Hepatitis B Virus DNA Monitoring Research Articles

Impact of Mogamulizumab-Containing Chemotherapy on HBV Reactivation in Patients with T-Cell Lymphoma: A Multicenter Retrospective Observational Study (PROACTIVE-MOGA)

INTRODUCTION Reactivation of hepatitis B virus (HBV) infection is a potentially lethal complication, but may be preventable in patients with chronic HBV infection or resolved HBV infection who receive systemic chemotherapy.The risk of HBV reactivation (HBVR) depends on not only HBV infectious status but also type of systemic chemotherapy. An anti-CCR4 antibody, mogamulizumab (Moga), has been developed for the treatment of peripheral T-cell lymphomas. Moga is known to suppress CCR4-positive regulatory T cells and helper T cells, which can lead to immunological dysfunction. However, there is little evidence regarding the risk of HBVR in patients with chronic HBV infection or resolved HBV infection who receive Moga-containing systemic chemotherapy. We conducted a retrospective observational study to evaluate the risk of HBVR and clinical outcome in those patients. METHODS & MATERIALS: Patients treated with Moga-containing chemotherapy for T-cell lymphoma between May 2012 and March 2021, who were chronic HBV infection (defined as seropositive for HBsAg) or resolved HBV infection (defined as seronegative for HBsAg, but seropositive for anti-HBc or anti-HBs), were included. The primary endpoint was the rate of HBVR; HBVR in HBsAg-positive patients was defined as any of the following three criteria: 1) 2 log or more increase in HBV DNA from baseline, 2) 3.0 Log IU/ml or more of HBV DNA in patients with undetectable HBV DNA at baseline, 3) 4.0 Log IU/ml or more of HBV DNA in patients not available for HBV DNA at baseline. HBVR in HBsAg-negative patients was defined as any of following three criteria: 1) detectable for HBV DNA in patients with undetectable HBV DNA at baseline, 2) 1.3 Log IU/mL or more of HBV DNA in patients not available for HBV DNA at baseline, 3) seroconversion of HBsAg. RESULTS: A total of 23 HBsAg-positive patients and 246 resolved HBV-infected patients were retrospectively reviewed. Among the 23 HBsAg-positive patients, the median age was 65 years (interquartile range [IQR], 63-73) and 19 patients (82%) had adult T-cell leukemia-lymphoma (ATL). Baseline HBV DNA was undetectable level, detectable not quantifiable, and detectable in 9 (39%), 2 (9%), and 12 (52%) patients, respectively. All 23 HBsAg-positive patients received anti-HBV prophylaxis prior to Moga treatment. One of 23 (4.3%) patients experienced HBVR who led to HBV-related hepatitis. Among the 241 patients with resolved HBV infection, the median age was 65 years (IQR, 63-73) and 223 patients (91%) had ATL. Baseline serostatus of anti-HBc and anti-HBs were as follows: anti-HBc positive and anti-HBs positive in 177 patients (72%), anti-HBc-positive but anti-HBs negative in 50 (20%), the remaining 9 were anti-HBc negative but anti-HBs positive. Baseline HBV DNA was undetectable in 233 (95%), detectable not quantifiable in 5 (2%), and the remaining 3 were detectable for HBV DNA. Only 3 patients received anti-HBV prophylaxis. HBVR occurred in 11 patients, and the 2-year cumulative HBVR rate was 3.5% (95% CI, 1.6-16.5). Among the 11 patients with HBVR, the median peak HBV DNA level was 2.1 Log IU/mL (IQR, 1.7-5.0), the median time from first dose of Moga to HBVR was 140 days (IQR, 82-765) and 2 had HBV-related hepatitis. CONCLUSION: Our current study showed that the risk of HBVR was 4.3% (1 of 23) among HBsAg-positive patients with antiviral prophylaxis and 4.6% (11 of 238) among resolved HBV-infected patients without antiviral prophylaxis following Moga-containing chemotherapy. Anti-HBV prophylaxis and HBV DNA monitoring guided preemptive anti-HBV therapy are recommended to prevent HBV-related hepatitis for HBsAg-positive and resolve HBV-infected patients, respectively.

Hepatitis B infection or reactivation after switch to two-drug antiretroviral therapy: A case series, literature review, and management discussion.

Two-drug antiretroviral therapy (ART) without hepatitis B virus (HBV) activity is prescribed for persons with HIV as simplified or salvage therapy. While two-drug regimens are not recommended for persons with chronic HBV infection, guidelines do not address use in those with HBV susceptibility and/or core antibody reactivity. We present a case series of individuals with HBV infection or reactivation following switch to two-drug, non-HBV-active ART. HIV primary care clinics of an academic medical center in New York, NY. Case surveillance was conducted to identify persons with HBV surface antigenemia and viremia following two-drug ART switch. Clinical characteristics and outcomes were ascertained through chart review. Four individuals with HBV infection or reactivation after ART switch were identified. Two had HBV susceptibility, one had core antibody reactivity, and one had surface antigen reactivity pre-switch. All eligible persons had received HBV vaccination, two with low-level antibody response and one with persistent nonresponse. Two presented with fulminant hepatitis, one requiring liver transplantation. Two-drug ART switch may pose risk of HBV infection or reactivation. We propose careful patient selection and monitoring through the following: 1) Assessment of HBV serologies before switch and periodically thereafter, 2) Vaccination and confirmation of immunity before switch, 3) Risk stratification and counseling about HBV reactivation for those with core antibody, 4) Preemptive HBV DNA monitoring for those at risk of reactivation, 5) Continuation of HBV-active prophylaxis when above measures are not feasible, 6) Continuation of HBV-active therapy and surveillance for chronic HBV infection.

Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies in the targeted therapy era.

Hepatitis due to hepatitis B virus (HBV) reactivation can be serious and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. Patients with inactive and even resolved HBV infection still have persistence of HBV genomes in the liver. The expression of these silent genomes is controlled by the immune system. Suppression or ablation of immune cells, most importantly B cells, may lead to reactivation of seemingly resolved HBV infection. Thus, all patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen. Patients found to be positive for HBsAg should be given prophylactic antiviral therapy. For patients with resolved HBV infection, there are two approaches. The first is pre-emptive therapy guided by serial HBV DNA monitoring, and treatment with antiviral therapy as soon as HBV DNA becomes detectable. The second approach is prophylactic antiviral therapy, particularly for patients receiving high-risk therapy, especially anti-CD20 monoclonal antibody or hematopoietic stem cell transplantation. Entecavir and tenofovir are the preferred antiviral choices. Many new effective therapies for hematological malignancies have been introduced in the past decade, for example, chimeric antigen receptor (CAR)-T cell therapy, novel monoclonal antibodies, bispecific antibody drug conjugates, and small molecule inhibitors, which may be associated with HBV reactivation. Although there is limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBsAg-positive patients receiving novel treatments, including Bruton's tyrosine kinase inhibitors, B-cell lymphoma 2 inhibitors, and CAR-T cell therapy. Further studies are needed to determine the risk of HBV reactivation with these agents and the best prophylactic strategy.

Management of Hepatitis B Virus Reactivation after the Completion of Cancer Chemotherapy using a Plan-do-Check-Act Cycle

The reactivation of the hepatitis B virus (HBV) following systemic chemotherapy reportedly caused acute liver dysfunction as a fatal complication. HBV reactivation sometimes occurs even after the cessation of chemotherapy, especially in the patients with hematological malignancies. A retrospective survey of patients with hepatitis B surface (HBs) antigen-negative cancer with HBs and/or HBc antibodies was conducted by a multidisciplinary chemotherapy team to determine the examination rate of the HBV DNA test after the completion of chemotherapy. Among 83 patients with a resolved HBV infection, who were followed up for more than 3 months, only 17 patients underwent HBV DNA monitoring every 1-3 months (17/83; 20.5%). Since September, 2022, the chemotherapy team has informed the attending physician regarding the continuous HBV DNA monitoring in patients with cancer with a resolved HBV infection until 12 months after the cessation of chemotherapy.

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.

Managing the Risk of Hepatitis B Virus Reactivation in Patients with B-Cell Lymphomas Treated with Obinutuzumab or Rituximab Immunochemotherapy

Introduction: Reactivation of hepatitis B virus (HBV) is an identified risk associated with immunochemotherapy for non-Hodgkin lymphoma (NHL) in patients (pts) with resolved HBV infection. This study aimed to evaluate the risk of HBV reactivation and explore risk factors in NHL pts with resolved HBV infection who received anti-CD20 antibody (obinutuzumab or rituximab)-containing immunochemotherapy in the phase III GOYA and GALLIUM studies (involving pts with previously untreated diffuse large B-cell lymphoma [DLBCL] and indolent NHL, respectively). Methods: Pts were randomized to receive induction with either obinutuzumab (1000 mg on days 1, 8, and 15 of cycle 1, and day 1 of cycles 2‒8) or rituximab (375 mg/m2 on day 1 of each cycle) in combination with CHOP (GOYA and GALLIUM), CVP (GALLIUM), or bendamustine (GALLIUM) for 6-8 cycles. In GALLIUM, induction was followed by obinutuzumab or rituximab maintenance. Baseline screening was performed locally for hepatitis B surface antigen (HBsAg) and antibody against hepatitis B core antigen (anti-HBc). Pts positive for HBsAg were excluded, while those with resolved HBV infection (HBsAg-negative but anti-HBc-positive) could be enrolled if they had baseline HBV DNA Results: Of 2797 evaluable pts (GOYA, 1407; GALLIUM, 1390), 326 pts were seropositive for anti-HBc (207 were seropositive for antibodies against HBsAg) and 11 had detectable but non-quantifiable HBV DNA (10 to Conclusions: HBV DNA monitoring-guided preemptive NAT was effective in preventing HBV-related hepatitis during treatment with obinutuzumab- or rituximab-containing immunochemotherapy. Antiviral prophylaxis was effective in preventing HBV reactivation and may be an appropriate option for pts with resolved HBV infection and multiple risk factors. Disclosures Kusumoto: Chugai: Honoraria, Other: GALLIUM and GOYA are sponsored by F. Hoffmann-La Roche Ltd. Third-party medical writing support, under the direction of Shigeru Kusumoto, was provided by Cheryl Wright of Gardiner-Caldwell Communications, and was funded by F. Hoffmann-La Roche Ltd, Research Funding. Arcaini: Celgene, Roche, Sandoz: Consultancy; Gilead: Research Funding; Pfizer, Celgene, Bayer, Roche: Membership on an entity9s Board of Directors or advisory committees. Kim: JJ Takeda: Research Funding; Celltrion, Inc: Consultancy, Honoraria; Novartis: Research Funding; Roche: Research Funding; Donga: Research Funding; Mundipharma: Research Funding; Kyowa-Kirin: Research Funding. Peters: Genentech, Merck: Honoraria; Roche: Honoraria. Tanaka: BMS: Honoraria, Research Funding; Chugai: Honoraria, Research Funding; GSK: Honoraria, Research Funding. Zelenetz: Celgene: Consultancy; Amgen: Consultancy. Kuriki: Chugai: Employment. Fingerle-Rowson: F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Nielsen: F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Ueda: Chugai: Employment. Piper-Lepoutre: Roche: Employment. Sellam: Roche: Employment. Tobinai: Daiichi Sankyo Co., Ltd: Consultancy, Honoraria; AbbVie: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; HUYA Bioscience: Honoraria; Chugai: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; GlaxoSmithKline: Research Funding; Janssen: Honoraria, Research Funding; Kyowa Hakko Kirin: Honoraria, Research Funding; Mundipharma: Honoraria, Research Funding; Ono Pharmaceutical: Honoraria, Research Funding; Servier: Research Funding; Takeda: Honoraria, Research Funding; Zenyaku Kogyo: Honoraria.

Effects of Antiviral Therapy on HBV Reactivation and Survival in Hepatocellular Carcinoma Patients Undergoing Hepatic Artery Infusion Chemotherapy.

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<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).ConclusionsHBV 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 RegisterHAIC Using Oxaliplatin Plus Fluorouracil/Leucovorin for Patients with Locally Advanced HCC.Clinical Trial Registration https://www.clinicaltrials.gov/, identifier NCT 02436044

Impact of long-term systemic treatment for psoriasis on liver disease in psoriasis patients with coexisting hepatitis B virus infection.

Continuously updated information is helpful for evaluating the safety of long-term systemic drug use in psoriasis patients with concomitant hepatitis B virus (HBV) infection. To investigate the impact of long-term systemic treatment for psoriasis on liver disease in psoriasis patients with HBV infection. Data of patients during 10-year period were recorded and analyzed. Sixty-six patients (46 males and 20 females) with a mean age of 58.5 ± 13.1 years were recruited. Our study estimated that the 5-year cumulative risks of developing cirrhosis and HCC were 30% and 5%, respectively, in patients receiving systemic treatments for psoriasis. Risks of cirrhosis and HCC were not significantly different between systemic and topical treatment groups. Thirty patients were prescribed systemic treatments (acitretin, methotrexate, ciclosporin, and anti-tumor necrosis factors). Three HBsAg+ patients developed viral reactivation (two patients with methotrexate and one patient with ciclosporin). The effects of systemic treatments for psoriasis on liver outcome in patients with coexisting HBV infection are needed to be determined. HBsAg+ patients are more likely to develop viral reactivation during systemic treatment for psoriasis than HBsAg- patients. Monitoring of liver enzymes and HBV DNA every 3 months is recommended during treatment and for 6 to 12 months after drug discontinuation.

Cost-effectiveness analysis for preventing hepatitis B virus reactivation-related death in Japan

Abstract Background There is no worldwide standard recommendation for preventing hepatitis B virus (HBV) reactivation for patients with resolved infection treated with an anti-CD20 antibody for B-cell non-Hodgkin lymphoma. This study aims to compare the cost-effectiveness between two commonly used strategies to prevent HBV reactivation-related death. Methods The two strategies compared were prophylactic antiviral therapy (Pro NAT) and HBV DNA monitoring followed by on-demand antiviral therapy (HBV DNA monitoring) using entecavir (Entecavir, a generic drug for Baraclude). Effectiveness was defined as the prevention of death due to HBV reactivation and costs were calculated under the health insurance system of Japan as of April 2018 using Markov model. A cost-minimization analysis, one of the cost-effectiveness analyses, was applied, since the effectiveness was the same between the two strategies according to a meta-analysis. To consider the effect of uncertainty for each parameter, probabilistic sensitivity analysis (PSA) was performed. In the scenario analysis, costs were calculated using lamivudine (Zefix) or tenofovir alafenamide (Vemlidy) instead of entecavir. All analyses were done using TreeAge Pro 2019 (TreeAge Software, Inc., MA, USA). Results Estimated costs per patient during the 30 months after initiation of chemotherapy for lymphoma were 1,513 USD with Pro NAT and 1,265 USD with HBV DNA monitoring. A PSA revealed that HBV DNA monitoring was more consistently cost-effective compared with Pro NAT when some parameters were set randomly according to probability distributions. In our scenario analysis, costs of Pro NAT and HBV DNA monitoring were calculated as 2,762 and 1,401 USD using lamivudine, 4,857 and 1,629 USD using tenofovir alafenamide. Conclusions Our cost-effectiveness analysis shows that an HBV DNA monitoring strategy using entecavir should be recommended for preventing HBV reactivation-related death in Japan. Key messages Cost-effectiveness analysis demonstrated that HBV DNA monitoring was more cost-effective compared to Pro NAT; this result was consistent with PSA. HBV DNA monitoring strategy should be recommended to prevent HBV reactivation-related death for the patients with resolved HBV infection in Japan.

Evaluation of hepatitis B virus in clinical trials of baricitinib in rheumatoid arthritis

BackgroundReactivation of hepatitis B virus (HBV) replication is a well-recognised complication in patients receiving disease-modifying anti-rheumatic drugs (DMARDs) for rheumatoid arthritis (RA). Limited data exist on HBV reactivation among patients...

Isolated Anti-HBc: Significance and Management.

Hepatitis B virus (HBV) infection is prevalent worldwide and is associated with dramatic levels of morbidity and mortality. Isolated anti-HBc (IAHBc) is a particular serological pattern that is commonly found in immunocompromised patients. There is ongoing debate regarding the management of patients with IAHBc. Herein, we summarize the current guidelines and the newest evidence. The frequency of IAHBc is variable, with a higher prevalence in some populations, such as persons living with HIV and others immunocompromised patients. The risk of HBV reactivation depends on host factors (including immunosuppression) and viral factors. It is now well established that immunocompromised patients can be classified into three groups for risk according to the type of immunosuppression and/or treatment. In patients at high risk, HBV therapy has to be considered systematically. In patients at moderate risk, the decision is based on the level of HBV DNA (preemptive treatment or monitoring and vaccination). In patients with low risk, HBV vaccination is another possible approach, although further studies are needed to assess the type of preemptive strategy.

2401 A Case of Hepatitis B Reactivation

INTRODUCTION: It is estimated that more than two billion people around the world have been infected by hepatitis B virus (HBV). Several immunosuppressive agents have been associated with HBV reactivation (HBVr). We present a case of HBVr in a patient with ulcerative colitis (UC) treated with tofacitinib. CASE DESCRIPTION/METHODS: A 57-year-old female with UC on tofacitinib presented to the emergency department with flu-like symptoms for 2 months after being switched from azathioprine to tofacitinib. She was HBV surface antigen (HBsAg) negative, anti-HBV core antibody (anti-HBcAb) and anti-HBV surface antibody (anti-HBsAb) positive and had normal liver enzymes before initiation of tofacitinib. On initial evaluation she was febrile, hypotensive, and had lower extremity edema. Laboratory data was significant for total bilirubin 2.5 mg/dL, AST 1601 U/L, ALT 1013 U/L, positive HBsAg, anti-HBsAb, total anti-HBcAb and HBeAg, HBV DNA 10,354,246 IU/m; she had negative HBeAb, IgM antibody to HBcAg, hepatitis A, C and E antibodies. She was diagnosed with HBVr and was started on tenofovir disoproxil fumarate. Over the next two days her enzymes continued to rise and peaked at day 5. At day 7 liver enzymes started to trend down. She was later discharged on tenofovir. At the 2 month follow up liver enzymes had normalized and HBV DNA was down to 30 IU/m. DISCUSSION: Tofacitinib is a kinase inhibitor extensively studied in patients with rheumatoid arthritis and has been shown to be generally safe in multiple clinical trials. In patients with UC the data is limited. Most clinical trials excluded patients with chronic HBV infection, therefore the risk of HBVr among tofacitinib-treated patients remains unknown. HBVr is defined as an increase in HBV DNA of more than 100-fold in patients with previously detected HBV DNA, detection of HBV DNA in patients that previously had undetectable titers or when reverse seroconversion or development of detectable HBsAg occurs. In this case, the reactivation of HBV was most likely induced by tofacitinib and its suppression of various kinase signaling pathways essential for controlling immune activation and proliferation the cells responsible of preventing HBV replication. In conclusion, in patients with resolved HBV infection who are HBsAg negative and anti-HBcAb positive, periodic HBV DNA monitoring should be considered as HBVr is possible and the exact risk of reactivation remains unknown.

Cost-effectiveness of preventing hepatitis B virus reactivation in patients with lymphoma and resolved HBV infection

Hepatitis B virus (HBV) reactivation may occur in >10% of patients with lymphoma and resolved HBV infection who undergo rituximab-containing chemotherapy. Preventive strategies may have marked impact on resource allocation in HBV endemic areas. This study aims to compare the cost-effectiveness between prophylactic antiviral therapy and HBV DNA monitoring for the prevention of HBV-related complications. Data sources are studies of HBV-related events and survival for patients with lymphoma and resolved HBV infection published since 2006. Decision tree analysis was used to compare the incremental cost-effectiveness ratio (ICER) of preventing HBV-related death or liver decompensation for patients who undergo first-line rituximab-containing chemotherapy. Sensitivity analysis was performed to examine the impact of the preventive efficacy, the duration of prophylactic antiviral therapy, and the cost of different interventions. The direct medical cost was derived from the database of the NHI Administration, Taiwan. The time frame of our analysis was set to 3 years after the completion of chemotherapy. The median ICER of prophylactic antiviral therapy, according to current practice guidelines, ranged between USD 150,000 and 250,000 if we apply the guidelines generally. When a long-course (12 months after completion of chemotherapy according to clinical guidelines) prophylactic therapy was assumed, Option A was cheaper and more effective only in the anti-HBs-negative subgroup (median ICER US$149,932 vs. US$161,526, p=0.013). Identification of anti-HBs-negative subgroups is critical to improve the cost-effectiveness of prophylactic antiviral therapy in lymphoma patients with resolved HBV infection.

Clinical outcomes of hepatitis B or C virus infections in patients with malignant lymphoma receiving autologous stem cell transplantation: on behalf of the Adult Lymphoma Working Group of the Japan Society for Haematopoietic Cell Transplantation (JSHCT)

Clinical outcomes of hepatitis B or C virus infections in patients with malignant lymphoma receiving autologous stem cell transplantation: on behalf of the Adult Lymphoma Working Group of the Japan Society for Haematopoietic Cell Transplantation (JSHCT)

Risk of HBV reactivation in patients with B-cell lymphomas receiving obinutuzumab or rituximab immunochemotherapy

AbstractRisk of hepatitis B virus (HBV) reactivation was assessed in B-cell non-Hodgkin lymphoma (NHL) patients with resolved HBV infection (hepatitis B surface antigen negative, hepatitis B core antibody positive) who received obinutuzumab- or rituximab-containing immunochemotherapy in the phase 3 GOYA and GALLIUM studies. HBV DNA monitoring was undertaken monthly to 1 year after the last dose of study drug. In case of HBV reactivation (confirmed, HBV DNA ≥29 IU/mL), immunochemotherapy was withheld and nucleos(t)ide analog treatment (preemptive NAT) started. Immunochemotherapy was restarted if HBV DNA became undetectable or reactivation was not confirmed, and discontinued if HBV DNA exceeded 100 IU/mL on NAT. Prophylactic NAT was allowed by investigator discretion. Among 326 patients with resolved HBV infection, 27 (8.2%) had HBV reactivation, occurring a median of 125 days (interquartile range, 85-331 days) after the first dose. In 232 patients without prophylactic NAT, 25 (10.8%) had HBV reactivation; all received preemptive NAT. Ninety-four patients received prophylactic NAT; 2 (2.1%) had HBV reactivation. No patients developed HBV-related hepatitis. On multivariate Cox analysis, detectable HBV DNA at baseline was strongly associated with an increased risk of reactivation (adjusted hazard ratio [HR], 18.22; 95% confidence interval [CI], 6.04-54.93; P < .0001). Prophylactic NAT was strongly associated with a reduced risk (adjusted HR, 0.09; 95% CI, 0.02-0.41; P = .0018). HBV DNA monitoring–guided preemptive NAT was effective in preventing HBV-related hepatitis during anti–CD20-containing immunochemotherapy in B-cell NHL patients with resolved HBV infection. Antiviral prophylaxis was also effective and may be appropriate for high-risk patients. These trials were registered at www.clinicaltrials.gov as NCT01287741 (GOYA) and NCT01332968 (GALLIUM).

Hepatitis B Virus (HBV) Screening and Associated Outcomes in Malignant Hematology Patients Receiving Rituximab Therapy within the Rossy Cancer Network

Introduction. Hepatitis B Virus (HBV) reactivation is an important risk of Rituximab therapy, a potent immunosuppressant used as part of chemotherapy regimens against non-Hodgkin's lymphoma. HBV reactivation is a potentially fatal complication that can be largely prevented with antiviral prophylaxis and monitoring of HBV DNA. American Society of Clinical Oncology (ASCO) 2015 guidelines recommend that all patients be screened for both hepatitis B core antibody (anti-HBc) and surface antigen (HBsAg) before initiating Rituximab therapy. According to ASCO, the rates of screening for non-Hodgkin's lymphoma patients before the administration of Rituximab were less than 70% in 2014 for US centers participating in ASCO's Quality Oncology Practice Initiative. A 2014/15 study at the McGill University Health Centre found that about a third of patients were inadequately screened (A Lawandi, et al).Methods. The objective of this retrospective study was to assess the quality of HBV screening and monitoring at the partner hospitals of the Rossy Cancer Network (RCN). From the pharmacy database of the Jewish General Hospital, McGill University Health Centre, and St. Mary's Hospital Center, we obtained the set of patients with hematologic malignancies who began Rituximab treatment between April 2014 and March 2016. We then collected laboratory data on the screening of anti-HBc and HBsAg. Screening was considered appropriate if performed for both anti-HBc and HBsAg in the 6-month window preceding Rituximab administration and considered suboptimal if patients were tested outside this time frame, or for only one of the two tests. Additionally, patient chart reviews were used to collect follow-up information and outcomes for screened patients. Follow-up was considered appropriate when anti-viral treatment was given for infected patients and when patients at risk for reactivation received prophylactic treatment or HBV DNA monitoring.Results. Four hundred and seventy-four patients initiated Rituximab-containing treatment. Of those, 213 (45%) met the criteria for appropriate HBV screening and 138 (29%) for suboptimal screening. Of the patients that were screened (N=351), 6 were actively infected (HBsAg+/ anti-HBc+) and 41 were at risk for reactivation (HBsAg-/ anti-HBc+). All actively infected patients received antiviral treatment as per ASCO guidelines but only 18 (44%) of patients at risk for reactivation received appropriate follow-up, prophylactic treatment or HBV DNA monitoring. HBV reactivation was noted in 2 patients, one of whom died of a hepatic flare.Conclusion. Between 2014 and 2016, less than 50% of Rituximab-treated hematologic cancer patients within the RCN partnered hospitals were appropriately screened for HBV, and 44% of patients at risk for reactivation received appropriate follow-up. In response to these findings, the RCN Hematology Disease Site Group is developing RCN clinical practice guidelines to standardize HBV testing and management of patients at-risk for HBV reactivation. In close collaboration with virologists and hepatologists, the group will provide targeted education sessions to improve compliance with clinical practice guidelines. Additionally, the group aims to implement pharmacy-based interventions, such as coupling Rituximab prescriptions with standard orders for HBV testing, and providing pharmacist autonomy to order HBV testing. DisclosuresAssouline:Novartis: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria, Research Funding, Speakers Bureau; Roche: Honoraria, Research Funding, Speakers Bureau.

Monitoring and Treatment of Patients Undergoing Immunotherapy With Anti-CD20 Who are Exposed to HBV

Reactivation of hepatitis B virus (HBV) is a potentially fatal complication of immunosuppressive therapy, and can occur in individuals who are hepatitis B surface antigen (HBsAg) negative but positive for hepatitis B core antibody (anti-HBc). While anti-HBc positivity indicates prior HBV exposure, it may also reflect clearance of HBsAg, but with viral persistence at low intrahepatic replicative and transcriptional levels.1 HBV reactivation can still occur during intense immunosuppression, including B cell-depleting therapy with anti-CD20 antibodies2 and hematopoietic stem cell transplantation.3 While prevention via antiviral prophylaxis is recommended, it remains uncertain, from a global perspective, if this is an ideal and cost-effective strategy. An alternative is regular HBV DNA monitoring.4 However, this approach is problematic in resource-constrained regions, where the logistics of sample collection, transportation, and molecular analysis in dedicated facilities poses challenges.5 We aimed to evaluate the effectiveness of simple monitoring strategies using routine liver biochemistry and serum HBsAg in preventing HBV-related complications during anti-CD20 therapy.

Hepatitis B virus reactivation in patients with rheumatoid arthritis: Analysis of the National Database of Japan.

This study aimed to determine the incidence and risk factors for hepatitis B virus (HBV) reactivation in patients with rheumatoid arthritis (RA) undergoing immunosuppressive therapy. The National Database of Japan, in which insurance claim data have been comprehensively accumulated, was utilized. The subjects were 76641 RA patients who were plausibly initiated on immunosuppressive therapy from April 2013 to March 2014. Laboratory tests of the hepatitis B surface antigen, anti-hepatitis B virus surface antibody, and anti-hepatitis B virus core antibody were performed in 28.23%, 12.52% and 14.63% of patients, respectively, when the therapy was initiated. We found that HBV reactivation and fulminant hepatitis occurred in both the patients with and without HBV DNA monitoring, indicating insufficient monitoring in Japan during the study. The cumulative incidence of HBV reactivation over 24months was 1.57% (95% confidence interval [CI]=1.28%-1.92%) in the monitoring group, which consisted of those with resolved HBV infection. Glucocorticoid administration was a potent risk factor for HBV reactivation (hazard ratio [HR] =1.70, 95% CI=1.26-2.29, P=.001 in all subjects, and HR=1.82, 95% CI=1.18-2.81, P=.007 in the nonmonitoring group), although it was not statistically significant in the monitoring group (HR=1.49, 95% CI=0.99-2.26 and P=.057). No significant risk difference was observed between single administration of methotrexate and biological drugs.

Community-Based Services to Improve Testing and Linkage to Care Among Non-U.S.-Born Persons with Chronic Hepatitis B Virus Infection - Three U.S. Programs, October 2014-September 2017.

Among an estimated 850,000 to 2.2 million persons with chronic hepatitis B virus (HBV) infection in the United States, 70% are non-U.S.-born (1,2). All patients require linkage to care, and approximately 20%-40% require antiviral treatment (3). Without treatment, one in four persons chronically infected with HBV will die prematurely from liver failure, liver cirrhosis, or hepatocellular carcinoma (4). To mitigate morbidity and mortality, CDC funded a cooperative agreement to develop hepatitis B testing and linkage-to-care programs serving non-U.S.-born persons during October 2014-September 2017. This report describes each program's operational services and partnerships with primary care centers, community-based organizations, and public health departments to recruit non-U.S.-born persons for HBV testing using the hepatitis B surface antigen (HBsAg) and link those whose test results were positive to HBV-directed care (medical visit attendance with monitoring of HBV DNA and liver enzyme tests). Among 10,152 program participants, 757 (7.5%) were HBsAg-positive, indicative of chronic HBV infection; among these, 643 (85%) attended ≥1 medical visit, 587 (78%) received HBV-directed care, and 137 (18%) were prescribed antiviral treatment. Among 273 household contacts of HBsAg-positive persons, 39 (14%) had positive test results for HBsAg. Prevalence of current HBV infection was high in this non-U.S.-born population and among household and sexual contacts of HBV-infected persons. HBV testing and linkage to care can be achieved through partnerships with community organizations, health centers, and public health departments.

Development of a portable electrochemical loop mediated isothermal amplification (LAMP) device for detection of hepatitis B virus.

The objective of this study was to develop a simple, inexpensive prototype device for rapid detection of hepatitis B virus (HBV). The device was able to simultaneously amplify, detect and quantify the target HBV DNA. The system was fabricated from a custom-made electrochemical set-up of which the temperature was thermostatically controlled by a water bath. Real-time monitoring of HBV DNA was accomplished by measuring the response of redox indicator in the reaction mixture. Concentration of HBV DNA in the samples was determined from the peak high ratio (PHR) and threshold time relationship. The signal was processed by sigmoidal model fitting to enhance the accuracy of the results. Key parameters including concentrations of redox indicator and reaction temperatures were optimized. Sensitivity and specificity of the method toward HBV DNA were evaluated. The prototype was capable of real-time amplification and detection of HBV DNA with concentration as low as 6.18 fg μl−1. The test showed high specificity against HBV DNA. The system was also able to detect HBV positive serum directly with simple thermal pretreatment instead of tedious DNA extraction. The electrochemical set-up was compatible with microfluidic platforms and can be readily adapted for efficient and high throughput point-of-care (POC) diagnosis of HBV.