheumatoid arthritis(RA)is an autoimmune disease characterized by proliferative synovitis,which can cause cartilage and bone damage as well as functional limitations.Disease-modifying anti-rheumatic drugs have significantly improved the prognosis of RA patients.However,people with RA,when combined with hepatitis B virus(HBV)infection,may experience reactivation of HBV during treatment with anti-rheumatic drugs.The outcome of HBV reactivation(HBVr)varies from liver inflammation to liver failure,while insufficient HBV screening in RA patients has been reported in various countries.Therefore,it is necessary to identify patients at high risk before starting immunosuppressive therapy.The immune response plays an important role in anti-HBV infection.However,most anti-rheumatic drugs exert an inhibitory effect on the body’s immune system,resulting in HBVr.Therefore,it is necessary to conduct a comprehensive evaluation based on host factors,viral factors,and drug factors.In this paper,we summarize the mechanism of HBVr,the risk of HBVr caused by anti-rheumatic drugs,and the appropriate diagnosis and treatment process for RA patients so that clinicians can have a more comprehensive understanding of HBVr in RA patients.

Hepatitis B-related events in autologous hematopoietic stem cell transplantation recipients

AIM: To investigate the frequency of occult hepatitis B, the clinical course of hepatitis B virus (HBV) reactivation and reverse seroconversion and associated risk factors in autologous hematopoietic stem cell transplantation (HSCT) recipients. METHODS: This study was conducted in 90 patients undergoing autologous HSCT. Occult HBV infection was investigated by HBV-DNA analysis prior to transplantation, while HBV serology and liver function tests were screened prior to and serially after transplantation. HBV-related events including reverse seroconversion and reactivation were recorded in all patients. RESULTS: None of the patients had occult HBV prior to transplantation. Six (6.7%) patients were positivefor HBV surface antigen (HBsAg) prior to transplantation and received lamivudine prophylaxis; they did not develop HBV reactivation after transplantation. Clinical HBV infection emerged in three patients after transplantation who had negative HBV-DNA prior to HSCT. Two of these three patients had HBV reactivation while one patient developed acute hepatitis B. Three patients had anti-HBc as the sole hepatitis B-related antibody prior to transplantation, two of whom developed hepatitis B reactivation while none of the patients with antibody to HBV surface antigen (anti-HBs) did so. The 14 anti-HBs-and/or anti-HBc-positive patients among the 90 HSCT recipients experienced either persistent (8 patients) or transient (6 patients) disappearance of anti-HBs and/or anti-HBc. HBsAg seroconversion and clinical hepatitis did not develop in these patients. Female gender and multiple myeloma emerged as risk factors for loss of antibody in regression analysis (P < 0.05). CONCLUSION: Anti-HBc as the sole HBV marker seems to be a risk factor for reactivation after autologous HSCT. Lamivudine prophylaxis in HbsAg-positive patients continues to be effective.

Advances in treatment and prevention of hepatitis B

Chronic hepatitis B(CHB)continues to contribute to worldwide morbidity and mortality significantly.Scientists,clinicians,pharmaceutical companies,and health organizations have dedicated substantial Intellectual and monetary resources to finding a cure,increasing immunization rates,and reducing the global burden of CHB.National and international health-related organizations including the center for disease control,the national institute of health,the American Association for the study of liver disease(AASLD),The European association for the study of the Liver(EASL),The Asia Pacific association for the study of the Liver(APASL)and the world health organization release periodic recommendations for disease prevention and treatment.Our review of the most recent guidelines by EASL,AASLD,APASL,and Taiwan Association for the Study of the Liver revealed that an overwhelming majority of cited studies were published before 2018.We reviewed Hepatitis B-related literature published 2018 onwards to identify recent developments and current barriers that will likely direct future efforts towards eradicating hepatitis B.The breakthrough in our understanding of the hepatitis B virus life cycle and resulting drug development is encouraging with significant room for further progress.Data from high-risk populations,most vulnerable to the devastating effects of hepatitis B infection and reactivation remain sparse.Utilization of systems approach,optimization of experimental models,identification and validation of next-generation biomarkers,and precise modulation of the human immune response will be critical for future innovation.Within the foreseeable future,new treatments will likely complement conventional therapies rather than replace them.Most Importantly,pragmatic management of CHB related population health challenges must be prioritized to produce real-world results.

Hepatitis B and Hepatitis C Reactivation in the Biologic Era

Hepatitis B (HBV) and hepatitis C (HCV) reactivation may occur after the use of biologic agents. During the last decade, utilization of biologics has changed the fate of many treated for cancer, autoimmune and connective tissue disease, mainte-nance of transplanted organs, and the prevention of graft-versus-host disease among others. HBV reactivation has been reported in up to 50% of HBV carriers undergoing immuno-suppressive therapy, and there is emerging data pointing towards an increased risk for HCV reactivation. If reactivation of HBV and HCV occurs, the spectrum of clinical manifestations can range from asymptomatic hepatitis flares to hepatic decompensation, fulminant hepatic failure, and death. Therefore, identifying patients at risk and early diagnosis are imperative to decrease significant morbidity and mortality. The purpose of this article is to review the pathophysiology of the reactivation of HBV and HCV infection in patients receiving biologic therapies and the approaches used to diagnose, prevent, and treat HBV and HCV reactivation.

Hepatitis B virus reactivation in a chronic myeloid leukemia patient treated with imatinib mesylate

Imatinib mesylate is a molecular targeted agent for treating chronic myeloid leukemia （CML） and gastrointestinal stromal tumor. Although imatinib mesylate is not regarded as an immunosuppressive agent, few studies have also shown that it may impair immune response. In this report, we present a case of transient hepatitis B virus （HBV） reactivation during imatinib mesylate treatment for CML.