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

Blood ◽  
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.

scholarly journals Hepatitis B virus Reactivation in Patients Receiving Tocilizumab for Rheumatoid Arthritis: A Long‐term, Retrospective Observational Study

2020 ◽  
Author(s):  
Kuo Meng Hsuan ◽  
Chih-Wei Tseng ◽  
Ming-Chi Lu ◽  
Chien-Hsueh Tung ◽  
Kuo-Chih Tseng ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbv Reactivation ◽  
Antiviral Prophylaxis ◽  
Virus Reactivation ◽  
B Virus ◽  
Hepatitis Flare

Abstract Aim To investigate the risk of hepatitis B virus (HBV) reactivation in patients undergoing long-term tocilizumab (TCZ) therapy for rheumatoid arthritis (RA). Method From January 2011 through August 2019, a total of 134 RA patients who received TCZ at Dalin Tzu Chi Hospital were screened. Patients were excluded if they were < 20 years, without complete data, or received TCZ for less than 3 months. A total of 97 patients were enrolled in this retrospective study. Clinical data, co-medications, and the occurrence of HBV reactivation were recorded. Results Of the 97 enrolled patients, 7 were HBsAg+ (7.2%), 64 were HBsAg−/HBcAb+ (61%) and 26 were HBsAg−/HBcAb+ (26.8%). The median disease follow-up time was 9 years (range, 1–18 years). TCZ was administered for a median of 29 months (range, 3–91 months). Four patients (4.1%) experienced HBV reactivation after TCZ therapy. Of the 7 HBsAg+ patients, 4 received antiviral prophylaxis and had no HBV reactivation; the remaining 3 patients had no antiviral prophylaxis, and all 3 (100%) experienced early HBV reactivation and hepatitis flare (median time to event, 6 months; range, 5–8 months). Hyper-bilirubinemia occurred in 2 of these 3 patients, with mild prothrombin time prolongation in one. After salvage entecavir treatment, all patients had a favorable outcome. Of the 64 HBsAg−/HBcAb+ patients, only one became positive for serum HBV DNA (2.5 × 10 7 IU/mL) after 18 months of TCZ treatment (1.6%; 1/64). This patient was immediately treated with entecavir, which prevented hepatitis flare. Conclusions HBsAg+ RA patients undergoing TCZ treatment are at high risk of HBV reactivation, which is prevented by antiviral prophylaxis. HBsAg−/HBcAb+ patients also are at risk of HBV reactivation. Although their risk of reactivation is lower than that of HBsAg+ patients, strict monitoring of their HBV status is still necessary.

Lamivudine therapy for prevention of immunosuppressive-induced hepatitis B virus reactivation in hepatitis B surface antigen carriers

Blood ◽  
2002 ◽  
Vol 100 (2) ◽  
pp. 391-396 ◽  
Author(s):  
Oren Shibolet ◽  
Yaron Ilan ◽  
Shmuel Gillis ◽  
Ayala Hubert ◽  
Daniel Shouval ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Immunosuppressive Therapy ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
Hbv Reactivation ◽  
Hbsag Carriers ◽  
B Virus ◽  
Lamivudine Prophylaxis

Abstract Viral reactivation in hepatitis B surface antigen (HBsAg) carriers undergoing immunosuppressive therapy is well documented. To evaluate the role of lamivudine prophylaxis in Hepatitis B virus (HBV) carriers treated with immunosuppression for nonhepatic disorders, we reviewed our experience between 1997 and 2000 at Hadassah University Hospital (Jerusalem, Israel). Controls were patients who were HBV carriers and who, between 1990 and 1995, were treated for hematological malignancies but were not treated with lamivudine. Eighteen HBsAg-positive patients were treated with immunosuppression. Fourteen were males, with a mean age of 48 years. Eleven patients had lymphoma; 2 had colonic adenocarcinoma; and 5 had cryoglobulinemia, enophthalmitis, vasculitis, malignant histocytosis, or ulcerative colitis. Fourteen patients were treated with chemotherapy, and 4 with prolonged high-dose corticosteroids. All patients were HBsAg-positive; 4 had hepatitis B e antigen, and 10 had HBV DNA by polymerase chain reaction. Lamivudine was administered to 13 patients in the treatment group 1 to 60 days (mean, 15 days) before immunosuppressive treatment and continued 0.5 to 24 months (mean, 7 months) following initiation of immunosuppression. Mean follow-up after lamivudine administration was 21 months. Three patients died of lymphoma complications and 10 (77%) survived. None of the patients had clinical or serological evidence of HBV reactivation during or after lamivudine prophylaxis. Of 6 patients who presented with liver function test disturbances, 5 improved during combined lamivudine and immunosuppression treatment. At the end of follow-up, HBV DNA became undetectable in 2 of 10 patients. In 2 patients, seroconversion from HBsAg to anti-HBs was observed. In contrast, 2 of 5 control patients had HBV reactivation. Lamivudine prophylaxis in HBsAg carriers receiving immunosuppressive therapy may prevent HBV reactivation and hepatic failure.

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

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1970-1970
Author(s):  
Luisa Giaccone ◽  
Alfredo Marzano ◽  
Isabel Resta ◽  
Andrea Marengo ◽  
Francesca Fiore ◽  
...  
Keyword(s):  
At Risk ◽  
Stem Cell ◽  
Hepatitis B ◽  
Hbv Dna ◽  
Core Antigen ◽  
Hbv Reactivation ◽  
Hepatitis B Reactivation ◽  
Group A ◽  
Group B

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.

Risk of Hepatitis B Virus (HBV) Reactivation and Role of Anti-Viral Prophylaxis in Lymphoma Patients with Past HBV Infection (HBV Antigen negative but anti-Hepatitis B core antibody positive) Receiving Chemo-Immunotherapy

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3768-3768 ◽  
Author(s):  
Yu Xuan Koo ◽  
Shao Weng Tan ◽  
Bee Huat Tan ◽  
Miriam Tao ◽  
Wan Cheng Chow ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Systemic Treatment ◽  
Hbv Dna ◽  
Hbv Infection ◽  
Hbv Reactivation ◽  
Antiviral Prophylaxis ◽  
Past Infection ◽  
Absolute Increase ◽  
B Virus

Abstract Hepatitis B virus (HBV) infection, defined by the presence of HBV surface antigen (HBsAg), increases the risk of HBV reactivation and current guidelines recommend that patients who are HBV-infected should receive antiviral prophylaxis during and after chemotherapy. As HBV infection is endemic in Asia, a proportion of patients may have had past HBV infection unknowingly. These patients have cleared HBsAg and are HBsAg negative but anti-Hepatitis B core antibody (anti-HBc) positive. The risk of HBV reactivation in lymphoma patients with past HBV infection undergoing immunochemotherapy has not been previously studied. We accrued 430 consecutive patients from our prospectively maintained data-base and an ongoing prospective epidemiological study from May 2006 to May 2008. All patients were tested for HBsAg. Prior to May 2006, anti-HBc test was performed at the discretion of the treating physician. After May 2006, anti-HBc test was performed for all patients. Stored sera from consented patients were genotyped for HBV DNA. Hepatitis attributable to HBV reactivation was defined as an increase in HBV DNA levels of tenfold, or an absolute increase greater than 105 copies/ml in the HBV DNA level. At presentation, characteristics of lymphomas and baseline liver function test in patients with HBV infection were similar to those with past HBV infection. Among the 430 patients tested for HBsAg, the prevalence of HBV infection is 7.2% (31/430). Overall, 233 patients had both tests performed and 80 (34%) were anti-HBc positive only. Among the 80 patients with past HBV infection, 67 patients received systemic treatment. Of these 67 patients, 58 had a HBV DNA test, which was positive in three (5.2%). 46 patients with past HBV infection were treated with rituximab immunochemotherapy. Of these 46 patients, one reactivated and died (1/46; 4.3%); this patient did not receive anti-viral prophylaxis and had undetectable HBV DNA at time of lymphoma diagnosis. Of the 26 patients with HBV infection receiving systemic treatment, 11 (42.3%) reactivated (p<0.0001). 90% of patients with HBV infection received antiviral prophylaxis compared to 10% with past HBV infection. Of note, all 4 patients with HBV infection with mutant HBV on genotyping reactivated despite prophylactic lamivudine usage. The incidence of past HBV infection (34%) is unexpectedly high and a small proportion (5.2%) had occult infection (detectable HBV DNA). These findings have further implications in terms of HBV screening in endemic regions. Our data is the first to suggest that although majority of patients with past infection do not reactivate, the risk is not negligible when rituximab is used (4%). Undetectable HBV DNA does not appear to preclude reactivation. This data is also provocative and suggests that anti-HBc should be routinely tested and those with past infection, with or without detectable HBV DNA, be monitored closely for reactivation. The optimal use of anti-viral prophylaxis, particularly if immunotherapy is given, should be further evaluated. This is particularly relevant in endemic regions where the incidence of past infection is likely to be high. Given the observation that all patients with mutant HBV reactivated despite lamivudine prophylaxis, the optimal anti-viral agents chosen should be further evaluated. Past HBV infection (n=67) HBV–carrier (n=26) p= Prophylactic lamivudine 7 (10.4%) 18 (69.2%) <0.0001 ALT(Baseline) (median/range) 20 (5–118) 21 (6–338) - Received Rituximab 46 (68.7%) 17 (65.4%) 0.8073 Hepatic decompensation 22 (32.8%) 10 (38.5%) 0.633 HBV reactivation 1 (1.5%) 11 (42.3%) <0.0001

scholarly journals Hepatitis B Virus Reactivation Induced by Infliximab Administration in a Patient with Crohn’s Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Yuka Miyake ◽  
Aki Hasebe ◽  
Tetsuya Tanihira ◽  
Akiko Shiraishi ◽  
Yusuke Imai ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Hepatitis B Virus ◽  
Crohn's Disease ◽  
Hepatitis B ◽  
Bowel Disease ◽  
Hbv Dna ◽  
Hbv Reactivation ◽  
B Virus ◽  
Inflammatory Bowel

A 47-year-old man diagnosed with Crohn’s disease was treated with infliximab. He tested negative for hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) but positive for anti-HB core antibody (anti-HBc). He tested positive for hepatitis B virus (HBV-) DNA 3 months after treatment and was administered entecavir. HBV-DNA test showed negative results 1 month later. ALT was persistently within the normal range, and HBV-DNA was persistently negative thereafter despite the continuation of infliximab every 8 weeks. In our hospital, 14 patients with inflammatory bowel disease, who tested negative for HBsAg, were treated with infliximab; 2 of them tested positive for anti-HBs and/or anti-HBc, and HBV reactivation was observed in 1 patient (the present patient). The present case and these findings highlight that careful follow-up is needed in patients with inflammatory bowel disease treated with infliximab who test positive for anti-HBc and/or anti-HBs.

Randomized Controlled Trial of Entecavir Prophylaxis for Rituximab-Associated Hepatitis B Virus Reactivation in Patients With Lymphoma and Resolved Hepatitis B

2013 ◽  
Vol 31 (22) ◽  
pp. 2765-2772 ◽  
Author(s):  
Yi-Hsiang Huang ◽  
Liang-Tsai Hsiao ◽  
Ying-Chung Hong ◽  
Tzeon-Jye Chiou ◽  
Yuan-Bin Yu ◽  
...  
Keyword(s):  
Viral Load ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Controlled Trial ◽  
Control Group ◽  
Hbv Reactivation ◽  
Antiviral Prophylaxis ◽  
B Virus ◽  
To Receive

Purpose The role of antiviral prophylaxis in preventing hepatitis B virus (HBV) reactivation before rituximab-based chemotherapy in patients with lymphoma and resolved hepatitis B is unclear. Patients and Methods Eighty patients with CD20+ lymphoma and resolved hepatitis B were randomly assigned to receive either prophylactic entecavir (ETV) before chemotherapy to 3 months after completing chemotherapy (ETV prophylactic group, n = 41) or to receive therapeutic ETV at the time of HBV reactivation and hepatitis B surface antigen (HBsAg) reverse seroconversion since chemotherapy (control group, n = 39). Results Fifty-eight patients (72.5%) were positive for hepatitis B surface antibody, and HBV DNA was undetectable in 50 patients (62.5%). During a mean 18-month follow-up period, one patient (2.4%) in the ETV prophylactic group and seven patients (17.9%) in the control group developed HBV reactivation (P = .027). The cumulative HBV reactivation rates at months 6, 12, and 18 after chemotherapy were 8%, 11.2%, and 25.9%, respectively, in the control group, and 0%, 0%, and 4.3% in the ETV prophylactic group (P = .019). Four patients (50%) in the control group had HBsAg reverse seroconversion after HBV reactivation. The cumulative HBsAg reverse seroconversion rates at months 6, 12, and 18 since chemotherapy were 0%, 6.4%, and 16.3% in the control group, respectively, which were significantly higher than those in the ETV prophylactic group (P = .032). Patients with detectable or undetectable viral load could develop HBV reactivation and HBsAg reverse seroconversion. Conclusion Undetectable HBV viral load before chemotherapy did not confer reactivation-free status. Antiviral prophylaxis can potentially prevent rituximab-associated HBV reactivation in patients with lymphoma and resolved hepatitis B.

scholarly journals Risk stratification and clinical course of hepatitis B virus reactivation in rheumatoid arthritis patients with resolved infection: final report of a multicenter prospective observational study at Japanese Red Cross Hospital

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Wataru Fukuda ◽  
Tadamasa Hanyu ◽  
Masaki Katayama ◽  
Shinichi Mizuki ◽  
Akitomo Okada ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Risk Stratification ◽  
Scoring System ◽  
Clinical Course ◽  
Hbv Dna ◽  
Hbv Reactivation ◽  
B Virus

Abstract Background The prophylaxis for hepatitis B virus (HBV) reactivation assumes that hepatic injury after reactivation is often rapidly progressive and can evoke fulminant hepatitis. The incidence and prognosis of reactivation in patients with rheumatoid arthritis (RA) may be different from those receiving organ transplantation and cancer chemotherapy. This study aimed to investigate the incidence, risk factors, and clinical course of HBV reactivation and develop a scoring system for risk stratification in RA patients with resolved infection. Methods HBV DNA was measured using real-time polymerase chain reaction, and patient data were collected for 4 years in RA patients with resolved HBV infection who were treated with steroids or synthetic or biologic immunosuppressive drugs. Results Among 1127 patients, HBV DNA was detected in 57 patients (1.65/100 person-years); none of the reactivated patients exhibited worsening of hepatic function. Multivariate logistical analysis revealed that age > 70 years and HB core antibody (HBcAb) positivity alone were independent risk factors for HBV reactivation. HBV DNA ≥ 2.1 log copies/mL was observed in 15 patients (0.43/100 person-years); seven patients were treated with nucleic acid analogs (NAAs), whereas the remaining eight were observed without treatment. Among reactivated cases, 15 cases changed to HBV DNA-negative status spontaneously, whereas 24 cases remained HBV DNA positive < 2.1 log copies/mL during the observation period. We designed the following scoring system: HBV reactivation risk score = 1 × (age > 70 years) + 2 × (HBcAb positivity alone) + 1 × (treatment other than methotrexate monotherapy). This revealed that patients with the highest score had an odds ratio of 13.01 for HBV reactivation, compared to those with the lowest score. Conclusions Rapid progression and poor outcomes after HBV reactivation were not frequent in RA patients with resolved infection. Our new risk scoring system might be useful for screening and optimization of prophylactic treatment by distinguishing patients with significantly lower reactivation risk.

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

2009 ◽  
Vol 27 (4) ◽  
pp. 605-611 ◽  
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.

High Risk of Hepatitis B Virus Reactivation in Isolated Anti-Hbc Positive Patients with B-Cell Lymphoma Receiving Rituximab Containing Chemotherapy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1944-1944
Author(s):  
Hideaki Fujiwara ◽  
Kosei Matsue
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hbv Dna ◽  
Hbv Reactivation ◽  
Virus Reactivation ◽  
Hepatitis B Virus Reactivation ◽  
B Virus

Abstract Abstract 1944 Poster Board I-967 Reactivation of hepatitis B virus (HBV) infection in patients receiving chemotherapy, immunosuppressive therapy, and organ transplantation is well-recognized complication in patients with HBsAg positive patients. Although, prophylaxis with anti-viral drug is proposed for HBV surface antigen (HBsAg) positive patients and is considered as a standard managements, the risk of developing HBV reactivation and optimal therapy in HBsAg negative but anti-HBV core antigen (anti-HBc) positive patients remained to be elucidated. In addition the use of rituximab has been reported to cause even fatal HBV related hepatic failure in these patients. We retrospectively investigated the occurrence of HBV reactivation after rituximab containing chemotherapy in HBsAg negative 261 consecutive patients with CD20 positive B-cell lymphoma who admitted Kameda General Hospital over past 5 years. Prior to September 2006, anti-HBc and antibody to HBsAg (anti-HBs) were performed at the discretion of the treating physician. After October 2006, anti-HBc and anti-HBs tests were performed for all patients. HBV reactivation was defined by the seroconversion from HBsAg negative to positive with or without an increase of HBV-DNA from base line levels (>2.6 log copies/ml). Hepatitis attributable to reactivation was defined as a serum alanine aminotransferase (ALT) level greater than 3 folds above the normal upper limit of 2 consecutive determinations more than 5 days apart without feature of hepatitis A, hepatitis C or other causes. Lymphoma subtypes were diffuse large B cell lymphoma (DLBCL; 162 cases, 61%), follicular lymphoma (FL; 58 cases, 22%), mantle cell lymphoma (MCL; 11 cases, 4%), Burkitt lymphoma (BL; 6 cases, 2%), chronic lymphocytic leukemia (CLL; 6 cases, 2%), and other B cell lymphomas (18 cases, 7%) and various courses and treatments containing rituximab were performed such as CHOP, ESHAP, hyper-CVAD etc. Among the 261 patients, the prevalence of HBsAg positive is 9 (3.4%) and all of them were successfully treated by rituximab containing regimens and concurrent use of antiviral agents without development of severe hepatitis. Twenty-two patients were not tested both anti-HBc and anti-HBs before rituximab administration. Therefore, 230 patients were tested both HBsAg and anti-HBc before treatment. Fifty-six of 230 patients (24.3%) were isolated anti-HBc positive and the rest of 174 patients were anti-HBc negative. Anti-HBc IgM was tested in 29 of 56 anti-HBc positive patients and all of the 29 patients were negative for anti-HBc IgM. Anti-HBs was positive in 5/174 patients (2.8%) and 36/56 patients (65.4%) in anti-HBc negative patients and positive patients, respectively. Among 56 patients with positive anti-HBc, 5 patients (13.9%) became HBsAg positive after rituximab containing therapy, while none of 174 patients with negative anti-HBc became positive for HBsAg with median follow up of 24 months. Among 5 patients with HBV reactivation, 4 patients were isolated anti-HBc and one patient who received allogeneic stem cell transplantation was both anti-HBs and anti-HBc positive before the start of rituximab, although his anti-HBs decline and disappeared after transplantation with the use of prednisone for chronic GVHD. All of the 5 patients received entecavir on detection of HBsAg and showed prompt decrease of HBV-DNA, however, 4 of 5 patients exhibited mild to moderate elevation of ALT. None of them developed fulminant hepatic failure. We conclude that patients with isolated anti-HBc are at high risk for HBV reactivation (p=0.011, by Fisher's exact test) and should be monitored closely for HBsAg, anti-HBs, HBV-DNA, transaminase levels during and after rituximab containing treatment. Although preemptive use of entecavir from detection of HBsAg or HBV-DNA enabled us to manage hepatitis B virus reactivation and liver injury successfully, mild to moderate hepatic flare could not prevented in our patients. Therefore, these approaches should be further evaluated in the context of clinical usefulness, safety, cost-effectiveness. Disclosures: No relevant conflicts of interest to declare.

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

2014 ◽  
Vol 32 (33) ◽  
pp. 3736-3743 ◽  
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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