Risk of Hepatitis B and Efficacy of Treatment with Lamivudine in Patients Undergoing Allogeneic Stem Cell Transplant.

Abstract Hepatitis B virus (HBV) positive patients undergoing allogeneic stem cell transplantation (allo-SCT) and recipients of allo-SCT from HBV positive donors are at risk of hepatitis reactivation and fatal liver failure. Prophylaxis with lamivudine (LAM) in this setting is still unclear. Since 2005 patients undergoing allo-SCT at risk of HBV reactivation at our Center were treated with LAM prophylaxis to prevent hepatitis B reactivation. Ninety-seven patients undergoing allo-SCT between 1999 and 2007 entered the study. Only 84 patients with a follow-up longer than 3 months (median 17 months, range 3–87) were analysed. Patients, median age of 51 years (21–66), were transplanted for multiple myeloma (50), acute myeloid leukemia (14), chronic lymphatic leukemia (8), lymphoma (7), chronic myeloproliferative disease (4) and aplastic anemia (1). The conditioning regimens consisted of busulfan-cyclophosphamide (7), thiothepa-cyclophosphamide (11), and 2 Gy total body irradiation +/− fludarabine (64); 2 patients received 2 allo-SCT from the same donor for disease progression. Stem cell source was peripheral blood in 83 patients and bone marrow in 1. Sixty-five patients had a HLA-matched sibling donor and 19 an unrelated donor. Sixty subjects were not considered at risk of HBV reactivation (recipients hepatitis B surface antigen -HBsAg- and anti-hepatitis B core antigen antibodies -antiHBc- negative, with donors HBsAg-negative). Of note, 4 donors were antiHBc-positive. None of them experienced HBV related hepatitis during follow-up. The other 24 patients were considered at risk and divided in 3 groups: Group A: 2 HBsAg-negative recipients from HBsAg-positive donors; Group B: 1 HBsAg-positive recipient from negative donor; Group C: 21 antiHBc-positive recipients from 5 positive and 16 negative donors. Group A: Recipients were treated with LAM. None of them developed hepatitis B at a follow up of 24 and 18 months, respectively, and serum HBV-DNA remained undetectable. Group B: One patient with pre-transplant HBV-DNA of 19500 UI/mL received LAM. HBV-DNA became negative 3 months after allo-SCT and the patient did not develop acute hepatitis after a follow-up of 10 months. Group C: Twelve patients were not treated and 9 received prophylactic LAM for a median time of 11 months (range 6–29). Of these, one discontinued LAM after 8 months due to intolerance. Hepatitis developed in 3 untreated patients (2 patients undergoing allo-SCT before 2005 and 7 months after LAM discontinuation in the subject who stopped prophylactic LAM) and in none of the patients on prophylaxis. No detectable serum HBV-DNA was observed in patients on LAM prophylaxis. Two/3 patients with hepatitis received allo-SCT from antiHBc-negative donors. In conclusions, this retrospective study confirms: a null risk of hepatitis B in HBsAg and antiHBc-negative recipients, transplanted with HBsAg-negative donors, regardless of donor’s antiHBc serology; a significant (23%) risk of hepatitis B in antiHBc-positive recipients from negative donors, untreated with prophylactic LAM; the efficacy of prophylactic LAM in HBsAg-negative and antiHBc-positive recipients; the efficacy of LAM in controlling HBV replication and hepatitis B reactivation in both HBsAg-positive recipients from negative donors and in HBsAg-positive donors used in negative recipients.

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Evaluation of a Hepatitis B Virus Reactivation Prevention Program in Lymphoma Patients Receiving Immunochemotherapy

Blood ◽

10.1182/blood.v128.22.1801.1801 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1801-1801

Author(s):

Blanca Sanchez-Gonzalez ◽

Montserrat Garcia-Retortillo ◽

Teresa Murcia ◽

Mariana Ferraro ◽

Francesc Garcia-Pallarols ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Hbv Dna ◽

Hbv Reactivation ◽

Antiviral Prophylaxis ◽

B Virus ◽

Group A ◽

Chronic Hbv ◽

Group B

Abstract INTRODUCTION Chemotherapy-induced hepatitis B virus (HBV) reactivation is a well-recognized complication and is a potentially life-threatening condition in cancer patients with chronic HBV (hepatitis B surface antigen [HBsAg]-positive). Rituximab has been associated with an increase in HBV reactivation in chronic HBV patients (45%) and even in patients with resolved infection (HBsAg negative and hepatitis B core antibody [anti-HBc]-positive (22%); however, the reported frequency varies among different studies. Current guidelines for management of chronic HBV recommend routine antiviral HBV prophylaxis with lymphoma before starting chemotherapy. In contrast, there is little evidence-based consensus regarding patients with resolved HBV infection. Aim: To analyze the incidence of HBV reactivation and the role of antiviral HBV prophylaxis in lymphoma patients with chronic HBV or resolved HBV treated with chemotherapy, immunotherapy or immunochemotherapy managed according to our institutional HBV guidelines. Secondary endpoints were to analyze the incidence of HBV in this population and HBV guidelines adherence. PATIENTS AND METHODS Lymphoma patients with chronic HBV or resolved HBV in a single center. HBV viral status definitions: Active Chronic HBV infection: HBsAg positive, anti-HBc positive and HBV DNA >2000 IU/mL; Inactive Carriers: HBsAg positive, Anti-HBc positive, HBV DNA undetectable or <2000 IU/mL with normal transaminases; Resolved HBV: HBsAg negative, anti-HBc positive, HBV DNA undetectable. HBV reactivation was defined as increased serum HBV DNA (≥1 log10), regardless of liver biochemistry or HBsAg status. Institutional HBV guidelines: serum samples were collected at baseline for HBsAg and anti-HBc testing in all lymphoma patients. Patients were evaluated by a hepatologist if any of them fulfilled HBV viral status definition. Baseline at screening and monitoring every 3 months during therapy and up to 24 months after completing therapy (assessment of liver biochemistry, serum HBV DNA, HBsAg and anti-HBs levels). Specific prophylaxis strategies according to HBV status: Group A (Active chronic HBV): treatment for HBV; Group B (Inactive carriers): antiviral HBV prophylaxis; Group C (Resolved HBV): antiviral HBV prophylaxis if rituximab containing-therapy or follow-up only if rituximab-free therapy. HBV antiviral prophylaxis was started before therapy and finished 12 months after completing therapy. RESULTS From January 2012 to January 2015, 227 lymphoma patients received chemotherapy or immunochemotherapy. 142 (63%) patients received rituximab-containing therapy. 43 (19%) patients were anti-HBc positive. Group A: 2 (1%) patients; Group B: 2 (1%) patients; Group C: 39 (17%) patients. 14 (6%) patients have coinfection with hepatitis C virus and 12 (5%) patients co-infection with human immunodeficiency virus (HIV). Adherence to HBV guidelines was 90%. Patients in Group A (n=2) and B (n=2) received antiviral treatment/prophylaxis before starting therapy. In the Group C, 16 (41%) patients underwent only follow-up and 23 (59%) patients received HBV antiviral prophylaxis (lamivudine in 4, entecavir in 8 and tenofovir in 11). Median duration of HBV prophylaxis was 18 months (95% CI: 16-19 months). After a median follow-up of 21 months, 2 patients developed HBV reactivation during lymphoma treatment: 1 from group B (reactivation rate of 50%) and 1 from group C (reactivation rate of 3%). Both patients had received rituximab-containing treatment and both developed HBV reactivation (without hepatitis flare) within the first 6 months after finishing antiviral HBV prophylaxis (delayed HBV reactivation). Outcome was favorable in both patients. Characteristics of HBV reactivation patients are shown in table I. Cumulative incidence of HBV reactivation at 12 and 24 months were 0% and 8%, respectively. CONCLUSION Our strategy of close monitoring patients with chronic HBV or resolved HBV that receive chemotherapy and adding antiviral HBV prophylaxis only in selected patients clearly decrease HBV reactivation. Nevertheless, this strategy may not fully protect patients from late HBV reactivations. Larger validation studies are needed to confirm our data and to establish the best cost-effective strategy in this lymphoma population, especially in the new era of inmunomodulatory drugs of their real involvement in HBV reactivation is unknown. Table 1 Table 1. Disclosures No relevant conflicts of interest to declare.

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Hepatitis B Virus (HBV) Reactivation In Anti-HB Core Antigen (anti-HBc) Positive Patients with Hematological Malignancies: A Prospective Multicenter Study

Blood ◽

10.1182/blood.v116.21.4911.4911 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4911-4911

Author(s):

Maria Basso ◽

Stefan Hohaus ◽

Giulia Bosco ◽

Antonio Grieco ◽

Luca Laurenti ◽

...

Keyword(s):

At Risk ◽

Hepatitis B ◽

Immunosuppressive Therapy ◽

Hematological Malignancies ◽

Hbv Dna ◽

Core Antigen ◽

Hbv Reactivation ◽

Antiviral Prophylaxis ◽

Allogeneic Hsct

Abstract Abstract 4911 Patients with haematological malignancies and overt hepatitis B (HB) infection defined by the presence of HB surface antigen (HBsAg) are at risk of hepatitis reactivation, and antiviral prophylaxis is generally recommended. HBV reactivation can also occur during immunosuppressive therapy in patients who are HBsAg negative, but are positive for antibodies to HB core antigen (anti-HBc) which suggests prior contact with HBV and potential occult infection. The risk of HBV reactivation for these patients who have evidence of viral clearance (HBV-DNA negative) and developed potential immunity (anti-HBs positive) is not clear, and there are no clear guidelines for prophylaxis in this subset of patients. We therefore performed a multicenter prospective observational study to determine the risk of HBV seroreversion in anti-HBc positive patients with or without anti-HBs and with hematological malignancies undergoing intensive immunosuppressive chemotherapy and/or hematopoietic stem cell transplantation (HSCT). Patients underwent monitoring of HBV serum markers including HBV-DNA serum levels, while patients who started antiviral prophylaxis concomitant to the cytotoxic therapy were excluded. Between 1/2008 and 12/2008, 25 consecutive HBsAg -/antiHBc +/antiHBs + patients (pts) from 3 hematological centers were enrolled into the study (20 pts with lymphoma, 2 pts with acute myeloid leukaemia, 3 with myeloma). Before starting anticancer therapy, all pts had undetectable HBV-DNA levels, 21 were anti-HBs positive, and 12 had also anti-HBe. Moreover, 3 pts had HCV co-infection. All patients underwent intense immunosuppressive therapy including rituximab in 15 pts, and HSCT in 10 pts (7 autologous and 3 allogeneic). HBV markers were monitored during immunosuppressive treatment and for 18 months after end of therapy. At present, 18 pts have completed the planned follow-up period, and other 7 pts have at least 12 months of post-treatment follow-up. Among the 25 patients, we observed 3 cases of seroreversion with positive HBV-DNA levels. All 3 seroversions occurred in patients following allogeneic HSCT despite high anti-HBs levels at baseline. The 3 seroreverted patients showed a progressive decline in anti-HBs titers during the phase of monitoring, and HBV reactivated between the 7th and 9th month after allogeneic HSCT. The pts responded to treatment with antinucleoside analogues (entecavir in 2 cases, lamivudine in 1 case), i.e. HBV-DNA decreased of at least 1 log within three months from treatment start. Moreover, we detected one case of transient anti-HBs disappearance, and one case of persistent anti-HBe loss without seroreversion. None of the HCV co-infected pts presented acute hepatitis. No seroreversions were observed in 15 lymphoma patients undergoing immunochemotherapy including rituximab. In conclusion, patients with occult HBV infection are at risk of HBV reactivation during continuous immunosuppressive therapy following allogeneic HSCT even in the presence of anti-HBs levels at baseline, while the risk appears low in patients undergoing transient immunosuppressive therapy, as immunochemotherapy including rituximab, for the treatment of lymphoma. Disclosures: No relevant conflicts of interest to declare.

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Hepatitis B (HBV) Reactivation Rate and Fate Among Multiple Myeloma Patients Receiving Lenalidomide Containing Regimens: A Single Center Experience

Blood ◽

10.1182/blood.v126.23.5377.5377 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5377-5377 ◽

Cited By ~ 2

Author(s):

Pinar Ataca ◽

Erden Atilla ◽

Ekin Kircali ◽

Ramazan Idilman ◽

Meral Beksac

Keyword(s):

Stem Cell ◽

Hepatitis B ◽

Partial Response ◽

Stem Cell Transplantation ◽

Retrospective Analysis ◽

Cell Transplantation ◽

Hbv Dna ◽

Hbv Reactivation ◽

Hepatitis B Reactivation ◽

Lamivudine Prophylaxis

Abstract Introduction: Reactivation of HBV refers to an increase in hepatitis B virus replication in a patient with inactive or resolved HBV. Reactivation of HBV replication has been reported in 20% to 50% of untreated HBV carriers undergoing immunosuppressive or cancer chemotherapy. Bortezomib has been reported to induce viral reactivation(5.9% HBV reactivation rate)(Liu et al). Herein, we aim to present the rate and fate of HBV reactivation among myeloma patients who have received lenalidomide containing protocols. Patients and Methods: We have evaluated 142 MM patients diagnosed between 2003-2014 who received lenalidomide during their treatment schedules whether for induction, relapse or post-induction maintenance treatment. 92 patients received 25 mg/day lenalidomide with Dexamethasone, 50 received at 10 mg/day as single agent. To be eligible for the analysis a minimum three months duration of treatment and no active hepatitis were required. Hepatitis B serology is rechecked before autologous peripheral stem cell transplantation and if liver enzyme abnormality occured. The hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), hepatitis B surface antibody (anti-HBs), hepatitis B e-antigen (HBeAg), hepatitis B e-antibody (AntiHBe) are detected by Chemiluminescence by ARCHITECT lab analyzers using commercially available kits (Abbott, USA). HBV-DNA titers are determined by quantitative PCR. Results: The median age of 142 MM patients was 56 (range, 42-77). 79 of patients were male (56%). ISS scores at diagnosis were as follows: ISS I/II/III: 51 (36%),57 (40%), 34 (24%). At the initiation of treatment 11 patients had negative HbsAg, positive AntiHBe, AntiHBcIgG, AntiHBs with normal liver function tests. Lamivudine prophylaxis was administered to these naturally immune 11 patients. One of these eleven patients and five patients who had no prior viral exposure had hepatitis B reactivation (4.2%) (Table). All these patients had hypogamaglobulinemia at diagnosis and had received bortezomib prior to lenalidomide. One patient had a history of dialysis. Four patients had received dexamethasone treatment in addition to lenalidomide. After treatment of tenofovir, HBV DNA titers decreased in all and disappeared among three of the six patients. Lenalidomide treatment was interrupted in three of the patients due to progression of disease. One patient who received a second stem cell transplantation for a secondary refractory disease had a progression to cirrhosis following high dose Melphalan. Conclusion: In the current retrospective analysis we observed reactivation of hepatitis in 4.2% of patients who happened to have high ISS scores and were heavily treated previously. Only one patient had activation under prophylaxis. Lenalidomide can be associated with a low reactivation rate of HBV. Hepatitis B reactivation was detected more with lenalidomide and dexamethasone treated patients. The reactivation rate observed in this retrospective analysis is lower than those published previously and may account for the immune modulation effects of lenalidomide and close follow-up. Table 1. Patient Characteristics (CR: Complete Response, PR: Partial Response, PD: Progressive Disease, VGPR: Very Good Partial Response) Patient Age (years)/MM type/ISS Treatment lines/Bortezomib prior/Lamivudine prophylaxis Hepatitis B markers at diagnosis Hepatitis B markers after revlimid treatment Treatment/Time to reactivation after lenalidomide (months) OS (months)/Status of disease 56/Lambda/2 3/+/- HBsAg-, HBeAg-AntiHBeAg-,AntiHBc-AntiHBS+ HBsAg+,HBeAg+,AntiHBeAg, AntiHBc+,AntiHBS- Tenofovir/11 20/CR 74/ IgGkappa/2 4/+/- HBsAg-,HBeAg-AntiHBeAg-,AntiHBc-AntiHBS+ HBsAg+,HBeAg+,AntiHBeAg-AntiHBc+,AntiHBS- Tenofovir/18 52/PR 45 /IgGkappa/3 4/+/- HBsAg-HBeAg-AntiHBeAg-AntiHBc-AntiHBS+ HBsAg+,HBeAg+,AntiHBeAg-AntiHBc+,AntiHBs- Tenofovir/16 58/VGPR 61/ IgGkappa/3 5/+/- HBsAg-,HBeAg-AntiHBeAg-,AntiHBc-AntiHBS+ HBsAg+,HBeAg+,AntiHBeAg-AntiHBc+,AntiHBS- Tenofovir/13 45/VGPR 43/IgAlambda/3 6/+/+ HBsAg-,HBeAg-AntiHBeAg+,AntiHBc-AntiHBS+ HBsAg+,HBeAg+,AntiHBeAg-AntiHBc+,AntiHBS- Tenofovir/7 58/PD 67/ IgGkappa/3 5/+/- HBsAg-HBeAg-AntiHBeAg-AntiHBc-AntiHBS+ HBsAg+,HBeAg+,AntiHBeAg-AntiHBc+,AntiHBS- Tenofovir/12 66/PD Disclosures No relevant conflicts of interest to declare.

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Pathological changes of liver one year later in CHB patients with negative HBV DNA

Infectious Agents and Cancer ◽

10.1186/s13027-019-0265-2 ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 1

Author(s):

Wu Shanshan ◽

Du Xinfang ◽

Yu Shuihong ◽

Lai Kecong ◽

Qi Jinjin ◽

...

Keyword(s):

Hepatitis B ◽

Hepatitis B Surface Antigen ◽

Hbv Dna ◽

Hepatitis B E Antigen ◽

Viral Therapy ◽

Group A ◽

One Year ◽

Group B ◽

Anti Viral Therapy

Abstract Background In this study, we aim to determine the hepatic pathological changes in HBV DNA-negative chronic Hepatitis B (CHB) patients after 12-month antiviral therapy. Methods Blood routine indicators including platelet count (PLT) and white blood cell (WBC) were determined. The coagulation function was evaluated by determining the prothrombin time (PT) and prothrombin time activity (PTA), together with the HBV DNA quantification and alpha fetoprotein (AFP). The virology data included hepatitis B surface antigen (HBsAg)/antibodies against hepatitis B surface antigen (anti-HBs), hepatitis B e antigen (HBeAg)/antibodies against hepatitis B e antigen (anti-HBe) and antibodies against hepatitis B core antigen (anti-HBc) were tested. Pathological assay was performed to the liver puncture tissues. Based on the HBV DNA data in the 12-month follow-up of the cases that received anti-viral therapy during this time, the experimental group was divided into group A (HBV DNA negative at the baseline level, HBV DNA negative after 12 months, N = 79) and group B (HBV DNA negative at the baseline level, HBV DNA turning to be positive after 12 months, N = 13). Statistical analysis was performed on the each test index of the two groups. Results The inflammation grade of group A showed significant improvement after 12-month treatment (P < 0.05). The pathological inflammation grade of group B was increased after one year, and the liver function indices and the PTA (P < 0.05) levels were all increased. Pathological results indicated that the proportion of disease progression in group A was decreased after 12-month follow-up while that proportion was increased in group B. Significant differences were noticed in AFP levels between the patients with progression in group A and those with progression in group B. Conclusion Negative HBV DNA does not mean a controlled hepatitis B. Hepatitis B patients transferred to HBV DNA positivity during the anti-viral therapy are easily to show disease progression, and then special attention should be paid to the HBV DNA monitoring. Meanwhile, close monitoring to the changes of liver function, PTA and AFP levels may help to detect changes on the disease in a timely manner.

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

Blood ◽

10.1182/blood-2018-99-119079 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2256-2256 ◽

Cited By ~ 1

Author(s):

Shen Li ◽

Allaa Ali ◽

Alexander Lawandi ◽

Myriam Fernandez ◽

Caroline Rousseau ◽

...

Keyword(s):

At Risk ◽

Hepatitis B ◽

Research Funding ◽

Health Centre ◽

Hbv Dna ◽

Hbv Reactivation ◽

Patients At Risk ◽

Cancer Network ◽

Hbv Screening

Abstract 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. Disclosures Assouline: 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.

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Hepatitis B Virus Reactivation in Lymphoma Patients With Prior Resolved Hepatitis B Undergoing Anticancer Therapy With or Without Rituximab

Journal of Clinical Oncology ◽

10.1200/jco.2008.18.0182 ◽

2009 ◽

Vol 27 (4) ◽

pp. 605-611 ◽

Cited By ~ 436

Author(s):

Winnie Yeo ◽

Tung C. Chan ◽

Nancy W.Y. Leung ◽

Wai Y. Lam ◽

Frankie K.F. Mo ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Surface Antigen ◽

Hepatitis B Surface Antigen ◽

B Cell Lymphoma ◽

Anticancer Therapy ◽

Hbv Dna ◽

Core Antigen ◽

Hbv Reactivation ◽

B Virus

Purpose Reactivation of hepatitis B virus (HBV) infection is a well-recognized complication in cancer patients with chronic HBV (hepatitis B surface antigen [HBsAg] positive) undergoing cytotoxic chemotherapy. In patients who have resolved HBV (HBsAg negative and antibody to hepatitis B core antigen [anti-HBc] ± antibody to hepatitis B surface antigen [anti-HBs] positive), such incidence has been much less common until recent use of rituximab. In this study on HBsAg-negative/anti-HBc–positive lymphoma patients, the objectives were to determine the HBV reactivation rate in patients treated with rituximab-containing chemotherapy and to compare it with the rate in patients treated without rituximab. Patients and Methods Between January 2003 and December 2006, all patients diagnosed with CD20+ diffuse large B-cell lymphoma (DLBCL) had HBsAg determined before anticancer therapy. They were treated with either cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) alone or rituximab plus CHOP (R-CHOP). HBsAg-negative patients had anti-HBc determined; serum was stored for anti-HBs and HBV DNA. All patients were observed for HBV reactivation, which was defined as detectable HBV DNA with ALT elevation during and for 6 months after anticancer therapy. Results Among 104 CD20+ DLBCL patients, 80 were HBsAg negative. Of the latter, 46 patients (44.2%) were HBsAg negative/anti-HBc positive; 25 of these patients were treated with CHOP, and none had HBV reactivation. In contrast, among the 21 patients treated with R-CHOP, five developed HBV reactivation, including one patient who died of hepatic failure (P = .0148). Exploratory analysis identified male sex, absence of anti-HBs, and use of rituximab to be predictive of HBV reactivation. Conclusion Among HBsAg-negative/anti-HBc–positive DLBCL patients treated with R-CHOP, 25% developed HBV reactivation. Close monitoring until at least 6 months after anticancer therapy is required, with an alternative approach of prophylactic antiviral therapy to prevent this potentially fatal condition.

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Hepatitis B Reactivation in Patients With Previous Hepatitis B Virus Exposure Undergoing Rituximab-Containing Chemotherapy for Lymphoma: A Prospective Study

Journal of Clinical Oncology ◽

10.1200/jco.2014.56.7081 ◽

2014 ◽

Vol 32 (33) ◽

pp. 3736-3743 ◽

Cited By ~ 182

Author(s):

Wai-Kay Seto ◽

Thomas S.Y. Chan ◽

Yu-Yan Hwang ◽

Danny Ka-Ho Wong ◽

James Fung ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Significant Risk ◽

Hbv Dna ◽

High Rate ◽

Chinese Patients ◽

Core Antigen ◽

Hbv Reactivation ◽

B Virus ◽

Cumulative Rate

PurposePatterns of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg) –negative, antihepatitis B core antigen antibody (anti-HBc) –positive patients with lymphoma receiving rituximab-containing chemotherapy have not been well described.Patients and MethodsHBsAg-negative, anti-HBc–positive Chinese patients with undetectable serum HBV DNA (< 10 IU/mL), diagnosed with hematologic malignancies and receiving rituximab-containing chemotherapy, were prospectively monitored every 4 weeks for up to 2 years. Entecavir was started when HBV reactivation (defined as detectable HBV DNA) was encountered.ResultsAmong 260 patients receiving rituximab-containing chemotherapy, 63 patients (24.2%) who were HBsAg negative and anti-HBc positive underwent follow-up for a median of 70 weeks (range, 6 to 104 weeks). The 2-year cumulative rate of HBV reactivation was 41.5%, occurring at a median of 23 weeks (range, 4 to 100 weeks) after rituximab treatment. The median HBV DNA level at reactivation was 43 IU/mL (range, 14 to 920 IU/mL). A baseline undetectable antibody to HBsAg (anti-HBs; < 10 mIU/mL) was the only significant risk factor that was positively associated with HBV reactivation (hazard ratio, 3.51; 95% CI, 1.37 to 8.98; P = .009). Patients with negative baseline anti-HBs, compared with those with positive anti-HBs, had a significantly higher 2-year cumulative rate of HBV reactivation (68.3% v 34.4%; P = .012). At HBV reactivation, all patients had normal ALT, and all patients but one were HBsAg negative. Entecavir successfully controlled HBV reactivation in all patients.ConclusionA high rate of HBV reactivation was observed in HBsAg-negative, anti-HBc–positive patients undergoing rituximab-containing chemotherapy, with the risk of reactivation significantly higher in anti-HBs–negative patients. Periodic HBV DNA monitoring was an effective strategy in preventing HBV-related complications.

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Low Risk of Hepatitis B Virus Reactivation in HBsAg-negative/Anti-HBc–positive Carriers Receiving Rituximab for Rheumatoid Arthritis: A Retrospective Multicenter Italian Study

The Journal of Rheumatology ◽

10.3899/jrheum.151105 ◽

2016 ◽

Vol 43 (5) ◽

pp. 869-874 ◽

Cited By ~ 27

Author(s):

Valentina Varisco ◽

Mauro Viganò ◽

Alberto Batticciotto ◽

Pietro Lampertico ◽

Antonio Marchesoni ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Hepatitis B Surface Antigen ◽

Hbv Dna ◽

Hbv Infection ◽

Core Antigen ◽

Hbv Reactivation ◽

Serum Hbsag ◽

B Virus

Objective.Patients with resolved hepatitis B virus (HBV) infection, i.e., hepatitis B surface antigen (HBsAg)-negative/antihepatitis B core antigen (anti-HBc)-positive, undergoing rituximab (RTX)-based chemotherapy for hematological malignancies without anti-HBV prophylaxis are at risk of HBV reactivation, but the risk in such patients receiving RTX for rheumatological disorders is not clear. We evaluated this risk in HBsAg-negative/anti-HBc–positive patients with rheumatoid arthritis (RA) undergoing RTX without prophylaxis.Methods.Thirty-three HBsAg-negative/anti-HBc–positive outpatients with RA with undetectable HBV DNA by sensitive PCR assay [73% women, median age 60 years, 85% with HBsAg antibodies (anti-HBs), 37% with antihepatitis B envelope antigen] received a median of 3 cycles of RTX (range 1–8) over 34 months (range 0–80) combined with disease-modifying antirheumatic drugs (DMARD) without prophylaxis. All underwent clinical and laboratory monitoring during and after RTX administration, including serum HBsAg and HBV DNA measurements every 6 months or whenever clinically indicated.Results.None of the patients seroreverted to HBsAg during RTX treatment, but 6/28 (21%) showed a > 50% decrease in protective anti-HBs levels, including 2 who became anti-HBs–negative. One patient (3%) who became HBV DNA-positive (44 IU/ml) after 6 months of RTX treatment was effectively rescued with lamivudine before any hepatitis flare occurred. Among the 14 patients monitored for 18 months (range 0–70) after RTX discontinuation, no HBV reactivation was observed.Conclusion.The administration of RTX + DMARD in patients with RA with resolved HBV infection leads to a negligible risk of HBV reactivation, thus suggesting that serum HBsAg and/or HBV DNA monitoring but not universal anti-HBV prophylaxis is justified.

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The Change of Quantitative of HBeAg Can Predict the Efficacy of Peg-IFN-α 2a in HBeAgpositive CHB Patients

Infection International ◽

10.1515/ii-2017-0053 ◽

2013 ◽

Vol 2 (3) ◽

pp. 127-131

Author(s):

Yong-jian Ji ◽

Wan-hua Ren ◽

Fei-fei Li ◽

Jian-ting Fang ◽

Xi-zhen Sun ◽

...

Keyword(s):

Hepatitis B ◽

Treatment Efficacy ◽

Combined Therapy ◽

Statistical Significance ◽

Hbeag Seroconversion ◽

Hbv Dna ◽

Hbv Cccdna ◽

Group A ◽

The Difference ◽

Group B

Abstract Objective To investigate the quantitation of hepatitis B e antigen (HBeAg) at week 24 in predicting the efficacy of pegylated-interferon alfa-2a (Peg-IFN-α 2a) in HBeAg-positive chronic hepatitis B (CHB) patients at week 48 and to find a useful predictor for treatment efficacy and investigate individualized treatment of antiviral therapy. Methods Ninety-six HBeAg-positive CHB patients with detectable HBeAg who were treated with Peg-IFN-α 2a were enrolled in this trial. They were categorized into 3 groups according to the changes of HBeAg in week 24: HBeAg decline > 2 log10 group (group A), HBeAg decline between 1 1og10 - 2 log10 (group B), HBeAg decline < 1 log10 group (group C), and group C was randomly distributed into C1 and C2. The patients in group A, group B, and group C1 continued the original therapy and the patients in group C2 were given lamivudine plus Peg-IFN-α 2a for 24 weeks. At week 48, the treatment efficacy and hepatitis B virus covalently closed circular DNA (HBV cccDNA) in liver biopsies were analyzed. Results At week 48, mean reduction of serum HBV DNA: group A: 5.8 log10 copies/ml, group B: 3.8 log10 copies/ml, group C1: 2.8 log10 copies/ml, group C2: 5.7 log10 copies/ml, the reduction of HBV DNA in group A was greater than groups B and C1 (P < 0.01), that in group C1 was greater than group C2 (P < 0.01), the difference between groups B and C1 had no statistical significance (P = 0.19). Mean reduction of HBeAg: group A: 2.7 log10S/CO, group B: 1.9 log10S/CO, group C1: 0.9 log10S/CO, group C2: 1.5 log10S/CO, the difference among groups A, B and C1 and between groups C1 and C2 were statistically significant (P < 0.01). At week 48, HBV DNA undetectable rate in group A, group B, group C1 and group C2 were 87.5%, 34.5%, 17.4% and 81.9%, respectively, the rate in group A was greater than groups B and C1 (P < 0.01)，that in group C1 was greater than group C2 (P < 0.01). HBeAg seroconversion rate were 75.0%, 24.1%, 13.0% and 22.7%, respectively, that in group A was greater than groups B and C1 (P < 0.01). Group A had lower cccDNA in liver tissue than group B and group C1 (P < 0.01). The difference of HBV cccDNA between groups B and C1 and that between groups C1 and C2 had no statistical significance. Conclusions HBeAg decline > 2 log10 at week 24 in Peg-IFN-α 2a-treated hepatitis B patients suggested a better efficacy at week 48; HBeAg decline < 2 log10 at week 24 suggests a worse efficacy at week 48, the combined therapy of Peg-IFN-α and lamivudine could improve the clinical responses. The change of quantitative of HBeAg at week 24 may be used as a predictor of treatment effects at week 48.

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Abatacept is second to rituximab at risk of HBsAg reverse seroconversion in patients with rheumatic disease

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-220774 ◽

2021 ◽

pp. annrheumdis-2021-220774

Author(s):

Ming-Han Chen ◽

I-Cheng Lee ◽

Ming-Huang Chen ◽

Ming-Chih Hou ◽

Chang-Youh Tsai ◽

...

Keyword(s):

Risk Factors ◽

Hepatitis B ◽

Hepatitis B Surface Antigen ◽

Core Antigen ◽

Hbv Reactivation ◽

Lower Baseline ◽

B Virus ◽

Independent Risk Factors ◽

Free Status

BackgroundHepatitis B surface antigen (HBsAg) reverse seroconversion (RS) can happen in patients with rheumatoid arthritis (RA) with resolved hepatitis B (RHB) undergoing biological disease-modifying antirheumatic drugs (bDMARDs). But the incidence and risk factors need to be delineated.MethodsFrom 2003 to 2019, 1937 patients with RA with available HBsAg and antibody to hepatitis B virus (HBV) core antigen data were retrospectively reviewed, and 489 patients with RHB undergoing bDMARDs treatment were identified. Factors associated with HBsAg RS were analysed.ResultsDuring 67 828 person-months of follow-up, 27 (5.5%) patients developed HBsAg RS after bDMARD treatment. As compared with those without HBsAg RS, patients with HBsAg RS were older, had lower frequency of antibody to HBsAg (anti-HBs), and lower baseline anti-HBs levels. In multivariate analysis, rituximab, abatacept and baseline negative for anti-HBs were the independent risk factors for HBsAg RS (adjusted HR: 87.76, 95% CI: 11.50 to 669.73, p<0.001; adjusted HR: 60.57, 95% CI: 6.99 to 525.15, p<0.001; adjusted HR: 5.15, 95% CI: 2.21 to 12.02, p<0.001, respectively). The risk of HBsAg RS was inversely related to the level of anti-HBs. Both rituximab and abatacept might result in anti-HBs loss, and abatacept had a cumulative incidence of HBsAg RS of 35.4%–62.5% in patients with low titers or negative of anti-HBs.ConclusionsNot only rituximab, but also abatacept has a high risk of HBV reactivation in patient with RA with RHB. Anti-HBs positivity cannot confer HBV reactivation-free status if the anti-HBs levels are not high enough for patients with RHB on rituximab and abatacept treatment.

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