Risk of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen negative/hepatitis B core antibody positive patients receiving rituximab-containing combination chemotherapy without routine antiviral prophylaxis

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.

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

The Journal of Rheumatology ◽

10.3899/jrheum.110289 ◽

2011 ◽

Vol 38 (10) ◽

pp. 2209-2214 ◽

Cited By ~ 32

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.

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Hepatitis B Virus Screening and Real Life Data in Patients with Solid Tumor Receiving Chemotherapy

Archives of Iranian Medicine ◽

10.34172/aim.2020.111 ◽

2020 ◽

Vol 23 (12) ◽

pp. 835-841

Author(s):

Sami Fidan ◽

Evren Fidan ◽

Celal Alandağ ◽

Murat Erkut ◽

Arif Mansur Cosar

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Hepatitis B Surface Antigen ◽

Real Life ◽

Solid Cancer ◽

Hbv Reactivation ◽

Antiviral Prophylaxis ◽

Real Life Data ◽

B Virus ◽

Hbv Screening

Background: Reactivation of the hepatitis B virus (HBV) either during or after chemotherapy may cause serious and sometimes fatal hepatitis. All patients undergoing chemotherapy should therefore be screened in terms of HBV before chemotherapy. The purpose of this research was to identify HBV screening rates in patients with solid cancer undergoing parenteral chemotherapy and to determine the outcomes of patients undergoing HBV screening. Methods: Data for patients undergoing parenteral chemotherapy for solid cancer from January 1, 2012 to December 30, 2018 were retrieved from our electronic health record patient files in this retrospective study. Screening was defined as hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb) tests carried out within six months prior the first chemotherapy session. Results: Four thousand fifty-eight (63%) of the 6440 patients who underwent parenteral chemotherapy were screened for HBsAg and/or HBcAb. The proportions of patients screened for HBsAg and HBcAb improved from 38.8% (2012) to 76.3% (2018), and from 0.2% (2012) to 43% (2018), respectively (P<0.001). The HBsAg and HBcAb positivity rates were 2.9% and 36.5%, respectively. Antiviral prophylaxis was started in 11.8% of HBsAg-negative/HBcAb-positive patients and 40.5% of HBsAg-positive patients. HBV reactivation did not occur in patients receiving antiviral prophylaxis, but was identified in 7.2% of HBsAg-positive patients and 0.6% of HBsAg-negative/HBcAb-positive patients without antiviral prophylaxis. Conclusion: Although HBV screening rates before chemotherapy are increasing among solid cancer patients, the rate of initiation of antiviral prophylaxis is still low. It is therefore important to raise awareness regarding HBV reactivation during/after chemotherapy.

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

Blood ◽

10.1182/blood.v124.21.1196.1196 ◽

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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