Hepatitis B Virus Prophylaxis Research Articles

Evaluation of the frequency of hepatitis b virus reactivation and the importance of hepatitis b prophylaxis in hematology patients receiving immunosuppressive therapy: a single-center study

Aims: The aim of this study was to evaluate the rate of hepatitis B virus reactivation (HBVr) in hematology patients receiving immunosuppressive therapy in our center and the clinical characteristics of patients with HBVr. We will also investigate the importance of effective prevention of this potentially life-threatening event and management of hepatitis B virus (HBV) prophylaxis. Methods: In this study, hepatitis B prophylaxis and its effects on patients over 18 years of age receiving immunosuppressive therapy in the hematology clinic were analyzed. 122 patients were included in the study. The HBV markers of the patients were determined by the chemiluminescence method. In the study, HbsAg(+) and isolated antiHbc IgG-positive patients received prophylactic antiviral treatment. The differential diagnosis of HBV reactivation and the criteria determined to define HBV reactivation were performed. Clinical characteristics and descriptive information of patients receiving HBV prophylaxis were analyzed using SPSS 25.0. Results: The median age of 122 patients (59.8% male) was 58 years. It was determined that five HbsAg-positive patients had no prior follow-up and did not receive antiviral treatment. 117 patients had isolated anti-HBc IgG positivity. The median duration of prophylaxis was 15 (9- 21.25) months, and the total follow-up period was 19.5 (11.75- 30.25) months. 81.1% of the patients received regular HBV prophylaxis treatment; 59% of them received entecavir, and the rest received tenofovir disoproxil. Bone marrow transplantation was performed in 25 patients. HBV reactivation was detected in only 4 patients (3.3%); one of these patients had received allogeneic and one autologous bone marrow transplantation; and three patients had received chemoimmunotherapy including Rituximab. The diagnoses of the patients with HBVr were acute myeloid leukemia, lymphoma, and chronic lymphocytic leukemia. During the follow-up period, 29 patients (23.8%) died due to their primary disease, but there were no deaths due to HBV reactivation. Conclusion: The data obtained in this study show that effective hepatitis B prophylaxis treatment is successful in preventing HBV reactivation in hematology patients. HBVr was observed in four patients who did not take HBV prophylaxis medication regularly.

Single-cell analysis reveals HBV-specific PD-1+CD8+ TRM cells in tumor borders are associated with HBV-related hepatic damage and fibrosis in HCC patients

Immune checkpoint blockade (ICB) treatment of hepatocellular carcinoma (HCC) patients with hepatitis B virus (HBV) infection may activate viral-specific T cells to attack HBV infected hepatocytes and thus induce immune-related liver injury. Therefore, it is important to deeply understand the impacts of HBV infection on HCC immune microenvironment in order to better design effective immunotherapies for HBV+ (HBV infected) HCC patients. Here, We performed cytometry by time-of-flight (CyTOF) analyses to characterize the distinct immune compositions of HCC tumors, tumor borders, and their associations with HCC/HBV related clinical characteristics. We identified 31 distinct immune clusters and found significant associations between immune signatures with clinicopathological features of HCC. We further revealed the HBV infection had more effects on shaping immune compositions in tumor borders than in tumors, with the significant enrichment of HBV-specific PD-1+CD8+ tissue-resident memory T (TRM) cells in tumor borders of HBV+ patients. We confirmed this subset with a more exhausted phenotype and respond more actively under anti-PD-L1 treatment, suggesting its involvement in immune-related liver injury induced by ICB treatment to HBV+ HCC patients. Our study shows it may be necessary to consider antiviral prophylaxis for HBV+ HCC patients receiving ICB treatment.

Hepatitis B Virus in West African Children: Systematic Review and Meta-Analysis of HIV and Other Factors Associated with Hepatitis B Infection.

While Hepatitis B virus (HBV) and the human immunodeficiency virus (HIV) are endemic in West Africa, the prevalence of HBV/HIV coinfection and their associated risk factors in children remains unclear. In this review, we sought to assess HBsAg seroprevalence among 0- to 16-year-olds with and without HIV in West African countries and the risk factors associated with HBV infection in this population. Research articles between 2000 and 2021 that reported the prevalence of HBV and associated risk factors in children in West Africa were retrieved from the literature using the Africa Journals Online (AJOL), PubMed, Google Scholar, and Web of Science databases as search tools. StatsDirect, a statistical software, was used to perform a meta-analysis of the retained studies. HBV prevalence and heterogeneity were then assessed with a 95% confidence interval (CI). Publication bias was evaluated using funnel plot asymmetry and Egger's test. Twenty-seven articles conducted across seven West African countries were included in this review. HBV prevalence among persons aged 0 to 16 years was 5%, based on the random analysis, given the great heterogeneity of the studies. By country, the highest prevalence was observed in Benin (10%), followed by Nigeria (7%), and Ivory Coast (5%), with Togo (1%) having the lowest. HBV prevalence in an HIV-infected population of children was (9%). Vaccinated children had lower HBV prevalence (2%) than unvaccinated children (6%). HBV prevalence with a defined risk factor such as HIV co-infection, maternal HBsAg positivity, undergoing surgery, scarification, or being unvaccinated ranged from 3-9%. The study highlights the need to reinforce vaccination of newborns, screening for HBV, and HBV prophylaxis among pregnant women in Africa, particularly in West Africa, to achieve the WHO goal of HBV elimination, particularly in children.

High-potency nucleos(t)ide analogues alone or plus immunoglobulin for HBV prophylaxis after liver transplantation: a meta-analysis.

The optimum prophylactic regimen against hepatitis B virus (HBV) recurrence after liver transplantation (LT) in HBV-infected patients is uncertain but of great clinical relevance. New evidence suggests that hepatitis B immunoglobulin (HBIG)-free approach would become a reasonable choice in the era of high-potency nucleos(t)ide analogues (HPNAs). We aimed to provide robust estimates for long-term survival and HBV recurrence in patients receiving different HBV-prophylaxis strategies after LT. We did a systematic review and meta-analysis using both pseudo-individual patient data recovered from included studies (IPDMA) and conventional trial-level aggregate data meta-analysis (ADMA). Hazard ratios (HRs) were calculated using different Cox proportional hazard models accounting for inter-study heterogeneity. ADMA was conducted to pool outcomes at specific time points. A total of 16 studies involving 7897 patients and 41 studies involving 9435 were eligible for IPDMA and AMDA, respectively. Cumulative HBV recurrence rate and overall survival (OS) at 1, 3, 5 and 10years post-LT were 0.3%, 0.9%, 1.2%, 1.7% and 95.6%, 89%, 86.4%, 86.4% in the HPNAs (i.e., entecavir and tenofovir) + HBIG combination group vs. 0.6%, 0.6%, 1.2%, 1.7% and 94.5%, 86.8%, 84.8%, 81.2% in the HPNAs monotherapy group (HR 1.20, 95% CI 0.56-2.60, p = 0.64; HR 1.09, 95% CI 0.70-1.69, p = 0.72), respectively. The results were compatible with AMDA. A similar HBV recurrence and overall survival were found in patients who used HPNAs (mainly entecavir) monotherapy as in those who received a combination of HPNAs and HBIG. These findings address concerns regarding the safety and effectiveness of HPNAs monotherapy.

Overlooked complication of Cushing's syndrome: Reactivation of hepatitis B.

Individuals infected with hepatitis B virus (HBV) are at increased risk of reactivation when they receive immunosuppressive therapies. Although exogenous corticosteroid use as immunosuppressive therapy is elaborated in current guidelines on HBV reactivation, Cushing's syndrome (CS) with endogenous hypercortisolemia is not addressed. We aimed to investigate the prevalence of HBV infection and discuss the necessity of antiviral prophylaxis in patients with CS as in other immunosuppressed patients. We included 72 patients with CS (Adrenocorticotropic hormone (ACTH) dependent or independent) who were screened for HBV between 2016 and 2021. Patients were categorized into three groups: overt, mild autonomous cortisol secretion (MACS), and remission according to the cortisol burden. Changes in patients' HBV serology and clinical findings over time were analyzed retrospectively. Twenty-six patients had overt hypercortisolism, 18 had mild autonomous cortisol secretion and 28 patients were in remission. Nineteen (26.3%) patients were anti-HBc IgG positive, 4 of them were chronic HBV and 15 were isolated anti-HBc IgG positive. HBsAg was positive in four (5.5%) of the patients, who were all compatible with inactive chronic HBV. While two patients developed HBV reactivation, HBV flare was observed in one patient. Since it is not always possible to achieve rapid remission in CS and these patients have long-term hypercortisolemia, we suggest that consensus should be reached on HBV serological assessment, standardization of follow-up, and planning of HBV prophylaxis in required instances in patients with CS especially in regions with a high prevalence of HBV infection.

Management of hepatitis B virus prophylaxis in patients treated with disease-modifying therapies for multiple sclerosis: a multicentric Italian retrospective study

BackgroundPatients with multiple sclerosis (MS) often receive disease-modifying therapies (DMTs) that can expose them to reactivation of potential occult hepatitis B virus (HBV) infection (pOBI). We aimed to evaluate the MS Centers behavior regarding HBV screening and prophylaxis in a large cohort of MS patients receiving anti-CD20 or cladribine.MethodsRetrospective, multicentric study recruiting Italian MS patients treated with rituximab, ocrelizumab and cladribine.ResultsWe included 931 MS patients from 15 centers. All but 38 patients performed a complete HBV screening. Patients’ age > 50 years was significantly associated with no history of vaccination and HBsAb titres < 100 mIU at baseline (p < 0.001). No significant correlation was found between post-vaccination HBsAb titres and type of treatment (p = 0.5), pre-or post-therapy vaccination (p = 0.2) and number of previous DMTs (p = 0.2). Among pOBI patients (n = 53), 21 received antiviral prophylaxis, while only 13 had HBV DNA monitoring and 19 patients neither monitored HBV DNA nor received prophylaxis.ConclusionsBaseline HBV screening in patients receiving anti-CD20 and cladribine is a consolidated practice. Nonetheless, HBV vaccination coverage is still lacking in such population and age is a significant factor associated with low HBV protection. Rituximab, ocrelizumab and cladribine did not impair HBV vaccine response. Almost 35% of pOBI patients fail to receive HBVr prevention. Management of HBV prophylaxis could be improved in MS patients and further prospective studies are needed to assess the effectiveness of prophylactic strategies in such patients.

Evaluation of Hepatitis B screening and reactivation in patients receiving rituximab containing chemotherapy: A single‐centre study

Hepatitis B virus (HBV) infection is a worldwide distributing viral disease. Hepatitis caused by HBV reactivation may progress to chronic illness and associated with increased risk of hepatic failure and hepatocellular cancer. Rituximab (RTX) is an immunosuppressive agent, is particularly used in the treatment of non-Hodgkin's Lymphoma. Patients have significant risk for HBV reactivation following chemotherapy with a RTX-containing regimen. This study aimed to determine the HBV screening manner and reactivation rates in patients with haematological neoplasm following chemotherapy including Rituximab. This is a single-centered retrospective cohort study. A total of 331 adults with haematological disorders who received chemotherapy regimen including RTX between years of 2006 and 2016 were enrolled. Patients who experienced reactivation were evaluated. Only 130 of 331 patients were screened appropriately for HBV infection for 10-year period. We found 18 patients were Hepatitis B surface antigen (HBsAg) (+) and 16 (88.8%) of them received antiviral prophylaxis. Among screened patients, 27 were HBsAg (-)/AntiHBc (+) and only 10 (37%) of them received HBV prophylaxis. In total, nine patients experienced reactivation, six were from screened and three were from unscreened group. Incomplete screening and inappropriate prophylaxis may result in HBV reactivation in patients under RTX-based chemotherapy and related complications such as death.

Hepatitis B Virus Seropositivity in Chronic Myeloid Leukemia Patients Receiving Tyrosine Kinase Inhibitors: Preliminary Results of a Single-Center Cross-Sectional Study

Background: Hepatitis B virus (HBV) infection is a global public health issue, and Turkey is intermediately endemic with 4.5% and 30.6% HbsAg and anti-HBc IgG prevalences, respectively. The HBV infection can be problematique in patients (pts) with hematological malignancies. Tyrosine kinase inhibitors (TKIs) are the mainstay of chronic myeloid leukemia (CML) management, and screening of CML pts for HBV prior to TKI initiation and the management of isolated anti-HBc IgG positivity among these pts are controversial.Aim: To evaluate the frequency and outcome of HbsAg and anti-HBc IgG positivity in CML pts receiving TKIs.Patients and methods: Seventy-four pts with CML in chronic phase (CML-CP) were tested for HBV markers (HbsAg, anti-Hbs, anti-Hbc IgG, HBV DNA) and serum alanine aminotransferase (ALT) levels out of a total of 240 pts as a part of an ongoing study. Pts' characteristics, TKI therapies and durations, response rates, and follow-up periods were noted retrospectively.Results: Pts' characteristics are summarized in Table 1. Fifty-six pts received imatinib (IM) and nilotinib (NIL) was administered in one patient as first-line treatments, whereas the remaining 17 pts had two or more lines of TKI. Median duration of follow-up was 104 months (mos) (range, 3-215 mos). Only one patient was screened for HBV prior to TKI therapy. The median time from TKI initiation to HBV screening was 98 mos (range, 2-179 mos).Fourty-three pts were either HBV naive or anti-Hbs negative. Nineteen pts had anti-Hbc IgG positivity, of whom 10 were also positive for anti-Hbs. Among anti-Hbc IgG positive cases, HBV DNA was negative in twelve pts, and the HBV DNA results of the remaining 7 cases are still pending. None of the pts with isolated anti-Hbc IgG positivity received antiviral prophylaxis for HBV. Four pts (5%) had elevated ALT levels at the time of analysis. One of these pts was HbsAg positive (ALT: 65 IU/ml) (Table 2, case 1); the other was anti-Hbc IgG positive but had negative anti-Hbs and HBV DNA (ALT: 54 IU/ml) receiving IM, whereas the remaining two were HBV negative. Of these two cases, one had grade I (ALT: 57 IU/ml) and the other had grade II (ALT: 101 IU/ml) hepatotoxicity most probably due to dasatinib and NIL, respectively.Two pts were HbsAg positive, and the clinical features of these cases are shown in Table 2. First case had elevated ALT levels (174 IU/ml), positive HbeAg and high HBV DNA which were detected one mo after IM initiation. Tenofovir was started and he had decline in HBV DNA. The patient is still under IM with MMR. The other case experienced HBV reactivation 28 months after IM therapy. With lamivudine treatment, HBV DNA became negative and he is still under IM maintaining MMR.Discussion: The risk of HBV reactivation under TKI therapy and thus, the necessity of screening for HBV prior to TKI initiation are still debating. HBV screening before TKI therapy is not recommended in the ESMO and ELN guidelines, whereas the most recent NCCN guideline and EMA document recommended testing for HBV infection before TKI administration due to some case reports of HBV reactivation after TKI initiation. In our patient cohort the percentages of HbsAg and anti-Hbc IgG positivities were 3% and 26% among the tested cases which were consistent with the prevalences for our general population. Although the nature of our study is cross-sectional and the results are preliminary, the risk of HBV reactivation with TKI use seems to be low in pts with resolved HBV infection and with isolated anti-Hbc IgG positivity and negative HBV DNA among our cohort. Longitudinal studies with serial testing for HBV markers are needed in order to answer these questions in CML pts receiving TKI therapy. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Low Risk for Viral Reactivation during Induction for Acute Myeloid Leukemia in Hepatitis B Silent Carriers Who Are Negativefor Hepatitis B Surface Antigen

Introduction: Latent hepatitis B virus (HBV) infection is a well-recognized risk factor for viral reactivation and life-threatening hepatitis during chemotherapy. Chronic HBV carriers, identified by the presence of hepatitis B antigen (HBsAg) in their serum, have a well-established high risk for reactivation. Patients, exposed to HBV, who have not become true carriers [HBsAg-negative, but anti-hepatitis B core antigen (HBc)-positive] are usually considered to have a “resolved” HBV infection. Current recommendations state that during chemotherapy all patients exposed to HBV in the past are to receive anti-HBV prophylaxis. However, these recommendations are based on data mainly driven from unselected series of cancer patients previously exposed to HBV. It has been clearly demonstrated that HBV reactivation is common in cases where immune suppressive therapy is applied (e.g., patients treated with corticosteroids and/or rituximab or those undergoing stem cell transplantation). Information regarding the incidence and risk factors of HBV reactivation in patients treated for acute myeloid leukemia (AML) is scarce. While some data support prophylaxis for chronic HBV carriers (HbSAg-positive) during chemotherapy for AML, it remains debatable whether this approach is required in AML patients with “resolved” HBV infection undergoing intensive chemotherapy.Methods: The current study reviewed medical files of 1200 patients who were diagnosed with AML between the years 2000-2017 and treated in three large hematology departments in Israel - at the Rambam Health Care Campus, Tel Aviv Sourasky Medical Center and Shaare Zedek Medical Center. Clinical characteristics and laboratory data were retrospectively analyzed. Each patient, diagnosed with AML, was tested for HbSAg, HbSAb, anti-HBc, anti-hepatitis C virus (HCV). Only patients who had not received prophylaxis with anti-HBV agents were included in the analysis.Results: A total of 38 patients with “resolved” HBV infection at the time of leukemia diagnosis were identified, including 15 females (39.5%) and 23 males (60.5%), with a median age of 59.5 years (range 35-80). Six (15.7%) patients were diagnosed with AML secondary to myelodysplastic syndromes (MDS). The following induction regimens were used: daunorubicin + cytarabine (“7+3”) in 34 patients (89.5%), clofarabine in two patients, and high-dose cytarabine (HIDAC) in two patients. Nine patients received re-induction with “7+3”. Twenty seven patients (71%) received consolidation - 26 with HIDAC and one with clofarabine (Table 1). Within 90 days following induction + consolidation therapy, no HBV reactivation was documented in any of the 38 patients. There was a mild and asymptomatic elevation in the levels of hepatocellular liver enzymes (up to 2.5 times the upper limit of normal) in some patients, which could also be attributed to other causes, such as drugs, sepsis, etc. In our cohort of patients, overall survival (OS) was identical to that observed in historical AML patients from our medical centers who were not HBV carriers (Fig. 1).Conclusions: AML patients with previous HBV infection (HBsAg-negative and anti-HBc-positive) undergoing intensive chemotherapy are not at an increased risk for virus reactivation. In the current study, none of the 38 patients had HBV reactivation, suggesting that omission of anti-HBV prophylaxis during induction and consolidation chemotherapy could be considered in select AML patients. Notably, two groups of AML patients with a higher risk of HBV reactivation, i.e., recipients of allogeneic stem cell transplantation and HbSAg-positive patients, were not included in the present study and the conclusions drawn are not applicable to these patient subsets. Larger studies are warranted to explore the role of HBV prophylaxis in “silent” carriers. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Treatment or Prophylaxis against Hepatitis B Virus Infection in Patients with Rheumatic Disease Undergoing Immunosuppressive Therapy: An Update.

Chronic hepatitis B virus (HBV) flares or reactivations are serious causes of morbidity or mortality in rheumatologic patients undergoing immunosuppressive therapy. The recent insights in the pathogenesis of rheumatic diseases led to the use of new immunosuppressive therapies indicated in case of failure, partial response, or intolerance of conventional synthetic disease-modifying anti-rheumatic drugs. Based on these premises, this review examines and discusses the main rheumatologic treatments that could require the initiation of prophylactic treatment or close monitoring of occult HBV infection in patients beginning antiviral therapy at the first signs of HBV reactivation, or antiviral treatment in chronic HBV-infected patients. We searched for relevant studies published in the last five years. Studies suggested that the presence of HBV infection is common in rheumatic patients and HBV reactivation during these immunosuppressant treatments is quite frequent in these kinds of patients. Therefore, before starting an immunosuppressive therapy, patients should be screened for HBsAg, anti-HBs, and anti-HBc and, on the basis of markers positivity, they should be carefully characterized for HBV infection phases. In conclusion, screening of HBV infection in patients undergoing immunosuppressive therapy with subsequent HBV monitoring, prophylaxis or treatment consistently reduces the risk of clinical consequences.

Pre-transplant donor HBV DNA+ and male recipient are independent risk factors for treatment failure in HBsAg+ donors to HBsAg- kidney transplant recipients

BackgroundIn order to reduce the burden on organ shortage around the world, using potential infectious donor might be an option. However, scarce evidences have been published on kidney transplantation (KTx) from hepatitis B surface antigen (HBsAg) + donors to HBsAg- recipients [D (HBsAg+)/R(HBsAg-)] without hepatitis B virus (HBV) immunity. Here, we reported the results of D(HBsAg+/HBV DNA- or +)/R(HBsAg-) living KTx recipients with or without HBV immunity.MethodsWe retrospectively identified 83 D(HBsAg+)/R(HBsAg-) living KTx recipients, and 83 hepatitis B core antibody (HBcAb) + living donors to HBcAb- recipients [D(HBcAb+)/R(HBcAb-)] were used as control group by reviewing medical archives and propensity score matching. Treatment failure (defined as any HBV serology conversion, liver injury, graft loss, or recipient death) is the primary endpoint.ResultsTwenty-four donors (28.9%) were HBV DNA+, and 20 recipients had no HBV immunity in the D(HBsAg+)/R(HBsAg-) group pre-transplantation. HBV prophylaxis was applied in all D(HBsAg+)/R(HBsAg-) recipients, while none was applied in the D(HBcAb+)/R(HBcAb-) group. We observed a significant higher treatment failure in D(HBsAg+)/R(HBsAg-) than D(HBcAb+)/R(HBcAb-) group (21.7% vs. 10.8%, P < 0.001). Interestingly, no significant difference was found between groups on HBV seroconversion, liver and graft function, rejection, infection, graft loss, or death. However, 2/20 recipients without HBV immunity in the D(HBsAg+)/R(HBsAg-) group developed HBV DNA+ or HBsAg+, while none observed in the D(HBcAb+)/R(HBcAb-) group. HBV DNA+ donor and male recipient were significant risk factors for treatment failure.ConclusionD(HBsAg+)/R(HBsAg-) should be considered for living kidney transplantation, but with extra caution on donors with HBV DNA+ and male candidates.

Significance of detectable hepatitis B virus DNA in liver allograft tissue in long-term follow-up of liver transplant recipients.

Background and Aim:The objective of this study was to evaluate the long-term presence of hepatitis B virus (HBV) DNA in the liver grafts of liver transplant patients who received hepatitis B immunoglobulin (HBIg) plus oral antiviral hepatitis B virus prophylaxis and had negative HBV serum markers.Materials and Methods:Patients aged 18 years or older who underwent liver transplantation for HBV-related liver disease, had negative serum viral markers, and had a liver biopsy at least 3 years after liver transplantation were eligible for this study. Clinical, serological, and pathological data were retrospectively obtained from medical records. The HBV DNA of liver biopsy specimens was assessed using the polymerase chain reaction technique.Results:A total of 150 patients were included. A positive HBV DNA result was seen in 18 (12%) of the liver biopsies. The presence of intrahepatic HBV DNA was not associated with pre-transplantation serum viral markers, type of pre- or post-transplantation antiviral treatment, or post-transplantation immunosuppressive treatment.Conclusion:The findings suggest that while treatment with HBIg plus oral antiviral as post-transplantation HBV prophylaxis may result in a percentage of patients with persistent HBV DNA in the graft, the presence of HBV DNA in the liver graft may not be related to clinical HBV recurrence.

Low risk of hepatitis B reactivation in patients with severe COVID-19 who receive immunosuppressive therapy.

A significant proportion of patients infected with SARS‐CoV‐2 develop severe respiratory symptoms due to an excessive immune response. Treatment of this condition may include immunosuppressive therapies, such as IL‐6 receptor antagonists and corticosteroids, which pose a risk for patients with active or past hepatitis B virus (HBV) infection. In this prospective cohort study, we analysed the risk of HBV reactivation in patients with severe COVID‐19 and resolved HBV infection undergoing immunosuppressive therapy. From 15th March to 30th April 2020, 600 patients with severe COVID‐19 were admitted to our hospital and treated with immune modulators. Data regarding HBV infection were available in 484, of whom 69 (14%) were HBsAg negative/anti‐HBc positive. For these patients, HBV reactivation prophylaxis with entecavir was strongly recommended. Complete follow‐up was available in 61 patients: 72% were male, median age was 67 years, and anti‐HBs was >10 IU/mL in 72%. The immunosuppressive drug most used was tocilizumab (72%). Despite HBV prophylaxis recommendation, 38 (62%) patients received entecavir and 23 (38%) did not. Baseline features of both groups were similar. At follow‐up, we found no cases of HBsAg seroreversion and only 2 (3%) patients (no prophylaxis group) had detectable serum HBV‐DNA (<15 IU/mL). Both were anti‐HBs negative and had normal aminotransferase levels. Our data show that the risk of HBV reactivation in patients with severe COVID‐19 and resolved HBV infection undergoing immunosuppressive treatment is low. However, if a systematic follow‐up after hospital discharge is unfeasible in patients without anti‐HBs, a short course of antiviral prophylaxis may be a safe option.

P1674KIDNEY TRANSPLANTATION FROM HBSAG+ LIVING DONORS TO HBSAG- RECIPIENTS: CLINICAL OUTCOMES AT A HIGH-VOLUME CENTER

Abstract Background and Aims Data on kidney transplantation (KTx) from hepatitis B surface antigen (HBsAg)+ donors to HBsAg- recipients [D(HBsAg+)/R(HBsAg-)] are limited. We aimed to report the outcomes of D(HBsAg+)/R(HBsAg-) KTx in recipients with or without hepatitis B surface antibody (HBsAb). Method Eighty-three D(HBsAg+)/R(HBsAg-) living KTx cases were retrospectively identified. The 384 cases of KTx from hepatitis B core antibody (HBcAb)+ living donors to HBcAb- recipients [D(HBcAb+)/R(HBcAb-)] were used as the control group. Primary endpoint was post-transplant HBsAg -→+. Results Before KTx, 24 donors (28.9%) in the D(HBsAg+)/R(HBsAg-) group were hepatitis B virus (HBV) DNA+, and 20 recipients were HBsAb-. All eighty-three D(HBsAg+)/R(HBsAg-) recipients received HBV prophylaxis, while no D(HBcAb+)/R(HBcAb-) recipients received prophylaxis. After a median follow-up of 36 months (range 6-106) and 36 months (range 4-107) for the D(HBsAg+)/R(HBsAg-) and D(HBcAb+)/R(HBcAb-) groups, respectively, 2/83 (2.41%) D(HBsAg+)/R(HBsAg-) recipients and 1/384 (0.26%) D(HBcAb+)/R(HBcAb-) became HBsAg+, accompanied with HBV DNA+ (P=0.083). The three recipients with HBsAg-→+ were exclusively HBsAb-/HBcAb- before KTx. Recipient deaths were more frequent in the D(HBsAg+)/R(HBsAg-) group (6.02% vs. 1.04%, P=0.011), while liver and graft function, rejection, infection, and graft loss were not significantly different. In univariate analyses, pre-transplant HBsAb-/HBcAb- combination in the D(HBsAg+)/R(HBsAg-) recipients carried a significantly higher risk of HBsAg-→+, HBV DNA-→+, and death. Conclusion Living D(HBsAg+)/R(HBsAg-) KTx in HBsAb+ recipients provides excellent graft and patient survivals without HBV transmission. HBV transmission risks should be more balanced with respect to benefits of D(HBsAg+)/R(HBsAg-) KTx in HBsAb-/HBcAb- candidates.

Hepatitis B virus recurrence after liver transplantation: An old tale or a clear and present danger?

Hepatitis B virus (HBV) recurrence after liver transplantation (LT) has been described more than 50 years ago. Similarly, to other clinical conditions, in which impairment of host immune defense favors viral replication, early reports described in details recurrence and reactivation of HBV in liver transplant recipients. The evidence of a possible, severe, clinical evolution of HBV reappearance in a significant percentage of these patients, allowed to consider, for some years, HBV positivity a contraindication for LT. Moving from the old to the new millennium this picture has changed dramatically. Several studies contributed to establish efficient prophylactic protocols for HBV recurrence and with the advent of more potent anti-viral drugs an increased control of infection was achieved in transplanted patients as well as in the general immune-competent HBV population. Success obtained in the last decade led some authors to the conclusion that HBV is now to consider just as a “mere nuisance”. However, with regard to HBV and LT, outstanding issues are still on the table: (1) A standard HBV prophylaxis protocol after transplant has not yet been clearly defined; (2) The evidence of HBV resistant strains to the most potent antiviral agents is claiming for a new generation of drugs; and (3) The possibility of prophylaxis withdrawal in some patients has been demonstrated, but reliable methods for their selection are still lacking. The evolution of LT for HBV is examined in detail in this review together with the description of the strategies adopted to prevent HBV recurrence and their pros and cons.

Hepatitis B Reactivation in Liver Transplant Recipients With Hepatitis B Virus Core Antibody Positive Grafts: a Retrospective Study

Liver grafts from hepatitis B core antibody (anti-HBc) positive donors increasethe risk of hepatitis B virus (HBV) reactivation in recipients due to posttransplant immunosuppressive therapy. to study the HBV reactivation in liver transplant recipients with anti-HBc-positive donors. This was a retrospective study. Liver transplant recipients who received grafts from anti-HBc-positive donors between January 2013 and December 2017 were included in analysis. Hospital records of all subjects for a 2-year posttransplantation period were studied to observe reactivation of hepatitis B. As per our institute protocol, prophylaxis for HBV was given to subjects with either positive hepatitis B surface antigens or hepatitis B surface antibody (anti-HBs) titre <100 mIU/ml, after transplantation with anti-HBc-positive donor grafts. Recipients with anti-HBs titre >100 mIU/mL were exempted from prophylaxis and kept on regular monitoring for HBV markers. Of 85 liver transplant recipients, 20 subjects who received anti-HBc-positive grafts were included in analysis. The mean age of the study population was 46 years (range 2-68 years). The most common aetiology of cirrhosis in our study population was cryptogenic followed by ethanol. Among the study population, 16 (80%) transplant recipients had anti-HBs titre less than 100 mu/ml and 4 (20%) subjects had anti-HBs>100 miu/ml. HBV reactivation occurred in 6 (30%) subjects. Reactivation was seen even in those who received HBV prophylaxis, while none of the subjects with anti-HBs titre >100 miu/ml developed HBV reactivation despite absence of prophylaxis. HBV reactivation can occur even in the presence of target anti-HBs titre (i.e. >10 miu/ml) and HBV prophylaxis during postliver transplantation. However, HBV reactivation is not seen in recipients with anti-HBs titre of >100 miu/ml.

Hepatitis B prophylaxis in adolescents who present for examination after alleged sexual assault.

In Australia, the risk of hepatitis B virus (HBV) transmission from single sexual contact is low. This, combined with assumed widespread immunity from vaccination, has resulted in a lack of clarity surrounding the necessity for hepatitis B post-exposure prophylaxis following recent sexual assault. This retrospective audit was conducted through the Victorian Forensic Paediatric Medical Service (VFPMS) at the Royal Children's Hospital, Melbourne, Australia. Subjects were patients aged 13-17 years who presented to VFPMS between 1 January 2007 and 31 December 2016 for forensic medical examination following an alleged penetrative sexual assault. Data collected included subject demographics, immunisation status, route of potential HBV exposure, time between alleged sexual assault and presentation, whether HBsAb levels were tested and the results and whether HBV prophylaxis was administered to the subject and its timing. A total of 2121 records were reviewed, and 420 subjects were found to be eligible for inclusion; 26.2% (n = 110) had HBsAb levels measured at initial presentation. Of these 110 subjects, 45.5% (n = 50) had titre levels less than 10 (deemed to be non-protective) and were therefore vulnerable to HBV infection. Of the 420 subjects, 4.5% (n = 19) received HBV prophylaxis as a result of their assessment. Results suggest that a high proportion of Australian adolescents presenting following recent sexual assault may be at risk of hepatitis B infection. Very few received timely prophylaxis. Follow-up attendance rates were poor. Administration of the hepatitis B booster vaccine at the point of contact may reduce the risk of HBV infection in this group of adolescents.

Hepatitis B seroprevalence in hematological oncology patients

Objectives: Hepatitis B virus (HBV) infection is still a serious public health problem today. Many factors such as frequent blood transfusion, hemodialysis, sexual contact, sterilization in surgical procedures, etc. are involved in the transmission of hepatitis B virus. In our study, HBV seroprevalence was evaluated retrospectively in order to provide vaccination of anti-HBs negative patients and to determine HBV prophylaxis in patients with hematological malignancy. Methods: A total of 499 patients were included in the study. HBsAg, anti-HBs, anti-HBc IgG, anti-HDV, HBV DNA values were measured by ELISA (enzyme-linked immunosorbent assay, Liason, Diasorin, Italy) with Real-Time PCR (Cobas-Tagman, Roche Switzerland) and recorded. The obtained datas were evaluated by SPSS for Windows 15.00 statistical program. A value of p &amp;lt;0.05 was accepted as a statistical significance value. Results: HBsAg positivity was found to be 3.4% (n = 17) in all patients. Appropriate treatment regimens were started to patients with HBsAg (+). There were 166 (33.3%) patients with anti-HBs (+). One hundred nineteen (23.8%) patients had anti-HBc IgG (+), 40 (33.6%) of them were started a prophylactic treatment regimen. Anti-HBs positivity were reported after vaccination in 48 (16.8%) patients. Occult hepatitis have not been detected in patients with anti-HBc IgG positivity. Conclusions: As a result of this study, anti-HBs negative patients with hematological malignancies were vaccinated. Patients and physicians should be informed about vaccination and hepatitis serology controls of hematological malignancy and other immunosuppressed patients. Sensitivity in this context should be increased in terms of prophylactic treatments.

Kidney Transplantation From Hepatitis B Surface Antigen (HBsAg)-Positive Living Donors to HBsAg-Negative Recipients: Clinical Outcomes at a High-Volume Center in China.

Data on kidney transplantation (KTx) from hepatitis B surface antigen (HBsAg)-positive (HBsAg+) donors to HBsAg-negative (HBsAg-) recipients [D(HBsAg+)/R(HBsAg-)] are limited. We aimed to report the outcomes of D(HBsAg+)/R(HBsAg-) KTx in recipients with or without hepatitis B surface antibody (HBsAb). Eighty-three D(HBsAg+)/R(HBsAg-) living KTx cases were retrospectively identified. The 384 cases of KTx from hepatitis B core antibody-positive (HBcAb+) living donors to HBcAb-negative (HBcAb-) recipients [D(HBcAb+)/R(HBcAb-)] were used as the control group. The primary endpoint was posttransplant HBsAg status change from negative to postive (-- →+). Before KTx, 24 donors (28.9%) in the D(HBsAg+)/R(HBsAg-) group were hepatitis B virus (HBV) DNA positive, and 20 recipients were HBsAb-. All 83 D(HBsAg+)/R(HBsAg-) recipients received HBV prophylaxis, while no D(HBcAb+)/R(HBcAb-) recipients received prophylaxis. After a median follow-up of 36 months (range, 6-106) and 36 months (range, 4-107) for the D(HBsAg+)/R(HBsAg-) and D(HBcAb+)/R(HBcAb-) groups, respectively, 2 of 83 (2.41%) D(HBsAg+)/R(HBsAg-) recipients and 1 of 384 (0.26%) D(HBcAb+)/R(HBcAb-) became HBsAg+, accompanied by HBV DNA-positive (P = .083). The 3 recipients with HBsAg-→+ were exclusively HBsAb-/HBcAb- before KTx. Recipient deaths were more frequent in the D(HBsAg+)/R(HBsAg-) group (6.02% vs 1.04%, P = .011), while liver and graft function, rejection, infection, and graft loss were not significantly different. In univariate analyses, pretransplant HBsAb-/HBcAb- combination in the D(HBsAg+)/R(HBsAg-) recipients carried a significantly higher risk of HBsAg-→+, HBV DNA-→+, and death. Living D(HBsAg+)/R(HBsAg-) KTx in HBsAb+ recipients provides excellent graft and patient survivals without HBV transmission. HBV transmission risks should be more balanced with respect to benefits of D(HBsAg+)/R(HBsAg-) KTx in HBsAb-/HBcAb- candidates.

Hepatitis B virus among hematopoietic stem cell transplant recipients: Antiviral impact in seroconversion, engraftment, and mortality in a Latin American center.

Hepatitis B virus (HBV) infection is a worldwide concern with a broad distribution. In immunosuppressed populations, such as solid organ and hematopoietic stem cell transplant (HSCT) recipients, it can reactivate leading to acute hepatic failure. Different risk factors are known for higher rates of reactivation, and entecavir, tenofovir, and lamivudine are often used for prophylaxis and treatment. However, data regarding the impact of antiviral drugs in neutrophil and platelet engraftment are still unknown and concern the management of viral hepatitis post-HSCT. We performed a single-center, retrospective, observational study reviewing medical records of patients referred for hematopoietic stem cell transplant from 2010 to 2017, which were also HBV infected, aiming to describe outcomes related to antiviral treatment and also the impact on platelet and neutrophil recovery after transplant. A secondary goal consisted of analyzing the impact of HBV infection in early and late mortality post-HSCT. The study included patients with positive blood bank screening for hepatitis B infection (HBsAg, Anti-HBc or HBV-NAT), confirmed later on by a laboratory routine serology. A total of 1132 hematopoietic stem cell recipients were assessed between 2010 and 2017. Eighty-six patients were confirmed to have HBV infection, of which six were HBsAg-positive, 20 were isolated anti-HBc-positive, and 60 had resolved infection (anti-HBc-positive and anti-HBs-positive). With regard to prophylaxis, 19 patients underwent HSCT on HBV antiviral therapy or prophylaxis: two were HBeAg-positive, three were HBeAg-negative and HBV-DNA was only detectable in three of them. Moreover, one patient had an occult HBV infection. Regarding therapy, 9 patients were on entecavir, 6 patients on lamivudine, two on tenofovir, and two of them on a combination of tenofovir+lamivudine due to HIV co-infection. Reverse seroconversion was not identified in any patients receiving antiviral therapy or prophylaxis, but it was detected in one patient with occult hepatitis B and another with resolved infection. No severe side effects led to therapy discontinuation in the treated group, which also did not have any significant delay in neutrophil or platelet engraftment when compared to patients without antiviral therapy. In addition, the only factors associated with increased mortality were transplant onset after 50years, allogeneic transplant and myeloablative conditioning regimens. Interestingly, the presence of HBsAg or detectable HBV-DNA was not related to worse outcomes, neither the use of rituximab. In multivariate analysis, the use of antiviral therapy, the occurrence of graft-versus-host disease or CMV reactivation also was not linked to increased mortality. To sum up, HBV serology, ALT, and HBV-DNA monitoring are essential to detect hepatic flares earlier, even in populations with chronic inactive hepatitis, due to the possibility of later seroconversion. HBV infection was not related to increased 2-year mortality post-transplant. Antiviral prophylaxis did not cause any important clinical or laboratory side effects that could demand discontinuation, and its use was not associated with later neutrophil and platelet engraftments.