Outcomes and risk factors for hepatitis B virus (HBV) reactivation after kidney transplantation in occult HBV carriers

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.

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Effect of national recommendations on hepatitis B virus screening in a large U.S. cancer center.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.34_suppl.175 ◽

2012 ◽

Vol 30 (34_suppl) ◽

pp. 175-175

Author(s):

Jessica Hwang ◽

Michael Fisch ◽

Anna Lok ◽

Hong Zhang ◽

John Vierling ◽

...

Keyword(s):

Risk Factors ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Solid Tumors ◽

Cancer Center ◽

Hbv Reactivation ◽

Entire Study Period ◽

Entire Study ◽

B Virus ◽

Hbv Screening

175 Background: National organizations recommend screening for hepatitis B virus (HBV) before chemotherapy but differ regarding which patients should be screened. We aimed to determine changes in screening rates at a cancer center after national recommendations were published between 2008 and 2010. Methods: We conducted a retrospective cohort study of HBV screening in cancer patients registered 1/2004 through 4/2011. Screening was defined as HBsAg and anti-HBc tests ordered around initial chemotherapy. We compared screening rates for 3 periods: before publication recommendations, during the period of publication of CDC, NCCN, AASLD, IOM, and ASCO recommendations, and after publication of recommendations. Logistic regression models were used to identify predictors of screening. Results: Of 139,981 new patients, 18,688 received chemotherapy, and 3,020 (16.2%) were screened. HBV screening rates increased over the 3 periods (14.8%, 18.2%, 19.9%; p<0.0001), but <19% of patients with HBV risk factors were screened. Among patients with hematologic malignancies, over 66% were screened during the entire study period, and odds of screening nearly doubled after publication of recommendations (p<0.0001). Less than 4% of patients with solid tumors were screened during the entire study period despite 70% increase in odds of screening after recommendations (p=0.003). Other predictors of screening included younger age, planned rituximab therapy, and known risk factors for HBV infection. Conclusions: HBV screening increased after publication of national recommendations, yet most patients with solid tumors or HBV risk factors remained unscreened. Efforts are needed to increase awareness of the importance of HBV screening prior to chemotherapy and antiviral prophylaxis to prevent HBV reactivation.

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

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2016-209973 ◽

2016 ◽

Vol 76 (6) ◽

pp. 1051-1056 ◽

Cited By ~ 42

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.

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Treatment or Prophylaxis against Hepatitis B Virus Infection in Patients with Rheumatic Disease Undergoing Immunosuppressive Therapy: An Update

Journal of Clinical Medicine ◽

10.3390/jcm10122564 ◽

2021 ◽

Vol 10 (12) ◽

pp. 2564

Author(s):

Cristina Stasi ◽

Giacomo Tiengo ◽

Sinan Sadalla ◽

Anna Linda Zignego

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Immunosuppressive Therapy ◽

Antiviral Treatment ◽

Hbv Infection ◽

Hbv Reactivation ◽

Close Monitoring ◽

Occult Hbv ◽

Chronic Hepatitis B Virus ◽

B Virus

Chronic hepatitis B virus (HBV) flares or reactivations are serious causes of morbidity or mortality in rheumatologic patients undergoing immunosuppressive therapy. The recent insights in the pathogenesis of rheumatic diseases led to the use of new immunosuppressive therapies indicated in case of failure, partial response, or intolerance of conventional synthetic disease-modifying anti-rheumatic drugs. Based on these premises, this review examines and discusses the main rheumatologic treatments that could require the initiation of prophylactic treatment or close monitoring of occult HBV infection in patients beginning antiviral therapy at the first signs of HBV reactivation, or antiviral treatment in chronic HBV-infected patients. We searched for relevant studies published in the last five years. Studies suggested that the presence of HBV infection is common in rheumatic patients and HBV reactivation during these immunosuppressant treatments is quite frequent in these kinds of patients. Therefore, before starting an immunosuppressive therapy, patients should be screened for HBsAg, anti-HBs, and anti-HBc and, on the basis of markers positivity, they should be carefully characterized for HBV infection phases. In conclusion, screening of HBV infection in patients undergoing immunosuppressive therapy with subsequent HBV monitoring, prophylaxis or treatment consistently reduces the risk of clinical consequences.

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Hepatitis B virus reactivation: overview and management

Future Virology ◽

10.2217/fvl-2021-0275 ◽

2021 ◽

Author(s):

Wei Huang ◽

Lingyao Du ◽

Hong Tang

Keyword(s):

Risk Factors ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Immunosuppressive Treatment ◽

Host Factors ◽

Hbv Reactivation ◽

Virus Reactivation ◽

Early Prevention ◽

Circular Dna ◽

B Virus

Hepatitis B virus (HBV) can hide in the liver in the form of covalently closed circular DNA. When the body’s immunity changes, HBV reactivation (HBV-R) can occur. The risk of HBV-R is determined by the complex interaction among virological factors, medication factors and host factors. However, many patients do not know that they are infected with HBV, and doctors often do not invest enough time to systematically evaluate the patient’s HBV-R risk factors before immunosuppressive treatment. Therefore, HBV clinical screening should be vigorously promoted to achieve early detection and early prevention for patients with high risk of HBV-R. The mechanism, clinical features, risk factors, HBV-R under different disease etiologies, prevention and treatment of HBV-R were summarized to improve the in-depth understanding and awareness.

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Durability of Antibody Response Against the Hepatitis B Virus in Kidney Transplant Recipients: A Proposed Immunization Guideline From a 3-Year Follow-up Clinical Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy342 ◽

2018 ◽

Vol 6 (1) ◽

Cited By ~ 1

Author(s):

Wiwat Chancharoenthana ◽

Asada Leelahavanichkul ◽

Suwasin Udomkarnjananun ◽

Salin Wattanatorn ◽

Yingyos Avihingsanon ◽

...

Keyword(s):

Kidney Transplantation ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Booster Dose ◽

Hepatitis B Surface Antigen ◽

Hbv Reactivation ◽

Kidney Transplant Recipients ◽

Hbv Vaccination ◽

B Virus

Abstract Background Despite the importance of hepatitis B virus (HBV) immunization in kidney transplantation (KT), data are lacking on fluctuations in hepatitis B surface antibody (anti-HBsAb) levels and optimal levels for KT recipients. Methods The study consisted of anti-HBsAb-positive recipients aged 18–70 years at the time of the KT. Recipients with anti-HBsAb <100 IU/L received a single booster HBV vaccination, and anti-HBsAb was measured at baseline and 3, 6, 12, 18, and 24 months post-KT. Anti-HBsAb, quantitative HBV deoxyribonucleic acid testing (12 and 24 months post-KT), and hepatitis B core-related antigen (24 months post-KT) were evaluated in recipients with anti-HBsAb >100 IU/L who received a hepatitis B surface antigen positive renal allograft. Results Seventy-six of 257 (29.6%) KT recipients with anti-HBsAb <100 IU/L at the time of enrollment received a single booster of HBV vaccination. Anti-HBsAb levels increased (≥100 IU/L) 1 and 3 months post-booster dose in 86% and 93% of cases, respectively. Anti-HBsAb levels were ≥100 IU/L in 95% of these recipients 6 months post-booster dose. Among 181 (70%) recipients with anti-HBsAb ≥100 IU/L without a booster dose, anti-HBsAb gradually decreased after the KT from 588 IU/L at baseline to 440 and 382 IU/L 3 and 6 months post-KT, respectively (P < .01). Conclusions To ensure optimal immunity against HBV, KT recipients should first be stratified according to their risk of HBV reactivation. Kidney transplantation recipients of renal allografts from HBV nonviremic or viremic donors should be reimmunized when their anti-HBsAb titers are <250 IU/L. A cutoff level of 100 IU/L is recommended in other cases.

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Clinical Prediction of Failure of Lamivudine Prophylaxis for Hepatitis B Virus-Infected Patients Undergoing Cytotoxic Chemotherapy for Malignancy

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00821-12 ◽

2012 ◽

Vol 56 (11) ◽

pp. 5511-5519 ◽

Cited By ~ 10

Author(s):

In Kyoung Kim ◽

Byeong Gwan Kim ◽

Won Kim ◽

Donghee Kim ◽

Yoon Jun Kim ◽

...

Keyword(s):

Risk Factors ◽

Liver Cirrhosis ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Distant Metastasis ◽

Hbv Dna ◽

Hbv Reactivation ◽

High Baseline ◽

Virologic Breakthrough ◽

B Virus

ABSTRACTAlthough lamivudine (LAM) prophylaxis is recommended for patients infected with hepatitis B virus (HBV) undergoing chemotherapy for malignant disease, HBV reactivation sometimes occurs during or after LAM administration. The aim of this study was to determine predictors of LAM prophylactic failure in patients with malignancies. Patients with malignancies were routinely screened for serum hepatitis B surface antigen (HBsAg) from June 2002 to August 2008. All consecutive, HBsAg-positive patients received LAM prophylaxis during and after completion of chemotherapy. We assessed risk factors for virologic breakthrough and withdrawal hepatitis. Death without HBV reactivation was regarded as a competing risk event, which was adjusted by Fine and Gray's model. A total of 110 patients were included in this study. They received LAM prophylaxis for a median of 9.2 months. Virologic breakthrough occurred in 15 patients at a median of 10.9 months from the initiation of LAM prophylaxis. Withdrawal hepatitis occurred in 15 patients at a median of 2.4 months after cessation of LAM prophylaxis. Multivariable analysis showed that high baseline HBV DNA titer (≥2,000 IU/ml) (hazard ratio [HR], 9.94;P= 0.0063) and the use of rituximab (HR, 3.19;P= 0.027) were significant predictors of virologic breakthrough and that high baseline HBV DNA titer (HR, 5.90;P= 0.007), liver cirrhosis (HR, 10.4;P= 0.002), and distant metastasis (HR, 5.14;P= 0.008) were independent risk factors for withdrawal hepatitis. Patients with high viremia, liver cirrhosis, rituximab treatment, and distant metastasis are at high risk of prophylactic failure and need antiviral agents with a greater barrier to resistance.

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Hepatitis B Virus (HBV) Reactivation Following Pharmacological Eradication of Hepatitis C Virus (HCV)

Viruses ◽

10.3390/v11090850 ◽

2019 ◽

Vol 11 (9) ◽

pp. 850 ◽

Cited By ~ 1

Author(s):

Mariantonietta Pisaturo ◽

Margherita Macera ◽

Loredana Alessio ◽

Federica Calò ◽

Nicola Coppola

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Hbv Infection ◽

Clinical Event ◽

Hbv Reactivation ◽

Occult Hbv Infection ◽

Occult Hbv ◽

B Virus

The US Food and Drug Administration issued a black box warning related to the risk of reactivation of overt/occult hepatitis B virus (HBV) infection during direct acting-antivirals (DAA) treatment. This review evaluated the prevalence of HBV reactivation after hepatitis C virus (HCV) pharmacological suppression and hypothesized the management and prevention of this reactivation. During and after DAA-based treatment, reactivation of HBV infection is common in patients with detectable serum HBsAg (from 2% to 57%) and very low (less than 3%) in individuals with isolated anti-HBc antibodies. The severity of hepatic damage may range from HBV reactivation without hepatitis to fulminant hepatic failure requiring liver transplantation. Thus, HBsAg-positive patients should receive nucleo(s)tide analog (NA) treatment or prophylaxis at the same time as DAA therapy. For those patients with occult B infection, there are no sufficient recommendations to start prophylactic treatment. Reactivation of overt or occult HBV infection during or after eradication of HCV infection is an issue to consider, and additional studies would help to determine the best management of this virological and clinical event.

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The Study of Hepatitis B Virus Reactivation

Infection International ◽

10.1515/ii-2017-0095 ◽

2014 ◽

Vol 3 (4) ◽

pp. 187-192

Author(s):

Zhao-chun Chi

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Antiviral Therapy ◽

Endemic Area ◽

Hbv Dna ◽

Hbv Reactivation ◽

Virus Reactivation ◽

Occult Hbv ◽

B Virus ◽

Suppression Of Immune Response

Abstract Hepatitis B virus (HBV) reactivation after chemotherapy or immunosuppressive therapy is a cause of liver-related morbidity and mortality. Not all chronic hepatitis B patients will lead to HBV reactivation. The incidence is 0.3%- 30.2% according to the reports. The mechanism of HBV reactivation is still unclear, but it is believed that the viral load is increasing due to the suppression of immune response. No uniform diagnostic criteria are available. HBV reactivation can be confirmed by an increase of serum HBV DNA level. Recently, awareness of reactivation of occult HBV has been improved, especially in HBV endemic area. Preemptive antiviral therapy was the best approach to prevent the HBV reactivation. HBV reactivation can lead to acute hepatitis, severe hepatitis and acute liver failure. Therefore, it is worthy of great attention and further study. Antiviral therapy is safe and effective to prevent HBV reactivation.

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

Blood ◽

10.1182/blood.v114.22.4794.4794 ◽

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.

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