scholarly journals Rituximab increases the risk of hepatitis B virus reactivation in non-Hodgkin lymphoma patients who are hepatitis B surface antigen-positive or have resolved hepatitis B virus infection in a real-world setting: a retrospective study

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7481 ◽  
Author(s):  
Yu-Fen Tsai ◽  
Ching-I Yang ◽  
Jeng-Shiun Du ◽  
Ming-Hui Lin ◽  
Shih-Hao Tang ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hodgkin Lymphoma ◽  
Hepatitis B Surface Antigen ◽  
Hbv Infection ◽  
Hbv Reactivation ◽  
Virus Reactivation ◽  
Non Hodgkin Lymphoma ◽  
B Virus ◽  
Hepatitis Flare

Background Hepatitis B virus (HBV) reactivation with a hepatitis flare is a common complication in lymphoma patients treated with immunotherapy and/or chemotherapy. Anti-HBV prophylaxis is suggested for non-Hodgkin lymphoma (NHL) patients undergoing rituximab therapy, even those with resolved HBV infection. Since anti-HBV prophylaxis for patients with resolved HBV infection is not covered by national health insurance in Taiwan, a proportion of these patients receive no prophylaxis. In addition, late HBV reactivation has emerged as a new issue in recent reports, and no consensus has been reached for the optimal duration of antiviral prophylaxis. Thus, the aim of our study was to investigate the incidence and outcomes of HBV reactivation in NHL patients in a real-world setting and to study the frequency of late HBV reactivation. Materials Non-Hodgkin lymphoma patients who received rituximab and/or chemotherapy at our institute between January 2011 and December 2015 and who were hepatitis B surface antigen (HBsAg)- or hepatitis B core antibody (HBcAb)-positive were reviewed retrospectively. Results A total of 388 patients were screened between January 2011 and December 2015. In total, 196 patients were excluded because HBsAg was not assessed, HBcAb was negative or not assessed, or they were not treated with immunosuppressive therapy. Finally, the retrospective study included 62 HBsAg-positive NHL patients and 130 NHL patients with resolved HBV infection (HBsAg-negative and HBcAb-positive). During a median 30.5-month follow-up period, seven patients experienced HBV reactivation, five of whom had a hepatitis flare. The incidence of HBV reactivation did not significantly differ between the HBsAg-positive patients and the resolved HBV infection population without anti-HBV prophylaxis (4.8% vs. 3.1%, P = 0.683). All patients with HBV reactivation were exposed to rituximab. Notably, late HBV reactivation was not uncommon (two of seven patients with HBV reactivation events, 28.6%). Hepatitis B virus reactivation did not influence the patients’ overall survival. An age ≥65 years and an advanced disease stage were independent risk factors for poorer overall survival. Conclusion The incidence of HBV reactivation was similar between the HBsAg-positive patients with antiviral prophylaxis and the resolved HBV infection population without anti-HBV prophylaxis. All HBV reactivation events occurred in NHL patients exposed to rituximab. Late reactivation was not uncommon. The duration of regular liver function monitoring for more than 1 year after immunosuppressive therapy or after withdrawal of prophylactic antiviral therapy should be prolonged. Determining the exact optimal duration of anti-HBV prophylaxis is warranted in a future prospective study for NHL patients treated with rituximab-containing therapy.

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.

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.

scholarly journals Why, When, and How to Prevent Hepatitis B Virus Reactivation in Cancer Patients Undergoing Chemotherapy

2011 ◽  
Vol 9 (5) ◽  
pp. 465-477 ◽  
Author(s):  
Bhumsuk Keam ◽  
Jeong-Hoon Lee ◽  
Seock-Ah Im ◽  
Jung-Hwan Yoon
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Clinical Problem ◽  
Hbv Reactivation ◽  
Virus Reactivation ◽  
Hbv Replication ◽  
B Virus ◽  
Prophylactic Antiviral Therapy ◽  
Meta Analyses

Hepatitis B virus (HBV) reactivation is a serious clinical problem in HBV carriers undergoing chemotherapy. The clinical course of HBV reactivation can be separated into 2 phases: 1) an increase in HBV replication and 2) hepatic injury. Patients with resolved HBV infections (negative for hepatitis B surface antigen [HBsAg], and positive for both hepatitis B core antibody [anti-HBc] and/or hepatitis B surface antibody) can experience HBV reactivation, and Western guidelines recommend that not only HBsAg but also anti-HBc be screened before initiation of chemotherapy or immunosuppressive therapy. Several meta-analyses have repeatedly confirmed the prophylactic role of lamivudine in preventing HBV reactivation. In conclusion, screening for HBV is required before chemotherapy, and prophylactic antiviral therapy can reduce not only the incidence of HBV reactivation but also HBV-related morbidity and mortality.

Risk of hepatitis B virus (HBV) reactivation in non-Hodgkin lymphoma patients receiving rituximab-chemotherapy: A meta-analysis

2013 ◽  
Vol 57 (3) ◽  
pp. 209-214 ◽  
Author(s):  
Hua-Jie Dong ◽  
Ling-Na Ni ◽  
Gui-Feng Sheng ◽  
Hong-Lei Song ◽  
Jian-Zhong Xu ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hodgkin Lymphoma ◽  
Meta Analysis ◽  
Hbv Reactivation ◽  
Non Hodgkin Lymphoma ◽  
B Virus

scholarly journals Incidence of hepatitis B virus reactivation in patients with resolved infection on immunosuppressive therapy for rheumatic disease: a multicentre, prospective, observational study in Japan

2016 ◽  
Vol 76 (6) ◽  
pp. 1051-1056 ◽  
Author(s):  
Wataru Fukuda ◽  
Tadamasa Hanyu ◽  
Masaki Katayama ◽  
Shinichi Mizuki ◽  
Akitomo Okada ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Rheumatic Disease ◽  
Hbv Dna ◽  
Hbv Infection ◽  
Hbv Reactivation ◽  
Virus Reactivation ◽  
Virus Surface ◽  
B Virus

BackgroundAlthough the reactivation of hepatitis B virus (HBV) is recognised as a serious complication in patients with rheumatic disease (RD) receiving immunosuppressive drugs (ISDs), the incidence and risk factors for reactivation remain controversial.ObjectivesTo investigate the incidence and risk factors for HBV reactivation in patients with RD.MethodsWe performed a multicentre, observational, prospective study over 2 years in patients with resolved HBV infection. Patients with RD treated with a dose of ≥5 mg/day prednisolone and/or synthetic or biological ISDs with negative HB virus surface antigen and positive anti-HB virus surface antibody (HBsAb) and/or anti-HB virus core antibody (HBcAb) were enrolled. Quantitative HBV DNA results and related data were regularly recorded.ResultsAmong 1042 patients, including 959 with rheumatoid arthritis, HBV DNA was detected in 35 (1.93/100 person-years), with >2.1 log copies/mL observed in 10 patients (0.55/100 person-years). None of the reactivated patients, including seven treated with a nucleic acid analogue, showed overt hepatitis. Low HBsAb titres and advanced age seemed to be risk factors for HBV reactivation; however, reactivation was observed in three patients with positive HBsAb and negative HBcAb test results. The risk of reactivation was lower with methotrexate but higher with prednisolone among the different types of ISDs. The intervals from the start of ISD to reactivation were relatively long (3–182 months; median, 66 months).ConclusionsThe incidence of HBV reactivation with ISD use was 1.93/100 person-years in patients with RD with resolved HBV infection. No overt hepatitis was observed in the reactivated patients.

scholarly journals Hepatitis B Virus Reactivation Associated With Therapeutic Interventions

2022 ◽  
Vol 8 ◽  
Author(s):  
Young Chang ◽  
Soung Won Jeong ◽  
Jae Young Jang
Keyword(s):  
At Risk ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbv Infection ◽  
Therapeutic Interventions ◽  
Hbv Reactivation ◽  
Solid Organ ◽  
Virus Reactivation ◽  
Populations At Risk ◽  
B Virus

Hepatitis B virus (HBV) reactivation associated with various therapeutic interventions is an important cause of morbidity and mortality in patients with current or resolved HBV infection. Because no curative treatment for HBV infection is yet available, there are many individuals at risk for HBV reactivation in the general population. Populations at risk for HBV reactivation include patients who are currently infected with HBV or who have been exposed to HBV in the past. HBV reactivation and its potential consequences is a concern when these populations are exposed to anti-cancer chemotherapy, immunosuppressive or immunomodulatory therapies for the management of various malignancies, rheumatologic diseases, inflammatory bowel disease, or solid-organ or hematologic stem cell transplantation. Accordingly, it has become important to understand the basics of HBV reactivation and the mechanisms by which certain therapies are more susceptible to HBV reactivation. This review aims to raise the awareness of HBV reactivation and to understand the mechanisms and the risks of HBV reactivation in various clinical settings.

scholarly journals Post-Autotransplant Hepatitis B Virus (HBV) Reactivation in Lymphoma and Multiple Myeloma Patients with Hepatitis B Surface Antigen-Positive or Resolved HBV Infection

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1196-1196
Author(s):  
Jieun Jang ◽  
Hyunsung Park ◽  
Jungyeon Lee ◽  
Yundeok Kim ◽  
Soo Jeong Kim ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
Hbv Infection ◽  
Hbv Reactivation ◽  
B Virus ◽  
Conditioning Regimens ◽  
Anti Cd20

Abstract Background: Although hepatitis B virus (HBV) reactivation in patients with hepatitis B surface antigen (HBsAg)-positive or resolved HBV infection (HBsAg-negative and hepatitis B core antibody [anti-HBc]-positive) undergoing anticancer therapy with or without rituximab has been frequently reported, few studies have evaluated the risk of HBV reactivation in patients receiving autologous stem cell transplantation (ASCT). We studied the rate of hepatitis and HBV reactivation after ASCT in lymphoma and multiple myeloma (MM) patients with HBsAg-positive or resolved HBV infection. Methods & Materials: Medical records of patients who diagnosed with lymphoma or MM and received ASCT between November 2005 and April 2014 in Severance hospital were retrospectively analyzed. HBV status was screened routinely at ASCT and when viral-related hepatitis was suspected after ASCT. Hepatitis was defined as a 3-fold or greater increase in serum alanine transaminase (ALT) that exceeded the reference range (>46 IU/L) or an absolute increase of ALT to more than 100 IU/L. HBV reactivation was defined as elevation of serum HBV-DNA level more than 1 log IU/L from baseline in HBsAg(+) patients. In case of resolved HBV patients, positive conversion of HBsAg (reverse seroconversion) with or without increase of ALT was defined as HBV reactivation. Hepatitis and HBV reactivation occurred before 1 year after ASCT was considered ASCT-related in this study. Result: A total of 297 patients (196 lymphoma and 101 MM) were studied. Median age at diagnosis was 47 years (range 16-64). A male to female ratio was 1.36:1. Most common subtype of lymphoma was diffuse large B-cell lymphoma (DLBCL, n=111). The median duration from diagnosis to ASCT was 475 days (range 105-5230) and 175 days (range 39-5400) in lymphoma and MM patients, respectively. Busulfan-based (n= 161, 82.1%) conditioning regimens were commonly used in lymphoma patients and melphalan-based (n=101, 100%) conditioning regimens were used in MM patients. The patients with HBsAg(-) did not received a routine anti-HBV prophylaxis regardless of the presence of anti-HBc. Nine patients did not tested for HBV at ASCT. Among 274 patients with HBsAg(-), 110 patients were anti-HBc(+) (resolved HBV infection) and 161 patients were anti-HBc(-). Within 1 year after ASCT, 48 of anti-HBc(+) and 71 of anti-HBc(-) patients experienced hepatitis (43.6% vs. 44.1%, p>0.999). The most common cause of hepatitis was drug-related (n= 81, 66.9%). There was no HBsAg reverse seroconversion within 1 year after ASCT. After 1 year, Only one patient with anti-HBc(+) experienced HBV reactivation at days 763 after ASCT and 3 patients with anti-HBc(-) showed HBsAg reverse seroconversion at days 406, 457 and 1172 post-transplant. In the subset of 178 lymphoma patients with HBsAg(-), 90 patients had a history of previous use of anti-CD20 monoclonal antibody, of whom 37 patients were anti-HBc(+). Twelve of anti-HBc(+) and 24 of anti-HBc(-) patients experienced hepatitis (32.4% vs. 45.3%, p=0.276) but there was no HBV reactivation related hepatitis within 1 year after ASCT. Among 14 patients with HBsAg(+) at ASCT, 13 patients received rituximab-containing chemotherapy before ASCT. They had received prophylactic HBV therapy with lamivudine (n=6), telbivudine (n=4), clevudine (n=2), adefovir (n=1) and tenofovir (n=1). Among them, 3 patients with telbivudine (n=1, 25%), clevudine (n=1, 50%) and lamivudine (n=1, 16.7%) experienced HBV reactivation at days 36, 161 and 204 after ASCT. Conclusion: Our data suggest that ASCT-related HBV reactivation is rare in lymphoma and MM patients with resolved HBV infection regardless of previous anti-CD20 therapy. Routine anti-HBV prophylaxis is not necessary for patients with resolved HBV infection. In case of HBsAg(+) patients, antiviral prophylaxis with lamivudine, clevudine, or telbivudine may not be sufficient to prevent HBV reactivation after ASCT. More potent antiviral agents such as adefovir or tenofovir should be considered. Figure 1 Figure 1. Characteristics of 7 patients with HBV reactivation or HBsAg reverse seroconversion after ASCT. Disclosures No relevant conflicts of interest to declare.

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