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.

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.

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

2016 ◽  
Vol 43 (5) ◽  
pp. 869-874 ◽  
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.

Hepatitis B Virus Reactivation by Immunosuppressive Therapy in Patients with Autoimmune Diseases: Risk Analysis in Hepatitis B Surface Antigen-negative Cases

2011 ◽  
Vol 38 (10) ◽  
pp. 2209-2214 ◽  
Author(s):  
MASARU KATO ◽  
TATSUYA ATSUMI ◽  
TAKASHI KURITA ◽  
TOSHIO ODANI ◽  
YUICHIRO FUJIEDA ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Autoimmune Diseases ◽  
Immunosuppressive Therapy ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
Core Antigen ◽  
Hbv Reactivation ◽  
B Virus

Objective.To evaluate the risk of reactivation of resolved hepatitis B virus (HBV) by immunosuppressive therapy in patients with autoimmune diseases.Methods.Thirty-five patients with autoimmune diseases were included in our study; all were hepatitis B surface antigen (HBsAg)-negative and antibody against hepatitis B core antigen-positive. They were followed for 8–124 weeks and clinical outcomes were analyzed, including serum levels of HBV-DNA and aminotransferase every 4 weeks during their immunosuppressive therapy for underlying autoimmune diseases. If HBV-DNA was detected during the immunosuppressive therapy, HBsAg, antibody against HBsAg (anti-HBs), hepatitis B e antigen (HBeAg), and antibody against HBeAg were also monitored every 4 weeks.Results.HBV-DNA was detected in 6 out of 35 patients. Anti-HBs titer was significantly lower in the patients in whom HBV-DNA was detected compared with the others at baseline: 2.83 (range 0.24–168.50) mIU/ml vs 99.94 (range 0.00–5342.98) mIU/ml, respectively (p = 0.036). Outcomes of the 6 patients with HBV reactivation were as follows: HBV-DNA turned negative in 2 patients without nucleic acid analog (NAA) and 1 with NAA; 2 died due to bacterial sepsis; and 1 died due to autoimmune hemolytic anemia. Significant elevation of aminotransferase was found in only 1 patient, but HBsAg converted to positive in 2 patients and HBeAg converted to positive in 1 patient.Conclusion.Reactivation of resolved HBV can occur during standard immunosuppressive therapy for autoimmune diseases. The low titer of baseline anti-HBs may carry its risk.

scholarly journals Screening for and management of hepatitis B virus reactivation in patients treated with anti-B-cell therapy

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 576-583 ◽  
Author(s):  
Shigeru Kusumoto ◽  
Kensei Tobinai
Keyword(s):  
Hepatitis B Virus ◽  
High Risk ◽  
Hepatitis B ◽  
Cell Therapy ◽  
B Cell ◽  
Hbv Dna ◽  
Hbv Infection ◽  
Core Antigen ◽  
Hbv Reactivation ◽  
B Virus

Abstract Reactivation of hepatitis B virus (HBV) is a potentially fatal complication after anti-B-cell therapy. It can develop not only in patients seropositive for hepatitis B surface antigen (HBsAg), but also in those with resolved HBV infection who are seronegative for HBsAg but seropositive for antibodies against hepatitis B core antigen (anti-HBc) and/or antibodies against HBsAg (anti-HBs). The risk of HBV reactivation depends on the balance between replication of the virus and the immune response of the host. Anti-CD20 monoclonal antibody—rituximab in combination with steroid-containing chemotherapy (R-CHOP: rituximab + cyclophosphamide + hydroxydaunorubicin + vincristine + prednisone/prednisolone)—is an important risk factor for HBV reactivation in HBsAg-negative patients. More obviously, HBsAg-positive patients are considered to be at very high risk for HBV reactivation and, in the rituximab era, 59%–80% of these patients develop HBV reactivation after R-CHOP-like chemotherapy. Patients with resolved HBV infection should also be considered at high risk of HBV reactivation, the incidence of which is reported to be 9%–24% in such lymphoma patients. All patients should be screened to identify risk groups for HBV reactivation before initiating anti-B-cell therapy by measuring serum HBV markers including HBsAg, anti-HBc and anti-HBs. To prevent the development of hepatitis due to HBV reactivation after anti-B-cell therapy, antiviral prophylaxis is recommended for HBsAg-positive patients and/or patients in whom HBV DNA is detectable at baseline, whereas regular monitoring of HBV DNA-guided preemptive antiviral therapy is a reasonable and useful approach for patients with resolved HBV infection.

Hepatitis B Virus Reactivation in Malignant Lymphoma with Occult HBV Carrier.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4794-4794
Author(s):  
Noriyasu Fukushima ◽  
Toshihiko Mizuta ◽  
Chisako Urata ◽  
Mariko Tanaka ◽  
Masako Yokoo ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Liver Function ◽  
Malignant Lymphoma ◽  
Prospective Studies ◽  
Hbv Dna ◽  
Core Antigen ◽  
Hbv Reactivation ◽  
Occult Hbv ◽  
B Virus

Abstract Abstract 4794 Background In surface antigen of hepatitis B virus (HBsAg)-positive carrier for anticancer treatment of malignant lymphoma, it is well recognized that reactivation of hepatitis B virus (HBV) occasionally occurs. However, there have been only a few studies of HBV reactivation in serum HBsAg-negative and hepatitis B core antigen (HBcAb)-positive occult HBV carriers. We looked at both retrospective and prospective studies to determine the prevalence, clinical course and risk factor of HBV reactivation during chemotherapy in lymphoma patients. Patients and methods Forty-nine of 128 (38.3%) lymphoma patients were HBsAg negative and HBcAb positive, and 25 of these patients were then given liver function tests and HBsAg tests monthly and serum HBV DNA every 3 months. Results HBV reactivation was observed in two patients (4.0%) who had received intensive chemotherapy including steroid and rituximab. Immediate administration of entecavir therapy after elevation of HBV DNA level was conducted, and this resulted in reduction of it and improvement of liver function test. Conclusions Rituximab plus steroid-containing regimens may increase the risk of HBV reactivation in HBsAgnegative and HBcAb-positive lymphoma patients. More ambitious prospective studies are required to establish clinically useful or cost-effective follow-up methods for control of HBV reactivation in lymphoma patients with occult HBV infection. Disclosures: No relevant conflicts of interest to declare.

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.

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 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.

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.

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