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The document discusses the importance of antiviral prophylaxis to prevent herpes simplex virus (HSV) and varicella zoster virus (VZV) reactivation in adult patients with newly diagnosed acute leukemia. It highlights the efficacy of antiviral medications like acyclovir in reducing the incidence of symptomatic HSV reactivation during intensive chemotherapy. The study conducted in Italian centers belonging to SEIFEM group revealed a heterogeneous scenario in antiviral prophylaxis policies, with some centers not adhering to current international guidelines. The authors suggest the need for harmonization in applying antiviral prevention approaches and further prospective studies to optimize the schedule and duration of antiviral prophylaxis in different acute leukemia subgroups. [Extracted from the article]

Herpes simplex virus (HSV) infections in allogeneic haematopoietic stem cell transplantation (HSCT) recipients pose significant challenges, with higher incidence, severity, and risk of emergence of resistance to antivirals due to impaired T‐cell mediated immunity. This literature review focuses on acyclovir‐refractory/resistant HSV infections in HSCT recipients. The review addresses the efficacy of antiviral prophylaxis, the incidence of acyclovir‐refractory/resistant HSV infections, and the identification of risk factors and potential prognostic impact associated with those infections. Additionally, alternative therapeutic options are discussed. While acyclovir prophylaxis demonstrates a significant benefit in reducing HSV infections in HSCT recipients and, in some cases, overall mortality, concerns arise about the emergence of drug‐resistant HSV strains. Our systematic review reports a median incidence of acyclovir‐resistant HSV infections of 16.1%, with an increasing trend in recent years. Despite limitations in available studies, potential risk factors of emergence of HSV resistance to acyclovir include human leucocyte antigen (HLA) mismatches, myeloid neoplasms and acute leukaemias, and graft‐versus‐host disease (GVHD). Limited evidences suggest a potentially poorer prognosis for allogeneic HSCT recipients with acyclovir‐refractory/resistant HSV infection. Alternative therapeutic approaches, such as foscarnet, cidofovir, topical cidofovir, optimised acyclovir dosing, and helicase‐primase inhibitors offer promising options but require further investigations. Overall, larger studies are needed to refine preventive and therapeutic strategies for acyclovir‐refractory/resistant HSV infections in allogeneic HSCT recipients and to identify those at higher risk. [ABSTRACT FROM AUTHOR]

Background: The risk of hepatitis B virus (HBV) reactivation remains unclear in people with multiple sclerosis (MS) receiving ocrelizumab. We aimed to assess HBV seroprevalence and reactivation risk in MS patients on ocrelizumab and to evaluate the effectiveness of antiviral prophylaxis against HBV reactivation. Methods: In this single-center, cross-sectional study, 400 people with MS receiving ocrelizumab were screened for HBV at baseline and antiviral prophylaxis was implemented based on serological results. Patients were monitored for HBV reactivation, and outcomes were analyzed. Results: Among 56 (14%) patients who had serology compatible with occult or resolved HBV infection, 49 (85.7%) received antiviral prophylaxis regularly and had no HBV reactivation during the follow-up. Reactivation of HBV occurred in 2 out of 7 (28.6%) patients who did not receive antiviral prophylaxis and in one patient who did not adhere to the prophylaxis regimen. All patients with reactivation had anti-HBs levels below 100 mIU/mL and the median titer was significantly lower than the patients with no HBV reactivation (p = 0.034). Conclusion: This study highlights a 14% anti-HBc positivity, indicating a potential risk for HBV reactivation in people with MS receiving ocrelizumab. This suggests the importance of vigilant monitoring and the implementation of prophylactic measures. Our recommendation emphasizes antiviral prophylaxis, particularly for patients with low anti-HBs, and a pre-emptive strategy for others. [ABSTRACT FROM AUTHOR]

Yang Bo, Xiaojing Zhong, Yanping Xiang, Qingjun Ren, Pingsheng Hao Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of ChinaCorrespondence: Pingsheng Hao, Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, 39 Shi-Er-Qiao Road, Jinniu District, Chengdu, Sichuan, 610072, People’s Republic of China, Tel +86138 8196 5024, Fax +86-28-87732407, Email hpswl@126.comAbstract: We report a fatal case of disseminated herpes zoster in a patient with multiple myeloma, illustrating the severe risks immunocompromised individuals face from viral infections. By combining a detailed case report with an extensive literature review, the paper seeks to shed light on the underlying susceptibility factors for varicella-zoster virus infection in multiple myeloma patients. We further evaluate effective prophylactic protocols for herpes zoster, aiming to equip clinicians with improved therapeutic strategies. The case underscores the critical need for vigilant clinical assessments and tailored patient management to mitigate infection risks and enhance patient outcomes.Keywords: multiple myeloma, disseminated herpes zoster, antiviral prophylaxis, immunodeficiency

Objective: Cytomegalovirus (CMV) reactivation is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). Introduction of letermovir (LMV) seems to improve posttransplant outcomes, but delayed-onset CMV reactivation still remains a challenge. In this study, we report on our first experience with LMV prophylaxis in 93 CMV-seropositive adult patients receiving HSCT in our center. Materials and Methods: We retrospectively analyzed the data of 93 adult CMV-seropositive recipients receiving LMV as CMV prophylaxis after HSCT for hematological malignancies between 2019 and 2023. The starting LMV dose was 480 mg daily, reduced to 240 mg daily for those receiving cyclosporin A co-administration. CMV DNA in the blood was measured by real-time polymerase chain reaction weekly for the first 2 months after transplantation, then every other week until the end of immunosuppressive treatment. LMV was continued to day +100 or to CMV reactivation. Results: The median recipient age at the time of transplant was 51 (range: 20-71) years. All patients received grafts from peripheral blood, mostly for acute myeloid leukemia (60%). The median time from transplantation to LMV initiation was 3 (range: 0-24) days. While 55% of patients were transplanted from matched related donors, 32% had unrelated donors and 13% underwent haploidentical HSCT. Four patients (4%) had CMV “blips” while on LMV, but the drug was continued and repeated assays were negative. Only 2 patients (2%) experienced CMV reactivation while on LMV, on days 48 and 34 after HSCT, respectively. Seven patients (7%) developed late-onset CMV reactivation after a median of 124 days after HSCT (range: 118- 152 days) and they were successfully treated with ganciclovir. CMV disease was not observed. Grade III-IV acute graft-versus-host disease occurred in 6 patients (6%) during LMV treatment. LMV treatment was free of side effects. Conclusion: The median recipient age at the time of transplant was 51 (range: 20-71) years. All patients received grafts from peripheral blood, mostly for acute myeloid leukemia (60%). The median time from transplantation to LMV initiation was 3 (range: 0-24) days. While 55% of patients were transplanted from matched related donors, 32% had unrelated donors and 13% underwent haploidentical HSCT. Four patients (4%) had CMV “blips” while on LMV, but the drug was continued and repeated assays were negative. Only 2 patients (2%) experienced CMV reactivation while on LMV, on days 48 and 34 after HSCT, respectively. Seven patients (7%) developed late-onset CMV reactivation after a median of 124 days after HSCT (range: 118- 152 days) and they were successfully treated with ganciclovir. CMV disease was not observed. Grade III-IV acute graft-versus-host disease occurred in 6 patients (6%) during LMV treatment. LMV treatment was free of side effects.

Hepatitis B virus (HBV) reactivation is a condition marked by the return of HBV particles in patients whose HBV has previously cured or by an increase in HBV viremia in individuals whose HBV was previously chronic (CHB). Immunosuppressive treatments are more frequently the cause of reactivation; however, it can happen on its own. Reactivation can result in severe morbidity and death, but it can be avoided if screening identifies those who are at-risk and initiates antiviral prophylaxis, if necessary. Article highlights In patients with chronic hepatitis B infection and those who have previously been exposed to HBV, HBV reactivation (HBVr) has been found to be a side effect of immunosuppressive medications, namely cytotoxic chemotherapy. In people with previous exposure to HBV, the loss of HBV immunological control is the main early event in HBVr that results in a rise in HBV DNA. Patients with HBVr may experience a hepatitis flare-up if they have elevated levels of the enzymes aspartate aminotransferase (AST) or alanine aminotransferase (ALT). HBVr with hepatitis flare-ups can present as asymptomatic hepatitis to acute hepatitis with potentially lethal liver damage. Definition Elevation in HBV DNA compared with baseline or absolute increase if baseline is unavailable. Seroconversion to HBsAg positive for HBsAg-negative, HBcAb-positive patients. Pathophysiology Many infected patients during pregnancy go on to develop chronic hepatitis B (CHB) later in life because of persistent viral replication. Hepatocytes that have already experienced HBV infection are unfortunately susceptible to HBVr because HBV DNA might persist as covalently closed circular DNA (cccDNA) in these cells. Adult acute HBV infection usually goes away without causing CHB, chronic cccDNA still increases the chance of reactivation. Diagnosis Diagnostic criteria include the detection of HBsAg, elevations in ALT levels and elevations in baseline HBV DNA levels. Furthermore, HBVr has been defined as HBsAg reverse seroconversion with or without increased ALT levels. Stages of hepatitis B reactivation Stages of HB reactivation are as follows: Silent reactivation, which is characterized by an elevated viral load without overt hepatitis; HBV-associated hepatitis, which is characterized by an elevated viral load and evidence of histological, biochemical or clinical hepatitis. Fulminant liver failure, which is characterized by an elevated viral load along with hepatic synthetic dysfunction, encephalopathy and coagulopathy. Screening & risk stratification Any patient scheduled for cytotoxic chemotherapy or long-term immunosuppression should undergo screening for HBsAg and anti-HBc. Risk categorization based on virological status and IS regimen comes after HBV screening. Compared with patients with cured HBV, those with CHB are at a greater risk. The largest risk is associated with IS regimens in patients receiving hematopoietic stem cell transplant (HSCT) and B cell-depleting medications (e.g., rituximab). Risk factors Host factors- male sex, older age (50 y or above), presence of cirrhosis and hematologic malignancy. Virologic factors- high HBV DNA, HBsAg and HBeAg levels +ve, absence of anti-HBs, co-infection with HCV, HDV or HIV. IS regimen- its potency, dose and duration. Early studies shows that HBIg should be given in the perioperative period with aim to maintain high HBsAb titers (100–500 U/l) in the first few months following LT had beneficial effects. Management In patients listed for liver transplant: - start antivirals in patients with cirrhosis with detectable HBV-DNA. Post liver transplant patients: give HBIG+ Antivirals or Antivirals after evaluating risk factors. HBIG can be stopped once HBsAG-ve/ HBV DNA becomes undetectable. In non liver solid organ transplant patients, management depends on anti-HB core Ab and HBsAg status. Conclusion Reactivation of HBV is a dangerous illness that has a high risk of morbidity and death. If at-risk individuals are properly identified by screening and triaged to a suitable treatment regimen, reactivation can be prevented. According to current guidelines, patients who are most at risk, such as those with CHB undergoing cytotoxic regimens and B-cell-depleting medications, or recipients of stem cell transplants, should begin getting PPX prior to the initiation of immunosuppression and continue receiving it well after immunosuppression has ended. Future perspective Numerous screening approaches, such as risk-adaptive, risk-factor-based and universal screening, have been put forth. Tenofovir and entecavir generally have less evidence supporting their use in HBV prevention, but there is considerable evidence supporting their use in the treatment of CHB. There is a need for more well planned clinical studies to investigate these knowledge gaps. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus (CMV) infection is a common complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and in patients receiving novel hematological therapies. Its impact on morbidity and mortality necessitates effective management strategies. Despite recent advances in diagnostics and treatment, unresolved questions persist regarding monitoring and treatment, prompting the need for updated recommendations. Methods: A consensus was reached among a panel of experts selected for their expertise in CMV research and clinical practice. Key clinical areas and questions were identified based on previous surveys and literature reviews. Recommendations were formulated through consensus and graded using established guidelines. Results: Recommendations were provided for virological monitoring, including the timing and frequency of CMV DNAemia surveillance, especially during letermovir (LMV) prophylaxis. We evaluated the role of CMV DNA load quantification in diagnosing CMV disease, particularly pneumonia and gastrointestinal involvement, along with the utility of specific CMV immune monitoring in identifying at-risk patients. Strategies for tailoring LMV prophylaxis, managing breakthrough DNAemia, and implementing secondary prophylaxis in refractory cases were outlined. Additionally, criteria for initiating early antiviral treatment based on viral load dynamics were discussed. Conclusion: The consensus provides updated recommendations for managing CMV infection in hematological patients, focusing on unresolved issues in monitoring, prophylaxis, treatment, and resistance. These recommendations aim to guide clinical practice and improve outcomes in this high-risk population. Further research is warranted to validate these recommendations and address ongoing challenges in CMV management with emerging antiviral combinations, particularly in pediatric populations.

Objective: Cytomegalovirus (CMV) reactivation is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). Introduction of letermovir (LMV) seems to improve post-transplant outcomes, but delayed-onset CMV reactivation still remains a challenge. In this study, we report on our first experience with LMV prophylaxis in 93 CMV-seropositive adult patients receiving HSCT in our center. Materials and Methods: We retrospectively analyzed the data of 93 adult CMV-seropositive recipients receiving LMV as CMV prophylaxis after HSCT for hematological malignancies between 2019 and 2023. The starting LMV dose was 480 mg daily, reduced to 240 mg daily for those receiving cyclosporin A co-administration. CMV DNA in the blood was measured by real-time polymerase chain reaction weekly for the first 2 months after transplantation, then every other week until the end of immunosuppressive treatment. LMV was continued to day +100 or to CMV reactivation. Results: The median recipient age at the time of transplant was 51 (range: 20-71) years. All patients received grafts from peripheral blood, mostly for acute myeloid leukemia (60%). The median time from transplantation to LMV initiation was 3 (range: 0-24) days. While 55% of patients were transplanted from matched related donors, 32% had unrelated donors and 13% underwent haploidentical HSCT. Four patients (4%) had CMV "blips" while on LMV, but the drug was continued and repeated assays were negative. Only 2 patients (2%) experienced CMV reactivation while on LMV, on days 48 and 34 after HSCT, respectively. Seven patients (7%) developed late-onset CMV reactivation after a median of 124 days after HSCT (range: 118- 152 days) and they were successfully treated with ganciclovir. CMV disease was not observed. Grade III-IV acute graft-versus-host disease occurred in 6 patients (6%) during LMV treatment. LMV treatment was free of side effects. Conclusion: LMV prophylaxis was effective in preventing CMV reactivation with a favorable safety profile. CMV reactivation occurred mostly after LMV discontinuation; thus, extending the duration of prophylaxis beyond 100 days could be beneficial. [ABSTRACT FROM AUTHOR]

Background: The use of Bcr‐Abl TKI was found to be associated with hepatitis B (HBV) flares, with a more profound risk observed in females. This study was conducted to characterize the clinical features of patients with HBV flare among Bcr‐Abl TKI users, to estimate sex‐specific incidence rates of HBV flare, and to evaluate potential cumulative effect of Bcr‐Abl TKI. Methods: Bcr‐Abl TKI users with chronic HBV infection were identified from Taiwan's National Health Insurance database. The HBV flare cases were identified within the cohort. Incidence rates of HBV flare between men and women were assessed. Nested case–control analysis was used to evaluate the cumulative effect of Bcr‐Abl TKI use on HBV flare. Results: Among 415 patients with chronic HBV infection treated with Bcr‐Abl TKI from 2005 through 2018, 45 flare cases (28 males and 17 females) were identified. Days between Bcr‐Abl TKI initiation and HBV flare was 319 days in women compared to 610 days in men. 66.7% of the flares occurred during TKI therapy. Twelve of the 45 patients died, half of them died around 6 months after hepatitis B flare. Incidence rates of HBV flare were 2.34 and 3.33 per 100 person‐years in males and females, respectively. Higher incidence was observed among patients with chronic myeloid leukemia. Cumulative effect of Bcr‐Abl TKI on HBV flare was not observed. Conclusion: Approximately 10% of HBV carriers who used Bcr‐Abl TKI experienced HBV flare in Taiwan. The risk was higher in women and among patients with chronic myeloid leukemia. [ABSTRACT FROM AUTHOR]

Utilizing assays that assess specific T-cell-mediated immunity against cytomegalovirus (CMV) holds the potential to enhance personalized strategies aimed at preventing and treating CMV in organ transplantation. This includes improved risk stratification during transplantation compared to relying solely on CMV serostatus, as well as determining the optimal duration of antiviral prophylaxis, deciding on antiviral therapy when asymptomatic replication occurs, and estimating the risk of recurrence. In this review, we initially provide an overlook of the current concepts into the immune control of CMV after transplantation. We then summarize the existent literature on the clinical experience of the use of immune monitoring in organ transplantation, with a particular interest on the outcomes of interventional trials. Current evidence indicates that cell-mediated immune assays are helpful in identifying patients at low risk for replication for whom preventive measures against CMV can be safely withheld. As more data accumulates from these and other clinical scenarios, it is foreseeable that these assays will likely become part of the routine clinical practice in organ transplantation. [ABSTRACT FROM AUTHOR]

Utilizing assays that assess specific T-cell-mediated immunity against cytomegalovirus (CMV) holds the potential to enhance personalized strategies aimed at preventing and treating CMV in organ transplantation. This includes improved risk stratification during transplantation compared to relying solely on CMV serostatus, as well as determining the optimal duration of antiviral prophylaxis, deciding on antiviral therapy when asymptomatic replication occurs, and estimating the risk of recurrence. In this review, we initially provide an overlook of the current concepts into the immune control of CMV after transplantation. We then summarize the existent literature on the clinical experience of the use of immune monitoring in organ transplantation, with a particular interest on the outcomes of interventional trials. Current evidence indicates that cell-mediated immune assays are helpful in identifying patients at low risk for replication for whom preventive measures against CMV can be safely withheld. As more data accumulates from these and other clinical scenarios, it is foreseeable that these assays will likely become part of the routine clinical practice in organ transplantation.

The introduction of Hepatitis B Immunoglobulins (HBIg) prophylaxis at and after liver transplantation (LT) facilitated excellent long‐term survival of transplant patients with chronic hepatitis B virus (HBV) infection. Several studies suggested that only short‐term (i.e. 4–8 weeks) HBIg prophylaxis after LT followed by the long‐term administration of HBV polymerase inhibitors prevents HBV recurrence. In hepatitis D virus (HDV)/HBV co‐infected patients, the need for long‐term HBIg prophylaxis on top of HBV polymerase inhibitors is unknown. HDV requires HBV surface antigen (HBsAg) for uptake into hepatocytes to subsequently establish HDV replication. Data on HDV recurrence and its impact on outcomes after LT are limited. In this review, we evaluated the available data on post‐LT recurrence of HBV and/or HDV. Overall, HBIg prophylaxis was effective, but 10–13% of patients became HBsAg positive after LT. Only a single study from Turkey reported HDV recurrence, which was not observed in other LT centres. Since all studies administered continuous HBIg prophylaxis, the post‐LT recurrence rates without HBIg prophylaxis remain unknown. In a German study, the clinical course and histopathological aspects of liver injury (inflammation, fibrosis and steatosis) were similar in post‐LT patients on continuous HBIg and those who stopped HBIg after a median of 72 months. Discontinuation of HBIg in stable patients after LT for HBV/HDV co‐infection did not lead to impaired overall survival or a higher recurrence rate in this long‐term follow‐up. In summary, discontinuation of HBIg after liver transplantation for HBV/HDV liver disease seems safe, but randomized controlled studies are needed before it can be generally recommended. [ABSTRACT FROM AUTHOR]

Objectives: Induction therapy has been increasingly used in pediatric heart transplantation. This study evaluated the impact of anti‐thymocyte globulin (ATG) versus basiliximab as induction therapy on post‐transplant cytomegalovirus (CMV) infection, rejection at 1 year, coronary allograft vasculopathy (CAV), and mortality in pediatric heart transplant recipients receiving antiviral prophylaxis. Results: Of the 96 patients (age < 18 years) analyzed, 46 (47.9%) patients received basiliximab, and 50 (52.1%) received ATG. Median follow‐up was 3.0 (IQR, 1.7–4.9) years with 32.3% reporting CMV infection. The ATG group, as compared with the basiliximab group, had similar incidences of CMV infection (36% vs. 28.3%, p =.418), CMV viremia (22% vs. 19.6%, p =.769), and CMV‐positive tissue biopsy (30% vs. 22%, p =.486). The ATG group had lower incidences of rejection at 1 year (16% vs. 36.9%, p =.022) and CAV (4% vs. 23.9%, p =.006) with no difference in mortality (8% vs. 15.2%, p =.343), compared with the basiliximab group. Multivariate analysis showed that induction with ATG was associated with a lower risk of rejection at 1 year (OR,.31; 95% CI,.09–.94; p =.039) with no impact on the incidences of CMV infection (HR, 2.06; 95% CI,.54–7.89; p =.292), CAV (HR,.30; 95% CI,.04–2.58; p =.275), and mortality (HR,.39; 95% CI,.09–1.82; p =.233) compared to basiliximab induction. Discussion and conclusions: In conclusion, induction with ATG was associated with reduction in risk of rejection at 1 year with no effects on CMV infection, CAV, and mortality in pediatric heart transplant recipients with universal antiviral prophylaxis compared with basiliximab induction therapy. [ABSTRACT FROM AUTHOR]

HBV reactivation (HBVr) can be prevented by nucleos(t)ide analogues (NAs). We conducted a systematic review and meta-analysis on the risk of HBVr associated with new classes of immunosuppressive and immunomodulatory therapies and developed guidance on NA prophylaxis. An expert panel reviewed the data and categorised the risk of HBVr associated with each class of drugs into low (<1%), intermediate (1-10%), and high (>10%). Our search uncovered 59 studies, including 3,424 HBsAg+ and 5,799 HBsAg-/anti-HBc+ patients, which met our eligibility criteria. Based on medium-high quality evidence, immune checkpoint inhibitors, tyrosine kinase inhibitors, cytokine inhibitors, chimeric antigen receptor T-cell immunotherapies, and corticosteroids were associated with high HBVr risk in HBsAg+ patients; cytokine inhibitors, chimeric antigen receptor T-cell immunotherapies, and corticosteroids with intermediate risk in HBsAg-/anti-HBc+ patients; and anti-tumour necrosis factor agents and immune checkpoint inhibitors with low risk in HBsAg-/anti-HBc+ patients. Provisional recommendations are provided for drugs with low quality evidence. NA prophylaxis is recommended when using drugs associated with a high HBVr risk, while monitoring with on-demand NAs is recommended for low-risk drugs – either approach may be appropriate for intermediate-risk drugs. Consensus on definitions and methods of reporting HBVr, along with inclusion of HBsAg+, and HBsAg-/anti-HBc+ patients in clinical trials, will be key to gathering reliable data on the risk of HBVr associated with immunosuppressive or immunomodulatory therapies. [ABSTRACT FROM AUTHOR]

IntroductionOccult hepatitis B infection (OBI) is a condition where replication-competent hepatitis B virus-DNA (HBV-DNA) is present in the liver, with or without HBV-DNA in the blood [

Background: To conduct a meta-analysis with the aim of comparing the outcomes of antiviral prophylaxis and preemptive therapy for the prevention of cytomegalovirus (CMV) infection in liver transplant (LT) recipients. Methods: We searched databases for qualified studies up until March 2022. Finally, a meta-analysis was carried out using a fixed-effect or random-effect model based on the heterogeneity. Results: With a total of 1834 LT patients, the pooled incidence of CMV infection and CMV disease in the overall LT recipients using antiviral prophylaxis and preemptive therapy were 24.7% vs. 40.4% and 6.4% vs. 9.4%, respectively. Our meta-analysis exhibited a significant reduction in the incidence of CMV infection due to antiviral prophylaxis when compared to preemptive therapy in the high-risk group (OR: 6.67, 95% CI: 1.73, 25.66; p = 0.006). In contrast, there was a significant reduction in the incidence of late-onset of CMV disease in preemptive therapy compared to antiviral prophylaxis in the high-risk group (OR: 0.29, 95% CI: 0.12, 0.74; p = 0.009). However, the incidence of CMV disease, allograft rejection, graft loss, drug related adverse effects, opportunistic infections and mortality did not differ significantly between both the interventions (all p> 0.05). Conclusions: We found the use of antiviral prophylaxis, compared with preemptive therapy, is superior in controlling CMV infection and prolonging the time to CMV disease in LT recipients without an increased risk of opportunistic infections, allograft rejection, graft loss, drug related adverse effects, development of drug resistance, and mortality. [ABSTRACT FROM AUTHOR]

Introduction: Letermovir (LMV) is a new, cytomegalovirus (CMV)-specific, antiviral drug, approved in 2018 for CMV prophylaxis in patients after allogeneic hematopoietic transplantation. The introduction of letermovir prophylaxis has changed the management of CMV infection: it has reduced the incidence of CMV infections and CMV-related complications, and also improved the overall survival in CMV seropositive patients. However, until recently, due to its high treatment cost, prophylaxis with letermovir has not beeen a standard of care in Poland. Material and methods: To confirm the effectiveness and safety of letermovir prophylaxis, we collected real-life data from eight Polish transplant centers, in which a total of 53 patients were treated with letermovir, including off-label use. Results: LMV is characterized by low toxicity and good tolerability. There were no reports of special adverse events caused by LMV. Conclusions: Our experiences confirm the effectiveness and safety of letermovir prophylaxis, and suggest that this prophylaxis should be started as soon as possible after the infusion of stem cells, preferably no later than day 14. Moreover, our findings indicate that some patients could benefit from extended letermovir prophylaxis beyond 100 days after transplant. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) infection is one of the primary causes of morbidity and mortality following liver transplantation (LT). Based on current worldwide guidelines, the most effective strategies for avoiding post-transplant CMV infection are antiviral prophylaxis and pre-emptive treatment. CMV- IgG serology is the established technique for pretransplant screening of both donors and recipients. The clinical presentation of CMV infection and disease exhibits variability, prompting clinicians to consistently consider this possibility, particularly within the first year post-transplantation or subsequent to heightened immunosuppression. At annual symposia to discuss CMV prevention and how treatment outcomes can be improved, evidence on the incorporation of immune functional tests into clinical practice is presented, and the results of studies with new antiviral treatments are evaluated. Although there are ongoing studies on the use of letermovir and maribavir in solid organ transplantation, a consensus reflected in the guidelines has not been formed. Determining the most appropriate strategy at the individual level appears to be the key to enhancing outcomes. Although prevention strategies reduce the risk of CMV disease, the disease can still occur in up to 50% of high-risk patients. A balance between the risk of infection and disease development and the use of immunosuppressants must be considered when talking about the proper management of CMV in solid organ transplant recipients. The objective of this study was to establish a comprehensive framework for the management of CMV in patients who have had LT., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Cytomegalovirus (CMV) infection is a common complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and in patients receiving novel hematological therapies. Its impact on morbidity and mortality necessitates effective management strategies. Despite recent advances in diagnostics and treatment, unresolved questions persist regarding monitoring and treatment, prompting the need for updated recommendations., Methods: A consensus was reached among a panel of experts selected for their expertise in CMV research and clinical practice. Key clinical areas and questions were identified based on previous surveys and literature reviews. Recommendations were formulated through consensus and graded using established guidelines., Results: Recommendations were provided for virological monitoring, including the timing and frequency of CMV DNAemia surveillance, especially during letermovir (LMV) prophylaxis. We evaluated the role of CMV DNA load quantification in diagnosing CMV disease, particularly pneumonia and gastrointestinal involvement, along with the utility of specific CMV immune monitoring in identifying at-risk patients. Strategies for tailoring LMV prophylaxis, managing breakthrough DNAemia, and implementing secondary prophylaxis in refractory cases were outlined. Additionally, criteria for initiating early antiviral treatment based on viral load dynamics were discussed., Conclusion: The consensus provides updated recommendations for managing CMV infection in hematological patients, focusing on unresolved issues in monitoring, prophylaxis, treatment, and resistance. These recommendations aim to guide clinical practice and improve outcomes in this high-risk population. Further research is warranted to validate these recommendations and address ongoing challenges in CMV management with emerging antiviral combinations, particularly in pediatric populations., Competing Interests: Competing interests: The authors declare no conflict of Interest.

BackgroundTo conduct a meta-analysis with the aim of comparing the outcomes of antiviral prophylaxis and preemptive therapy for the prevention of cytomegalovirus (CMV) infection in liver transplant (LT) recipients.MethodsWe searched databases for qualified studies up until March 2022. Finally, a meta-analysis was carried out using a fixed-effect or random-effect model based on the heterogeneity.ResultsWith a total of 1834 LT patients, the pooled incidence of CMV infection and CMV disease in the overall LT recipients using antiviral prophylaxis and preemptive therapy were 24.7% vs. 40.4% and 6.4% vs. 9.4%, respectively. Our meta-analysis exhibited a significant reduction in the incidence of CMV infection due to antiviral prophylaxis when compared to preemptive therapy in the high-risk group (OR: 6.67, 95% CI: 1.73, 25.66; p = 0.006). In contrast, there was a significant reduction in the incidence of late-onset of CMV disease in preemptive therapy compared to antiviral prophylaxis in the high-risk group (OR: 0.29, 95% CI: 0.12, 0.74; p = 0.009). However, the incidence of CMV disease, allograft rejection, graft loss, drug related adverse effects, opportunistic infections and mortality did not differ significantly between both the interventions (all p> 0.05).ConclusionsWe found the use of antiviral prophylaxis, compared with preemptive therapy, is superior in controlling CMV infection and prolonging the time to CMV disease in LT recipients without an increased risk of opportunistic infections, allograft rejection, graft loss, drug related adverse effects, development of drug resistance, and mortality.

Organ transplantation is a life-saving treatment for patients with end-stage organ disease, a severe condition associated with a high risk of waitlist mortality. It is primarily limited by a shortage of available organs. Maximising available donors can increase access to transplantation. Transplantation from donors positive for HBV and HIV has increased in many countries. However, antiviral therapies need to be readily available for recipients after transplantation to prevent possible reactivation of the virus following the administration of immunosuppressive therapies. Furthermore, the intentional transmission of a virus has practical, ethical, and clinical implications. In this review, we summarise the current research, focusing on grafts from donors positive for the HBV surface antigen, antibodies against the HBV core antigen, and HIV, to help hepatologists and physicians interested in transplantation to select the best antiviral and/or prophylactic regimens for after transplantation. [ABSTRACT FROM AUTHOR]

Herpes zoster, which is due to the reactivation of Varicella zoster virus (VZV), is a leading cause of morbidity after allogeneic hematopoietic stem cell transplantation (allo-HSCT). While cell-mediated immunity (CMI) is critical to inhibiting VZV reactivation, CMI is not routinely assessed due to a lack of reliable tests. In this study, we aimed to evaluate VZVspecific CMI among allo-HSCT recipients (n = 60) and healthy individuals (HI, n = 17) through a panel of three immune functional assays after ex vivo stimulation by VZV antigen: quantification of (i) IFN-g release in the supernatants, (ii) T-cell proliferation after a 7-day stimulation of peripheral blood mononuclear cells (PBMC), and (iii) measurement of the ifn-g mRNA gene expression level after 24 h of stimulation of a whole-blood sample. VZV responsiveness was defined according to IFN-g release from VZV-stimulated PBMC. Upon VZV stimulation, we found that allo-HSCT recipients at a median time of 6 [5-8] months post-transplant had lower IFN-g release (median [IQR], 0.34 [0.12-8.56] vs. 409.5 [143.9-910.2] pg/ml, P <.0001) and fewer proliferating T cells (0.05 [0.01-0.57] % vs. 8.74 [3.12-15.05] %, P <.0001) than HI. A subset of allo-HSCT recipients (VZVresponders, n = 15/57, 26%) distinguished themselves from VZV-non-responders (n = 42/57, 74%; missing data, n = 3) by higher IFN-g release (80.45 [54.3-312.8] vs. 0.22 [0.12-0.42] pg/ml, P <.0001) and T-cell proliferation (2.22 [1.18-7.56] % vs. 0.002 [0.001-0.11] %, P <.0001), suggesting recovery of VZV-specific CMI. Interestingly, VZV responders had a significant fold increase in ifn-g gene expression, whereas ifn-g mRNA was not detected in whole blood of VZV-non-responders (P <.0001). This study is the first to suggest that measurement of ifn-g gene expression in 24-h-stimulated whole blood could be an accurate test of VZV-specific CMI. The routine use of this immune functional assay to guide antiviral prophylaxis at an individual level remains to be evaluated. [ABSTRACT FROM AUTHOR]

Herpes zoster, which is due to the reactivation of Varicella zoster virus (VZV), is a leading cause of morbidity after allogeneic hematopoietic stem cell transplantation (allo-HSCT). While cell-mediated immunity (CMI) is critical to inhibiting VZV reactivation, CMI is not routinely assessed due to a lack of reliable tests. In this study, we aimed to evaluate VZV-specific CMI among allo-HSCT recipients (n = 60) and healthy individuals (HI, n = 17) through a panel of three immune functional assays after ex vivo stimulation by VZV antigen: quantification of (i) IFN-γ release in the supernatants, (ii) T-cell proliferation after a 7-day stimulation of peripheral blood mononuclear cells (PBMC), and (iii) measurement of the ifn-γ mRNA gene expression level after 24 h of stimulation of a whole-blood sample. VZV responsiveness was defined according to IFN-γ release from VZV-stimulated PBMC. Upon VZV stimulation, we found that allo-HSCT recipients at a median time of 6 [5-8] months post-transplant had lower IFN-γ release (median [IQR], 0.34 [0.12–8.56] vs. 409.5 [143.9–910.2] pg/ml, P

The mother-to-child transmission of hepatitis B virus (HVB), frequent in endemic countries, accounts for about 40-50% of chronic HBV infections worldwide. Therefore, blocking the transmission is a significant step toward eliminating hepatitis B. The study presented a case of a successfully prophylactic baby girl born to a mother with chronic HBV infection diagnosed during pregnancy. She was prescribed antiviral therapy in the last trimester. The child was followed-up by the authors, proving her protection against HBV. In addition, we collected epidemiological data from family household contacts. The results revealed the source of the infection - the grandmother of the baby with chronic HBV infection. [ABSTRACT FROM AUTHOR]

Clinical reactivations of herpes simplex virus or varicella zoster virus occur frequently among patients with malignancies and manifest particularly as herpes simplex stomatitis in patients with acute leukaemia treated with intensive chemotherapy and as herpes zoster in patients with lymphoma or multiple myeloma. In recent years, knowledge on reactivation rates and clinical manifestations has increased for conventional chemotherapeutics as well as for many new antineoplastic agents. This guideline summarizes current evidence on herpesvirus reactivation in patients with solid tumours and hematological malignancies not undergoing allogeneic or autologous hematopoietic stem cell transplantation or other cellular therapy including diagnostic, prophylactic, and therapeutic aspects. Particularly, strategies of risk adapted pharmacological prophylaxis and vaccination are outlined for different patient groups. This guideline updates the guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) from 2015 "Antiviral prophylaxis in patients with solid tumours and haematological malignancies" focusing on herpes simplex virus and varicella zoster virus. [ABSTRACT FROM AUTHOR]

As a high-risk factor of perinatal HBV transmission, the potential role of maternal hepatitis B e antigen (HBeAg) to guide antiviral prophylaxis has not yet been fully reported. This large prospective cohort study enrolled 1177 hepatitis B surface antigen (HBsAg)-positive pregnant women without antiviral treatment and their newborns. HBeAg, HBsAg, and viral load in maternal serum collected before delivery were measured. All the newborns were given standard passive–active immunoprophylaxis within 12 h after birth, and post-vaccination serologic testing was performed at 7 (±7d) months of age. The results revealed that 20 of the 1177 infants (1.70%) were immunoprophylaxis failure, and all their mothers were HBeAg positive. Maternal quantitative HBeAg was positively correlated with viral load (r = 0.83; P 2 × 105 IU/mL, the sensitivity and specificity of maternal qualitative HBeAg to identify the risk of HBV MTCT for pregnant women and determine the necessity for antiviral prophylaxis was 95.5% and 92.6%, respectively. This study showed that maternal HBeAg can be a surrogate marker of HBV DNA for monitoring and evaluating whether antiviral prophylaxis is necessary for preventing perinatal HBV transmission.

Background: Hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)‐negative and hepatitis B core antibody (anti‐HBc)‐positive kidney transplant recipients ranges between 1.4% and 9.6%. Limited evidence is available regarding routine antiviral prophylaxis and identifiable risk factors for HBV reactivation in this population. Methods: In this multicenter retrospective study, we evaluated the prevalence of HBV reactivation in HBsAg‐negative anti‐HBc‐positive kidney transplant recipients who did or did not receive antiviral prophylaxis. The primary outcome assessed the prevalence of HBV reactivation, defined as a positive HBV DNA by PCR of any viral load at or above the minimal detection level. The principal safety outcomes assessed 1‐year graft survival, 1‐year all‐cause mortality, biopsy‐proven acute rejection, and antibody‐mediated rejection. Results: One hundred and sixty‐one patients met inclusion criteria and comprised two groups, antiviral prophylaxis (n = 14) and no antiviral prophylaxis (n = 147). Of patients who did not receive prophylaxis, only five (3.4%) experienced HBV reactivation, whereas one (7.1%) patient in the prophylaxis group experienced reactivation over a median follow‐up of 1103 days (p =.43). Furthermore, there were no differences with respect to all secondary outcomes. Statistical analysis demonstrated delayed graft function to be a significant factor associated with HBV reactivation. Conclusion: These study results suggest that the prevalence of HBV reactivation in HBsAg‐negative anti‐HBc‐positive kidney transplant recipients is low, regardless of antiviral prophylaxis. Furthermore, there were no significant graft‐related outcomes among those that did experience reactivation. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) can hide in the liver in the form of covalently closed circular DNA. When the body's immunity changes, HBV reactivation (HBV-R) can occur. The risk of HBV-R is determined by the complex interaction among virological factors, medication factors and host factors. However, many patients do not know that they are infected with HBV, and doctors often do not invest enough time to systematically evaluate the patient's HBV-R risk factors before immunosuppressive treatment. Therefore, HBV clinical screening should be vigorously promoted to achieve early detection and early prevention for patients with high risk of HBV-R. The mechanism, clinical features, risk factors, HBV-R under different disease etiologies, prevention and treatment of HBV-R were summarized to improve the in-depth understanding and awareness. [ABSTRACT FROM AUTHOR]

Background: Care home residents are at high risk from outbreaks of respiratory infections, such as influenza and COVID-19. We conducted a systematic review of randomized controlled trials, to determine which interventions (apart from vaccines) are effective at reducing transmission of acute respiratory illnesses (ARIs) in care homes., Methods: We searched CINAHL, Medline, Embase and Cochrane for randomized controlled trials (RCTs) of interventions to prevent transmission of ARIs in care homes (excluding vaccines), to April 2023., Results: A total of 21 articles met inclusion criteria. Two infection control interventions significantly reduced respiratory infections. Oseltamivir significantly reduced risk of symptomatic laboratory-confirmed influenza (OR 0.39, 95%CI 0.16-0.94, three trials), and influenza-like illness (OR 0.50, 95%CI 0.36-0.69), even in a vaccinated population. High dose vitamin D supplementation reduced incidence of ARIs (incidence rate ratio 0.60; 95%CI 0.38-0.94, one trial). Nine other RCTs of vitamin, mineral, probiotic and herbal supplements showed no significant effect., Conclusion: Transmission of respiratory infections in care homes can be reduced by educational interventions to improve infection control procedures and compliance by staff, by antiviral prophylaxis soon after a case of influenza has been detected, and by supplementation with high-dose Vitamin D3. Further research is needed to confirm the effect of high-dose Vitamin D3., (© The Author(s) 2024. Published by Oxford University Press on behalf of Faculty of Public Health.)

Background: Programmed cell death protein-1 (PD-1) inhibitor is recommended to treat advanced hepatocellular carcinoma (HCC). However, the safety of PD-1 inhibitor in patients with high HBV-DNA load is unknown because of the potential risk of hepatitis B virus (HBV) reactivation. This study was to compare the HBV reactivation between patients with low HBV-DNA loads and high HBV-DNA loads undergoing antiviral prophylaxis and PD-1 inhibitor. Methods: This was a retrospective study including consecutive hepatitis B surface antigen-positive HCC patients who received PD-1 inhibitor and concurrent antiviral prophylaxis for prevention of clinical hepatitis. Patients were divided into low HBV-DNA group (low group, ≤ 500 IU/ml) and high HBV-DNA group (high group, > 500 IU/ml) according to the baseline HBV-DNA level. The incidences of HBV reactivation, HBV-associated hepatitis, and PD-1 inhibitor disruption were compared between the two groups. Results: Two hundred two eligible patients were included: 94 in the low group and 108 in the high group. Seven patients (5 in the low group and 2 in the high group) developed HBV reactivation, and all recovered from HBV reactivation and HBV-associated hepatitis. The incidence of HBV reactivation in the two groups was low (5.3% vs 1.9%, P = 0.34). There was also no difference in the incidence of HBV-associated hepatitis (P = 0.56), or PD-1 inhibitor disruption (P = 0.82). The multivariable analysis showed PD-1 inhibitor with hepatic arterial infusion chemotherapy was the only significant risk factor for HBV reactivation (P = 0.04) and hepatitis (P = 0.002). Conclusion: With concurrent antiviral prophylaxis, HBV-DNA load higher than 500 IU/ml should not be a contraindication for PD-1 inhibitor. [ABSTRACT FROM AUTHOR]

Hepatitis B virus reactivation (HBV-R), which can lead to HBV-related morbidity and mortality, is a common and well-known complication that occurs during the treatment of non-Hodgkin lymphoma (NHL) patients with current or past exposure to HBV infection. HBV-R is thought to be closely associated with chemotherapeutic or immunosuppressive therapies. However, immunosuppressive agents such as anti-CD20 antibodies (e.g., rituximab and ofatumumab), glucocorticoids, and hematopoietic stem cell transplantation (HSCT) administered to NHL patients during treatment can cause deep immunodepression and place them at high risk of HBV-R. In this review, we explore the current evidence, the guidelines of several national and international organizations, and the recommendations of expert panels relating to the definition, risk factors, screening and monitoring strategies, whether to use prophylaxis or pre-emptive therapy, and the optimal antiviral agent and duration of antiviral therapy for HBV-R.

Hepatitis B virus reactivation (HBV-R), which can lead to HBV-related morbidity and mortality, is a common and well-known complication that occurs during the treatment of non-Hodgkin lymphoma (NHL) patients with current or past exposure to HBV infection. HBV-R is thought to be closely associated with chemotherapeutic or immunosuppressive therapies. However, immunosuppressive agents such as anti-CD20 antibodies (e.g., rituximab and ofatumumab), glucocorticoids, and hematopoietic stem cell transplantation (HSCT) administered to NHL patients during treatment can cause deep immunodepression and place them at high risk of HBV-R. In this review, we explore the current evidence, the guidelines of several national and international organizations, and the recommendations of expert panels relating to the definition, risk factors, screening and monitoring strategies, whether to use prophylaxis or pre-emptive therapy, and the optimal antiviral agent and duration of antiviral therapy for HBV-R. [ABSTRACT FROM AUTHOR]

Background: Since the onset of the new coronavirus pandemic, the world is facing a public health emergency. Repositioning hydroxychloroquine (HQ) seems to be a promising option. Many emerging evidences have converged on the effectiveness of HQ in the treatment of Covid-19 infection. In a recent paper, Gautret et al. suggested that further works are needed to determine if HQ antiviral prophylaxis is useful, especially for healthcare workers. Methods: The purpose of this paper is to assess the Covid-19 exposure and risks level among caregivers. For this, we performed research on internet and PubMed by crossing the following keywords: healthcare givers, healthcare workers, doctors, nurses, coronavirus, Covid-19, mortality, infection rate, chloroquine, hydroxychloroquine. Results: Data on healthcare worker's infection and mortality by Covid-19 are partial and are not systematically published. However, it seems that the infection rate varies between 3.8% and 9% depending on the country. Moreover, the mean age of this population is relatively old, especially in the OECD area. Conclusions: Anti-Covid-19 HQ prophylaxis should be urgently accessed, especially for healthcare workers. It is to be hoped that HQ prophylaxis reduces the morbidity and mortality from Covid-19 infection among this population which is particularly exposed and relatively old.

Cytomegalovirus (CMV) infection plays an important role in clinical transplantology – it increases the risk of complications, graft failure, and patient death. The virus has both direct (direct damage to organs and tissues) and indirect immunomodulatory effects. Based on studies conducted, an international group of experts developed general principles for managing CMV infection after transplantation. This paper discusses risk factors, pathogenetic mechanisms by which CMV infection develops after kidney transplantation, the principles of diagnosis, treatment and prevention of this complication, and ways to overcome drug resistance in the virus. The prospects for the use of immunological monitoring, new antiviral drugs, as well as the possibility of using CMV vaccines, T-cell therapy, immunosuppressants (antiviral mTOR inhibitors) are discussed.

Prophylactic antiviral treatment is controversial due to a lack of studies in both HBsAg negative/HBcIgG positive patients who treated conventional chemotherapy with solid malignancy, unlike HBsAg positive. In this cross-sectional and retrospective study, we analyzed that the reactivation risk of Hepatitis B Virus (HBVr) of totally 457 HBcIgG positive patients with solid cancer in archives records between 2011 and 2018 years of two different centers. Totally 217 HBcIgG positive patients with solid cancer were included in the study. Anti-HBs positive and negative patients were 119 (54.8%) and 98 (45.2%), respectively. Frequent diagnosis of the patients was lung (28.1%), colorectal (19.4%), breast (17.5%) and hepatobiliary tract cancers (8.3%), respectively. Most of the study population had stage 4 disease (48.8%) and received palliative chemotherapy. When the patients were stratified due to American Gastroenterological Association Institute (AGA) guideline, HBVr risk of chemo regimen was moderate in 21 patients (17.5%), low in 8 patients (3.7%). The majority of the patients were undefined risk group (78.8%). We did not determine any HBVr in the patients who have received different conventional chemotherapy regimens and have different primer tumor site despite all the patients did not receive the prophylactic antiviral drug. [Med-Science 2019; 8(2.000): 418-21]

Abstract Objective There are three major serologic markers for hepatitis B virus (HBV) infection: hepatitis B surface antigen (HBsAg); hepatitis B surface antibody (anti-HBs); and hepatitis B core antibody (anti-HBc). HBV screening programs, however, often test only HBsAg and anti-HBs, missing those individuals who have anti-HBc as the only detectable marker. Isolated anti-HBc can represent chronic infection in which HBsAg is not detectable by serology. We, therefore, investigated the prevalence of isolated anti-HBc in an ethnic community at moderate to high risk for HBV infection. Results Of 7157 Korean American adults in New Jersey, 2736 (38.2%) lacked anti-HBs, potentially susceptible to HBV. Of these 2736 subjects, 771 subjects had anti-HBc. The prevalence of isolated anti-HBc increased with age: 0.8% (age 21–30); 2.4% (age 31–40); 6.05% (age 41–50); 11.7% (age 51–60); 18.3% (age 61–70); and 24.5% (age 71–91). Similarly, the percentage of the individuals with isolated anti-HBc in anti-HBs lacking subjects showed a striking age dependence. We conclude that serologic HBV screening should include anti-HBc to accurately assess the prevalence of HBV exposure. Serologic screening with only HBsAg and anti-HBs may overestimate the prevalence of non-immune population. It can also underestimate the prevalence of HBV and increase the risk of HBV reactivation during immunosuppression.

We conducted a nationwide retrospective analysis of 116 hepatitis B virus (HBV) surface antigen (HBsAg)‐positive patients with diffuse large B‐cell lymphoma (DLBCL) and 278 HBsAg‐negative patients with DLBCL, as a control cohort, who received rituximab‐containing regimens as an induction chemotherapy at 30 Japanese medical centers between January 2004 and December 2014. Hepatitis was defined as an absolute serum alanine aminotransferase (ALT) level of ≥100 U/L. HBV reactivation‐related hepatitis was defined as hepatitis with an absolute serum HBV DNA level of ≥3.3 log IU/mL or an absolute increase of ≥2 log compared with the baseline value. HBsAg‐positive patients were divided into three groups based on anti–HBV prophylactic therapy: no nucleos(t)ide analogue (non–NA, n = 9), lamivudine (LAM, n = 20), and entecavir (ETV, n = 87). The 4‐year cumulative incidence (CI) of hepatitis in HBsAg‐positive and HBsAg‐negative patients was 21.1% and 14.6% (P =.081), respectively. The 4‐year CI of HBV reactivation‐related hepatitis was higher in HBsAg‐positive patients than in HBsAg‐negative patients (8.0% vs 0.4%; P <.001). Among HBsAg‐positive patients, the 4‐year CI of HBV reactivation‐related hepatitis was the highest in the non–NA group (33.3%), followed by the LAM (15.0%) and ETV (3.8%) groups (P <.001). Of note, 3 non–NA patients (33%) and 1 LAM patient (5%) (but no ETV patients) died due to HBV hepatitis. Based on Cox multivariate analysis, HBsAg positivity was not associated with poor overall survival. Prophylactic use of ETV would reduce the occurrence of HBV reactivation‐related hepatitis and mortality in HBsAg‐positive DLBCL patients receiving rituximab‐containing chemotherapy. [ABSTRACT FROM AUTHOR]

Kidney transplant recipients (KTRs) have increased risk for cytomegalovirus (CMV) infection/disease given the necessity of drug‐induced immunosuppression. A comprehensive review of published literature reporting real‐world data on prevention strategies utilized and associated CMV burden outcomes is limited. Such data could help inform future clinical practice and identify unmet needs in CMV management. We conducted a systematic review of observational studies published in Medline or EMBASE from January 2008 to November 2018 to identify current real‐world CMV management approaches, CMV infection/disease risk factors, and outcomes associated with CMV infection. Descriptive statistics and pooled quantitative analyses were conducted. From 1608 records screened, 86 citations, including 69 803 adult KTR, were included. Prophylaxis and preemptive therapy (PET) were predominant approaches among D+/R‐ and R + CMV serostatus transplants, respectively. Valganciclovir and ganciclovir were frequently utilized across CMV risk strata. Despite prevention approaches, approximately one‐fourth of KTR developed CMV infection. Age and D+/R‐ CMV serostatus were consistent risk factors for CMV infection/disease. CMV infection/disease was associated with increased mortality and graft loss. CMV was similarly associated with acute rejection (AR) risk, but with high heterogeneity among studies. Limited data were available on CMV and opportunistic infections (OIs) risk. CMV remains a significant issue. New strategies may be needed to optimize CMV management. [ABSTRACT FROM AUTHOR]

BackgroundThis study aimed to investigate the influence of hepatic artery infusion chemotherapy (HAIC) on hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg) positive patients with primary hepatocellular carcinoma (HCC) as well as evaluate the role of antiviral prophylaxis in these patients.MethodsWe enrolled 170 HBsAg-positive advanced HCC patients receiving HAIC using mFOLFOX regimen, of which 137 patients received antiviral prophylaxis. Risk factors for HBV reactivation were analyzed. The overall survival (OS) from the first application of HAIC were compared between antiviral and non-antiviral groups.ResultsA total of 25 patients (14.7%) developed HBV reactivation after HAIC, of which 16 patients received antiviral treatment and nine patients did not. The incidence of HBV reactivation was 11.7% (16/137) in antiviral group and 27.3% (9/33) in non-antiviral group respectively. No antiviral prophylactic was the only significant risk factor for HBV reactivation (OR=12.35, 95% confidence interval (CI) 4.35–33.33, p

Background: A self‐limited hepatitis B infection can reactivate in patients under immunosuppression or chemotherapy (reappearance of hepatitis B surface antigen (HBsAg) or HBV‐DNA). Exact circumstances of HBV reactivation in patients undergoing liver transplantation (LT) for end‐stage liver diseases (ESLD) unrelated to HBV are unknown, and recommendations on HBV prophylaxis remain unclear. Patients and methods: Among 1273 liver transplants, 168 patients with a self‐limited HBV hepatitis B infection prior to LT were identified from our prospective liver transplant database. Patients with underlying chronic HBV infection and recipients of an anti‐HBc‐positive liver were not included in the analysis. Demographic, laboratory, serological, and virological data were analyzed retrospectively. Appearance of HBsAg or HBV‐DNA was defined as reactivation. Results: The median follow‐up after LT was 12.0 years (0.6‐30.7 years). The rate of HBV reactivation was 0% independent of antiviral prophylaxis (n = 7; 4.2%), the etiology of ESLD, hepatitis C treatment, or the anti‐HBs concentration. The overall patient survival with a history of a self‐limited HBV infection before LT did not significantly differ from the rest of the cohort. Conclusion: Antiviral treatment with nucleos(t)ide analogues post‐liver transplantation in order to prevent HBV reactivation in patients with a resolved self‐limited hepatitis B infection prior to LT seems to be omittable since the main viral reservoir is removed by the hepatectomy. These findings may clarify the current uncertainty in the recommendations regarding the risk of HBV reactivation in patients with self‐limited hepatitis B prior to LT. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the influence of hepatic artery infusion chemotherapy (HAIC) on hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg) positive patients with primary hepatocellular carcinoma (HCC) as well as evaluate the role of antiviral prophylaxis in these patients. Methods: We enrolled 170 HBsAg-positive advanced HCC patients receiving HAIC using mFOLFOX regimen, of which 137 patients received antiviral prophylaxis. Risk factors for HBV reactivation were analyzed. The overall survival (OS) from the first application of HAIC were compared between antiviral and non-antiviral groups. Results: A total of 25 patients (14.7%) developed HBV reactivation after HAIC, of which 16 patients received antiviral treatment and nine patients did not. The incidence of HBV reactivation was 11.7% (16/137) in antiviral group and 27.3% (9/33) in non-antiviral group respectively. No antiviral prophylactic was the only significant risk factor for HBV reactivation (OR=12.35, 95% confidence interval (CI) 4.35–33.33, p<0.001). Patients in antiviral group received more cycles of HAIC compared with non-antiviral group (3.11 ± 1.69 vs 1.75 ± 1.18, p<0.05) at the time of HBV reactivated. Seven of the 25 HBV reactivation patients developed hepatitis. OS in antiviral group was significantly longer than that of non-antiviral group (median 16.46 vs 10.68 months; HR=0.57; 95% CI, 0.36–0.91; p<0.05). Conclusions: HBV reactivation is more prone to occur in the HBsAg-positive HCC patients undergoing HAIC without antiviral prophylaxis. Regular monitoring of HBV DNA and antiviral prophylaxis are suggested to prevent HBV reactivation as well as prolong the OS of these patients. Name of the Trial Register: HAIC Using Oxaliplatin Plus Fluorouracil/Leucovorin for Patients with Locally Advanced HCC. Clinical Trial Registration: https://www.clinicaltrials.gov/ , identifier NCT 02436044 [ABSTRACT FROM AUTHOR]

Summary: The prevention of hepatitis B virus (HBV) reactivation during rituximab treatment for diffuse large B‐cell lymphoma (DLBCL) is important in the HBV‐endemic area. This population‐based study examines the impact of antiviral prophylaxis for DLBCL patients with HBV infections. We identified 3702 adult patients with newly diagnosed DLBCL between 2011 and 2015 receiving R‐CHOP, R‐CVP, CHOP or CVP from the Taiwan Cancer Registry. We further stratified them into three groups: HBsAg‐negative patients (HBV‐negative, N = 2921), HBV carriers who received antiviral prophylaxis (HBV + Px, N = 711), and HBV carriers who did not receive antiviral prophylaxis (HBV + No Px, N = 70). HBV + Px patients were the youngest, and 69·4% received entecavir for antiviral prophylaxis. The median overall survival (mOS) of HBV‐negative and HBV + Px patients was similar (74·23 months and not reached, respectively). However, the mOS of HBV + No Px patients was only 35·61 months (P = 0·0028 compared with HBV + Px patients), indicating that antiviral prophylaxis improves OS in HBsAg‐positive DLBCL patients. The multivariate analysis showed that the HBV status and antiviral prophylaxis was an independent prognostic factor. In conclusion, our population‐based study illustrates the importance of antiviral prophylaxis in HBsAg‐positive DLBCL patients. Under antiviral prophylaxis, the survival of DLBCL patients with HBV infections was comparable to that of HBV‐negative patients. [ABSTRACT FROM AUTHOR]

The role of novel HBV markers in predicting Hepatitis B virus reactivation (HBV-R) in HBsAg-negative/anti-HBc-positive oncohaematological patients was examined. One hundred and seven HBsAg-negative/anti-HBc-positive oncohaematological patients, receiving anti-HBV prophylaxis for >18 months, were included. At baseline, all patients had undetectable HBV DNA, and 67.3% were anti-HBs positive. HBV-R occurred in 17 (15.9%) patients: 6 during and 11 after the prophylaxis period. At HBV-R, the median (IQR) HBV-DNA was 44 (27–40509) IU/mL, and the alanine aminotransferase upper limit of normal (ULN) was 44% (median (IQR): 81 (49–541) U/L). An anti-HBc > 3 cut-off index (COI) plus anti-HBs persistently/declining to p < 0.001)). The detection of highly sensitive (HS) HBsAg and/or HBV-DNA confirmed at >2 time points, also predicts HBV-R (OR (95% CI): 13.8 (3.6–52.6); 50% of positive vs. 7% of negative patients to these markers experienced HBV-R (p = 0.001)). HS-HBs and anti-HBc titration proved to be useful early markers of HBV-R. The use of these markers demonstrated that HBV-R frequently occurs in oncohaematological patients with signs of resolved HBV infection, raising issues of proper HBV-R monitoring.

Abstract Background In Korea, hepatitis B virus (HBV) infection accounts for approximately 65–75% of HBV-related diseases, such as chronic hepatitis and liver cancer, and mother-to-child transmission is presumed to be a major source of the infection. To tackle this issue, the Korean government launched the national Perinatal Hepatitis B Prevention Program (PHBPP) in 2002. This study analyzed the cost-effectiveness of the PHBPP with antiviral prophylaxis compared with the current PHBPP and/or universal vaccination, as well as identified the optimal strategy to eliminate mother-to-child transmission of HBV in Korea. Methods A decision tree model with the Markov process was developed and simulated over the lifetime of a birth cohort in Korea during the year 2014. The current PHBPP providing HBV vaccine and hepatitis B immune globulin to neonates born to HBV positive mothers was compared against two other strategies, universal vaccination of HBV and PHBPP with antiviral prophylaxis, with respect to their costs and health outcomes. The Korean National Health Insurance database was investigated to estimate the costs of HBV-related diseases and utilization of health resources. Costs were assessed from the health care system perspective and converted to 2014 US dollars. Health outcome measures were quality-adjusted life years (QALYs) and number of HBV-related diseases and deaths. Both costs and QALYs were discounted at 5%, following the recommendation of the Health Insurance Review & Assessment Service in Korea. The incremental cost-effectiveness ratio (ICER) obtained from the analysis was evaluated using the willingness-to-pay (WTP) in the Korean society. Results PHBPP with antiviral prophylaxis in Korea was cost-effective compared with the current PHBPP. An introduction of antiviral prophylaxis to pregnant women with a high viral load of HBV averted 13 HBV-related deaths per 100,000 people and saved 82 QALYs in total (ICER: $16,159/QALY). Conclusions Considering that WTP in Korea is $29,000, PHBPP with antiviral prophylaxis appears to be a cost-effective strategy. To further decrease the burden of perinatal hepatitis B in Korea, adding antiviral prophylaxis to PHBPP is recommended.

Abstract Background The risk of Hepatitis B virus (HBV) reactivation in patients with different hematological malignancy except lymphoma were rarely known before. Methods A total of 1962 patients with hematological malignancy were enrolled and followed-up at the National Taiwan University Hospital between 2008 and 2013. The clinical characteristics, HBV serology, and laboratory data were retrospectively reviewed and analyzed. Results A total of 1962 patients comprising 1048 men and 914 women were studied. The median age of the patients was 55 years (range, 15–97 years). Chronic HBV carriage was documented at diagnosis of hematological malignancy in 286 (14.6%) patients. A total of 171 (59.8%) of the 286 HBV carriers received primary prophylaxis with anti-HBV agents. Of the HBV carriers, 97 (33.9%) developed hepatitis B reactivation during or after chemotherapy, including 59 patients who had discontinued antiviral therapy. The incidence of hepatitis B reactivation among patients with hematological malignancy and HBV carriage was 10.4 per 100 person–years. A multivariate analysis revealed hepatocellular carcinoma (p

The aim of the study was to identify care home characteristics associated with reported care home influenza outbreaks and factors associated with increased transmission of influenza-like illness (ILI) in care homes in Cheshire and Merseyside during the 2017–2018 influenza season. This is a matched case-control study comparing characteristics between care homes with and without a declared influenza outbreak and a retrospective risk factor analysis of care home residents with ILI. Routinely collected outbreak surveillance data on symptomatic residents and staff, antiviral prophylaxis and influenza vaccination history, which were reported to Public Health England, were extracted from health protection electronic records. Further care home characteristics were extracted from the Care Quality Commission (CQC) website. Care homes with declared influenza outbreaks were matched with care homes without outbreaks. Chi-squared tests and logistic regression were used to examine associations between care home factors and ILI. There were no significant differences in characteristics between 77 care homes with declared influenza outbreaks and 77 matched care homes without outbreaks. Of 2,744 residents from the homes with a declared outbreak, 644 (24%) developed an ILI. The care home risk factors were having a low CQC score and activation of antiviral prophylaxis and the protective factors were having higher numbers of residents, specializing in dementia care and having the highest CQC score. Significantly more cases occurred in residential homes than in nursing homes, in homes with lower CQC scores and in homes where eligible residents were given antiviral prophylaxis. In homes with declared outbreaks, certain characteristics including activation of antiviral prophylaxis were associated with an increased risk of ILI. Further research is needed, particularly focussing on temporality between provision of prophylactic antivirals and the onset of ILI. • Homes with and without declared influenza outbreaks had similar characteristics. • One in four residents from homes with declared outbreaks had influenza-like illness. • Low Care Quality Commission (CQC) scores and antiviral prophylaxis were associated with more influenza. • More data are needed on the timing of antiviral prophylaxis administration and cases. • Protective factors included large homes, high CQC scores and dementia specialism. [ABSTRACT FROM AUTHOR]