Average corticosteroid dose and risk for HBV reactivation and hepatitis flare in patients with resolved hepatitis B infection

ObjectivesCorticosteroids remain the mainstay of treatment for rheumatic diseases but can cause hepatitis B virus (HBV) reactivation in patients with resolved HBV infection. Risk assessment and stratification are needed to guide the management of these patients before corticosteroid therapy.MethodsWe prospectively enrolled patients with negative hepatitis B surface antigen positive Anti-hepatitis B core status with or without corticosteroid use and determined corticosteroid exposure by calculating cumulative dose and time-weighted average daily dose of prednisone. The primary outcome was the time to a composite of HBV reactivation, hepatitis flare or severe hepatitis.ResultsAmong 1303 participants, the median of cumulative dose and time-weighted average dose of prednisone used in this cohort was 3000 mg (IQR: 300–6750 mg) and 15 mg/day (IQR: 10–20 mg/day), respectively. In multivariable analyses, cumulative dose showed inverted V-shaped relationship with primary events, which peaked at a cumulative dose of 1506 mg (HR: 3.72; 95% CI, 1.96 to 7.08). Quartiles of time-weighted average dose were independently associated with a monotonic increase in event risk (HR per quartile increase: 2.15; 95% CI, 1.56 to 2.98), reaching an HR of 49.48 (95% CI, 6.24 to 392.48) in the top quartile. The incidence of primary outcome was 16.67 per 100 person-years in the top quartile of time-weighted average dose (Q4>20 mg/day). Other quartiles all had an incidence of primary outcome less than 10 per 100 person-years.ConclusionPatients with time-weighted average prednisone dose greater than 20 mg/day would be classified as the high risk for HBV reactivation or hepatitis flare. Prophylactic Anti-HBV therapy may be needed for these high-risk patients.Trial registration numberChiCTR1900023955.

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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 ◽

10.7717/peerj.7481 ◽

2019 ◽

Vol 7 ◽

pp. e7481 ◽

Cited By ~ 5

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.

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Hepatitis B Virus Screening Before Chemotherapy for Lymphoma: A Cost-Effectiveness Analysis

Journal of Clinical Oncology ◽

10.1200/jco.2011.40.7510 ◽

2012 ◽

Vol 30 (26) ◽

pp. 3167-3173 ◽

Cited By ~ 77

Author(s):

Urszula Zurawska ◽

Lisa K. Hicks ◽

Gloria Woo ◽

Chaim M. Bell ◽

Murray Krahn ◽

...

Keyword(s):

Cost Effectiveness ◽

Hepatitis B Virus ◽

High Risk ◽

Hepatitis B ◽

Antiviral Therapy ◽

Hepatitis B Surface Antigen ◽

Third Party ◽

Hbv Reactivation ◽

B Virus ◽

Hbv Screening

Purpose Hepatitis B virus (HBV) reactivation is a potentially fatal complication of chemotherapy that can be largely prevented with antiviral prophylaxis. It remains unclear whether HBV screening is cost effective. Methods A decision model was developed to compare the clinical outcomes, costs, and cost effectiveness of three HBV screening strategies for patients with lymphoma before R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy: screen all patients for hepatitis B surface antigen (HBsAg; Screen-All), screen patients identified as being at high risk for HBV infection (Screen-HR), and screen no one (Screen-None). Patients testing positive were administered antiviral therapy until 6 months after completion of chemotherapy. Those not screened were initiated on antiviral therapy only if HBV hepatitis occurred. Probabilities of HBV and lymphoma outcomes were derived from systematic literature review. A third-party payer perspective was adopted, costs were expressed in 2011 Canadian dollars, and a 1-year time horizon was used. Results Screen-All was the dominant strategy. It was least costly at $32,589, compared with $32,598 for Screen-HR and $32,657 for Screen-None. It was also associated with the highest 1-year survival rate at 84.99%, compared with 84.96% for Screen-HR and 84.86% for Screen-None. The analysis was sensitive to the prevalence of HBsAg positivity in the low-risk population, with Screen-HR becoming least costly when this value was ≤ 0.20%. Conclusion In patients receiving R-CHOP for lymphoma, screening all patients for HBV reduces the rate of HBV reactivation (10-fold) and is less costly than screening only high-risk patients or screening no patients.

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Hepatitis B Virus Screening and Management for Patients With Cancer Prior to Therapy: ASCO Provisional Clinical Opinion Update

Journal of Clinical Oncology ◽

10.1200/jco.20.01757 ◽

2020 ◽

Vol 38 (31) ◽

pp. 3698-3715 ◽

Cited By ~ 2

Author(s):

Jessica P. Hwang ◽

Jordan J. Feld ◽

Sarah P. Hammond ◽

Su H. Wang ◽

Devena E. Alston-Johnson ◽

...

Keyword(s):

Hepatitis B Virus ◽

High Risk ◽

Hepatitis B ◽

Antiviral Therapy ◽

Hormonal Therapy ◽

Hepatitis B Surface Antigen ◽

Anticancer Therapy ◽

Hbv Reactivation ◽

B Virus ◽

Chronic Hbv

PURPOSE This Provisional Clinical Opinion update presents a clinically pragmatic approach to hepatitis B virus (HBV) screening and management. PROVISIONAL CLINICAL OPINION All patients anticipating systemic anticancer therapy should be tested for HBV by 3 tests—hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) total immunoglobulin (Ig) or IgG, and antibody to hepatitis B surface antigen—but anticancer therapy should not be delayed. Findings of chronic HBV (HBsAg-positive) or past HBV (HBsAg-negative and anti-HBc–positive) infection require HBV reactivation risk assessment. Patients with chronic HBV receiving any systemic anticancer therapy should receive antiviral prophylactic therapy through and for minimum 12 months following anticancer therapy. Hormonal therapy alone should not pose a substantial risk of HBV reactivation in patients with chronic HBV receiving hormonal therapy alone; these patients may follow noncancer HBV monitoring and treatment guidance. Coordination of care with a clinician experienced in HBV management is recommended for patients with chronic HBV to determine HBV monitoring and long-term antiviral therapy after completion of anticancer therapy. Patients with past HBV infection undergoing anticancer therapies associated with a high risk of HBV reactivation, such as anti-CD20 monoclonal antibodies or stem-cell transplantation, should receive antiviral prophylaxis during and for minimum 12 months after anticancer therapy completion, with individualized management thereafter. Careful monitoring may be an alternative if patients and providers can adhere to frequent, consistent follow-up so antiviral therapy may begin at the earliest sign of reactivation. Patients with past HBV undergoing other systemic anticancer therapies not clearly associated with a high risk of HBV reactivation should be monitored with HBsAg and alanine aminotransferase during cancer treatment; antiviral therapy should commence if HBV reactivation occurs. Additional information is available at www.asco.org/supportive-care-guidelines .

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α-Fetoprotein level-dependent early hepatitis B surface antigen decline during entecavir therapy in chronic hepatitis B with hepatitis flare

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkw019 ◽

2016 ◽

Vol 71 (6) ◽

pp. 1601-1608 ◽

Cited By ~ 10

Author(s):

Wen-Juei Jeng ◽

Yi-Cheng Chen ◽

Ming-Ling Chang ◽

Yun-Fan Liaw

Keyword(s):

Chronic Hepatitis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Surface Antigen ◽

Hepatitis B Surface Antigen ◽

Hepatitis Flare

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Hepatitis B Awareness Among Medical Students And Their Vaccination Status In A Medical College In Western UP.

10.36106/ijsr/0601604 ◽

2019 ◽

pp. 57-59

Author(s):

Rajni Dawar ◽

Tabassum Yasmin ◽

Ajay Kumar Jha

Keyword(s):

Medical Students ◽

High Risk ◽

Data Collection ◽

Hepatitis B ◽

Health Care Professionals ◽

Hepatitis B Surface Antigen ◽

Vaccination Status ◽

Hepatitis B Vaccination ◽

Universal Precautions ◽

Medical College

Background: India is in the intermediate hepatitis B virus endemicity zone with hepatitis B surface antigen prevalence among the general population ranging from 2% to 8%.Health care professionals are at a high risk of getting .Hep B infection which can be prevented by strategies like vaccination, increasing awareness and following universal precautions. The present study was conducted on medical students (3rd Semester) to evaluate their knowledge regarding HBV and to know their vaccination status. Also along with data collection, students were educated about hepatitis B vaccine and about universal precautions before they start with their clinical postings. Methods: Cross sectional study was carried out on 3rd semester MBBS students (batch 2012-2013). All the students present on the day of data collection were included in the study and interviewed using pretested questionnaire. Data was analyzed using percentages. Results: Most of the students had good knowledge about disease and modes of transmission & prevention. Surprisingly only 56.6 percent were aware of high risk of transmission to health professional and doctors. Main source of information was media (85.4percent).Nearly 82% of the students were immunized and main reason among those unimmunized was unawareness about vaccine availability. Conclusions: It is recommended that Hepatitis B vaccination should be made available for all unimmunized students who enter medical profession. The orientation and sensitization programm should be held to create awareness regarding HBV infection preferably at the time of admission into medical college ,else no later than start of their clinical posting.

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

Journal of Clinical Oncology ◽

10.1200/jco.2012.48.5938 ◽

2013 ◽

Vol 31 (22) ◽

pp. 2765-2772 ◽

Cited By ~ 202

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.

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Hepatitis B Reactivation in the Treatment of Non-Hodgkin Lymphoma

Cancer Control ◽

10.1177/1073274818767879 ◽

2018 ◽

Vol 25 (1) ◽

pp. 107327481876787

Author(s):

Matthew Kelling ◽

Lubomir Sokol ◽

Samir Dalia

Keyword(s):

Cancer Therapy ◽

Hepatitis B ◽

Hodgkin Lymphoma ◽

Hepatitis B Surface Antigen ◽

Liver Function Tests ◽

Hbv Dna ◽

Hbv Reactivation ◽

Hepatitis B Infection ◽

Serological Testing ◽

Non Hodgkin Lymphoma

Chronic active hepatitis B infection (HBV) has been implicated in lymphomagenesis of non-Hodgkin lymphoma (NHL). Treatment of cancer including NHL with chemotherapy or immunotherapy can lead to HBV reactivation in previously infected patients. Serological testing of HBV prior to initiation of this therapy is recommended by several national and international medical agencies and expert panels. Patients with positive hepatitis B surface antigen (HBsAg) and anti-hepatitis B core antibody (anti-HBc ab) need to start antiviral therapy with entecavir or tenofovir prior to initiation of chemotherapy or immunotherapy and continue this treatment for 6 to 12 months after completion of cancer therapy to avoid late HBV reactivation. Monitoring of HBV DNA viral load and liver function tests should be done during cancer therapy in infected patients. Hepatitis B infection vaccination resulted in decreases prevalence of HBV virus carriers and decreased incidence of virus-induced malignancies.

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