Modelling the Prevalence of Hepatitis B Towards Eliminating It as a Major Public Health Threat in China

Background: The World Health Organization (WHO) requires a reduction in the prevalence of hepatitis B virus (HBV) surface antigen (HBsAg) in children to 0.1% by 2030, a key indicator for eliminating viral hepatitis as a major public health threat. Whether and how China can achieve this target remains unknown, although great achievements have been made. We aimed to predict the decline of HBsAg prevalence in China and identify key developments needed to achieve the target.Methods: An age- and time-dependent dynamic compartmental model was constructed based on the natural history of HBV infection and the national history and current status of hepatitis B control. The model was run from 2006 to 2040 to predict the decline of HBsAg prevalence under three scenarios including maintaining current interventions (status quo), status quo + peripartum antiviral prophylaxis (recommended by WHO in 2020), and scaling up available interventions.Results: Under the status quo, HBsAg prevalence would decrease steadily in all age groups, but the WHO’s target of 0.1% prevalence in children aged < 5 years would not be achieved until 2037. The results are robust according to sensitivity analyses. Under the status quo + antiviral prophylaxis, the HBsAg prevalence of children aged < 5 years would significantly decrease with the introduction of peripartum antiviral prophylaxis, and the higher the successful interruption coverage is achieved, the more significant the decline. However, even if the successful interruption coverage reaches 90% by 2030, the 0.1% prevalence target would not be met until 2031. Under the scaling up available interventions, combined with scale-up of current interventions, the WHO’s 0.1% target would be achieved on time or one year in advance if peripartum antiviral prophylaxis is introduced and the successful interruption coverage is scaled up to 80% or 90% by 2030, respectively.Conclusions: It is difficult for China to achieve the WHO’s target of 0.1% HBsAg prevalence in children by 2030 by maintaining current interventions. Peripartum antiviral prophylaxis may play an important role to shorten the time to achieve the target. A comprehensive scale-up of available interventions including peripartum antiviral prophylaxis will ensure that China achieves the target on schedule.

High Risk of Viral Reactivation in Hepatitis B Patients with Systemic Lupus Erythematosus

HBV reactivation (HBVr) can occur in hepatitis B surface antigen (HBsAg)-positive and negative patients. Here, we determined the incidence of HBVr and its related hepatitis in patients with systemic lupus erythematosus (SLE). From 2000 to 2017, 3307 SLE cases were retrospectively reviewed for episodes of hepatitis. The incidence, long-term outcomes and risk factors associated with HBVr, including HBsAg reverse seroconversion (RS) were analyzed. Among them, 607 had available HBsAg status. Fifty-five (9.1%) patients were positive for HBsAg and 63 (11.4%) were HBsAg-negative/antibody to hepatitis B core antigen (anti-HBc)-positive (resolved hepatitis B infection, RHB). None of them received antiviral prophylaxis before immunosuppressive treatment. During a mean 15.4 years of follow-up, 30 (54.5%) HBsAg-positive patients developed HBVr and seven (23.3%) died of liver failure, whereas only two (3.2%) RHB cases experienced HBsAg reverse seroconversion (RS). Multivariate logistic regression analysis showed that age ≥ 40 years at diagnosis of SLE (HR 5.30, p < 0.001), receiving glucocorticoid-containing immunosuppressive therapy (HR 4.78, p = 0.003), and receiving glucocorticoid ≥ 10 mg prednisolone equivalents (HR 3.68, p = 0.003) were independent risk factors for HBVr in HBsAg-positive patients. Peak level of total bilirubin ≥ 5 mg/dL during HBVr was an independent factor of mortality (p = 0.002). In conclusion, the risk of HBVr was associated with glucocorticoid daily dose. Antiviral prophylaxis is mandatory for SLE patients diagnosed at age of ≥40 years who receive ≥ 10 mg daily dose of oral prednisone or equivalent.

Prevention of viral infections in families of recipients of solid organs

Current COVID-19 pandemic demands improvements in antiviral prophylaxis. Tyloron, as biological interferon activator, has been synthesized in the 70th of previous century. We used Tyloron in 60 patients – relatives and partners living together with solid organ transplant recipients – in autumn 2020, during second wave of the SARS-CoV‑2 pandemic. Results were compared with 60 patients used other means of antiviral prophylaxis. In patients taking Tyloron the number of febrile episodes was significantly lower (р < 0.02).

Risk of HBV Reactivation in Patients With Resolved HBV Infection Receiving Anti-CD19 Chimeric Antigen Receptor T Cell Therapy Without Antiviral Prophylaxis

BackgroundChimeric antigen receptor (CAR) T-cell therapy has emerged as a novel treatment modality for hematologic malignancies and is predicted to experience widespread use in the near future. However, not all risks associated with this novel approach are well defined. There are few data in the risk of HBV reactivation and limited experience in management in patients with resolved HBV infection who undergo CAR-T cell therapy.MethodsWe performed a post-hoc analysis of a prospective clinical trial of anti-CD19 CAR-T (CART19) cell therapy in patients with relapsed or refractory (r/r) B-cell malignancies, and aimed at exploring the actual risk of HBV reactivation in a cohort of patients with resolved HBV infection receiving CART19 cell therapy in the absence of antiviral prophylaxis.ResultsIn this study, we investigated the risk of HBV reactivation after CART19 cell therapy in 30 consecutive patients with B-cell malignancies and resolved HBV infection without antiviral prophylaxis, in the Tongji Hospital of Tongji University. In this cohort, two patients developed HBV reactivation 2 months and 14 months after CAR-T cell infusion, respectively, the latter of whom developed severe hepatitis. These findings showed that the incidence of HBV reactivation was 6.67% (95% CI, 0.8–22.1). Specifically, none of the 21 patients who were HBsAb positive (0.0%) versus two of nine patients who were HBsAb negative (22.2%) experienced HBV reactivation (p = 0.03), suggesting HbsAb seronegativity at baseline is a possible risk factor in this population. Although use of tocilizumab or corticosteroids has been associated with increased risk of HBV reactivation, none of the patients who received these agents had HBV reactivation in this study.ConclusionThis is the first and largest study to assess the true incidence of HBV reactivation in patients with resolved HBV infection receiving CART19 cell therapy without antiviral prophylaxis. This study highlights that this population are at risk of developing HBV reactivation and indicates that close monitoring of HBV DNA is required in the absence of antiviral prophylaxis. In addition, antiviral prophylaxis is recommended in the HBsAb-negative subpopulation.

Liver failure from delayed hepatitis B reactivation in anti-HBc-positive patient following rituximab for B-cell lymphoma

A 93-year-old man was admitted with 1 week of frank jaundice and abdominal pain. His medical history included diffuse large B-cell lymphoma treated with rituximab and cyclophosphamide, hydroxydaunomycin, oncovin and prednisolone (R-CHOP) chemotherapy 10 months prior. His investigations revealed marked hyperbilirubinemia with a total bilirubin of 355 μmol/L, along with a 17-fold elevation in alanine transaminase and impaired hepatic synthetic function. He tested hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (HBsAb) negative, hepatitis B core antibody (HBcAb) positive and had elevated hepatitis B virus DNA level at 13 691 IU/L. This was in the setting of radiological evidence of suspected cirrhosis. He was later found to have tested positive for HBcAb and negative for HBsAg and HBsAb prior to chemotherapy, but had not received antiviral prophylaxis. He was diagnosed with fulminant hepatitis secondary to delayed hepatitis B reactivation in the setting of rituximab. Hepatitis B reactivation and the role of screening and antiviral prophylaxis in isolated HBcAb-positive patients is reviewed.

Association between Antiviral Prophylaxis and Cytomegalovirus and Epstein–Barr Virus DNAemia in Pediatric Recipients of Allogeneic Hematopoietic Stem Cell Transplant

Background: Epstein–Barr virus (EBV) and cytomegalovirus (CMV) infections can have serious consequences during the period of aplasia and lymphopenia following hematopoietic stem cell transplantation (HSCT). Large pediatric cohort studies examining the effect of antiviral prophylaxis against these viruses are scarce. The present study aimed to analyse the potential effect of antiviral prophylaxis (acyclovir and famciclovir) on active post-transplant EBV and CMV infection in a pediatric cohort of allogeneic HSCT recipients. Methods: We used data from the TREASuRE cohort, consisting of 156 patients who had a first allogeneic HSCT, enrolled in four pediatric centers in Canada between July 2013 and March 2017. Follow-up was performed from the time of transplant up to 100 days post-transplant. Adjusted hazard ratio (HR) with 95% confidence intervals (CI) for the association between antiviral prophylaxis with acyclovir and/or famciclovir and EBV and CMV DNAemia was estimated using multivariate Cox regression models. Results: The post-transplant cumulative incidence of EBV and CMV DNAemia at 100 days of follow-up were, respectively, 34.5% (95% CI: 27.6–42.6) and 19.9% (95% CI: 14.5–27.1). For acyclovir, the adjusted hazard ratio (HR) for CMV and EBV DNAemia was 0.55 (95% CI: 0.24–1.26) and 1.41 (95% CI: 0.63–3.14), respectively. For famciclovir, the adjusted HR were 0.82 (95% CI: 0.30–2.29) and 0.79 (95% CI: 0.36–1.72) for CMV and EBV DNAemia, respectively. Conclusion: The antivirals famciclovir and acyclovir did not reduce the risk of post-transplant CMV and EBV DNAemia among HSCT recipients in our pediatric population.

Persistent Neutropenia after ABOi Kidney Transplantation: A Case Report

Post-transplant neutropenia (PTN) is frequently reported in the first-year after transplantation. Although prevalence and clinical consequences are widely described, there are no guidelines to manage diagnosis and treatment. We report here a case of persistent PTN occurred in a patient undergoing a kidney transplant from an AB0-incompatible living donor. The desensitization protocol consisted of Rituximab administration and immunoadsorption while the pre-transplant protocol, which was initiated 14 days before the transplant, included Tacrolimus, Mofetil Mycophenolate (MMF), antimicrobial and antiviral prophylaxis. Induction therapy consisted of anti-thymocyte globulins and steroids, while maintenance after transplantation consisted of steroid, tacrolimus and MMF. When the first occurrence of leukopenia was observed six weeks after the transplant, firstly antimicrobial/antiviral prophylaxis was stopped and later also MMF treatment was interrupted but severe neutropenia relapsed after MMF resuming treatment. Immunological and virological causes were excluded. The patient was treated with Filgrastim. Bone marrow biopsy, which was performed to exclude a hematological cause of severe persistent neutropenia, revealed a bone marrow hypoplasia with neutrophils maturation interrupted at the early stages. This case highlights the need to establish diagnostic and therapeutic guidelines for PTN which take in consideration all the therapeutic steps including the pre-transplant phase in particular in the context of AB0i where immunosuppression is more consistent.