Hepatitis B virus persistence and reactivation

BMJ ◽  
2020 ◽  
pp. m2200
Author(s):  
Yu Shi ◽  
Min Zheng
Keyword(s):  
Immune Response ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Viral Reactivation ◽  
Clinical Settings ◽  
Hbv Reactivation ◽  
Chronic Infections ◽  
Hbv Replication ◽  
B Virus

AbstractHepatitis B virus (HBV) infection causes chronic hepatitis and has long term complications. Individuals ever infected with HBV are at risk of viral reactivation under certain circumstances. This review summarizes studies on HBV persistence and reactivation with a focus on the definitions and mechanisms. Emphasis is placed on the interplay between HBV replication and host immunity as this interplay determines the patterns of persistence following viral acquisition. Chronic infections exhibit as overt persistence when a defective immune response fails to control the viral replication. The HBV genome persists despite an immune response in the form of covalently closed circular DNA (cccDNA) and integrated DNA, rendering an occult state of viral persistence in individuals whose infection appears to have been resolved. We have described HBV reactivation that occurs because of changes in the virus or the immune system. This review aims to raise the awareness of HBV reactivation and to understand how HBV persists, and discusses the risks of HBV reactivation in a variety of clinical settings.

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 Immune-Escape Hepatitis B Virus Mutations Associated with Viral Reactivation upon Immunosuppression

Viruses ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 778 ◽  
Author(s):  
Ivana Lazarevic ◽  
Ana Banko ◽  
Danijela Miljanovic ◽  
Maja Cupic
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Immune Escape ◽  
Major Complication ◽  
Viral Reactivation ◽  
Hbv Reactivation ◽  
Humoral Immune ◽  
B Virus ◽  
History Of ◽  
Gene Variability

Hepatitis B virus (HBV) reactivation occurs as a major complication of immunosuppressive therapy among persons who have recovered from acute hepatitis and those who have controlled chronic infection. Recent literature data emphasize the presence of a high degree of S gene variability in HBV isolates from patients who developed reactivation. In reactivated HBV, the most frequently detected mutations belong to the second loop of “a” determinant in HBsAg. These mutations were identified to be immune escape and responsible for vaccine- and diagnostic-escape phenomena. Their emergence clearly provides survival in the presence of a developed humoral immune response and is often associated with impaired serological diagnosis of HBV reactivation. The knowledge of their existence and roles can elucidate the process of reactivation and strongly highlights the importance of HBV DNA detection in monitoring all patients with a history of HBV infection who are undergoing immunosuppression. This review discusses the possible influence of the most frequently found immune-escape mutations on HBV reactivation.

scholarly journals Roles of Hepatitis B Virus Mutations in the Viral Reactivation after Immunosuppression Therapies

Viruses ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 457 ◽  
Author(s):  
Jun Inoue ◽  
Takuya Nakamura ◽  
Atsushi Masamune
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Immune Escape ◽  
Case Reports ◽  
Hepatitis B Surface Antigen ◽  
Viral Reactivation ◽  
Circular Dna ◽  
Hbv Replication ◽  
B Virus ◽  
Amino Acid Mutations

Reactivation of hepatitis B virus (HBV) is a major problem in patients receiving chemotherapy for malignant diseases or immunosuppression therapies. It has been thought that a reduction in the immune responses might result in the reactivation of HBV replication from covalently closed circular DNA (cccDNA) residing in hepatocytes. However, not only the host’s immune status, but also viral mutations have been reported to be associated with reactivation. Especially, several case reports about amino acid mutations in hepatitis B surface antigen (HBsAg) that escape from immune reactions have been reported, and recent reports showed that the frequencies of such mutations are higher than previously expected. In this review, we summarize the characteristics of viral mutations, including immune escape mutations in HBV-reactivated patients, and discuss their significance.

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.

scholarly journals New Markers in Monitoring the Reactivation of Hepatitis B Virus Infection in Immunocompromised Hosts

Viruses ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 783 ◽  
Author(s):  
Valentina Svicher ◽  
Romina Salpini ◽  
Vincenzo Malagnino ◽  
Lorenzo Piermatteo ◽  
Mohammad Alkhatib ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Immunosuppressive Treatment ◽  
Hbv Infection ◽  
Viral Reactivation ◽  
Hbv Reactivation ◽  
Therapeutic Implications ◽  
B Virus ◽  
New Biomarkers ◽  
Immunocompromised Hosts

Hepatitis B virus (HBV) persistence is at the basis of HBV reactivation as a consequence of chemotherapy and immunosuppressive treatments. The identification of early viral replication indicators and markers of effective HBV immunological control would be useful in monitoring patients who are at risk of potential viral reactivation during the course of immunosuppressive treatment. Currently, international guidelines have shared some criteria to identify patients with a low, medium or high risk of HBV reactivation; however, permanently placing a patient in a definitive category is not always easy. More often, patients move from one category to another during the course of their immunosuppressive treatment; therefore, in many cases, there are no precise indicators or tools for monitoring possible reactivation and establishing the duration and suspension of antiviral prophylaxis. Historically, the sequence of HBV antigens and antibodies and HBV DNA levels has been used to evaluate the different stages of the acute and chronic phases of an HBV infection. In the last few years, new biomarkers, such as anti-HBs and anti-HBc titres, HBV core-related antigen (HBcrAg), ultra-sensitive HBsAg evaluation and HBV RNA, have been used in patients with an HBV infection to evaluate their diagnostic and prognostic potential. The aim of this review is to evaluate the published results on the use of new infection markers in the diagnosis and monitoring of HBV reactivation over the course of immunosuppressive treatments. Moreover, the importance of viral genotypic studies was emphasized, given the diagnostic and therapeutic implications of the mutational profiles of HBsAg during the HBV reactivation phase.

scholarly journals Long-term Immune Response to Hepatitis B Virus Vaccination Regimens in Adults With Human Immunodeficiency Virus 1

2016 ◽  
Vol 176 (5) ◽  
pp. 603 ◽  
Author(s):  
Odile Launay ◽  
Arielle R. Rosenberg ◽  
David Rey ◽  
Noelle Pouget ◽  
Marie-Louise Michel ◽  
...  
Keyword(s):  
Immune Response ◽  
Human Immunodeficiency Virus ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Virus Vaccination ◽  
B Virus ◽  
Immunodeficiency Virus ◽  
Human Immunodeficiency Virus 1

Efficacy and Safety of Long-Term Corticosteroid Monotherapy in 26 Cases of Nephrotic Syndrome with Biopsy-Proven Membranous Nephropathy Induced by Seronegative Hepatitis B Virus-Associated Glomerulonephritis

Nephron ◽  
2021 ◽  
pp. 1-10
Author(s):  
Yan Zhang ◽  
Sha Chen ◽  
Dingping Yang ◽  
Junyun Liu ◽  
Xiaoxiao Zhang ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Membranous Nephropathy ◽  
Efficacy And Safety ◽  
Clinical Trial Registry ◽  
Hbv Replication ◽  
B Virus ◽  
Dose Corticosteroid

<b><i>Background:</i></b> Hepatitis B virus-associated glomerulonephritis (HBV-GN) can occur in patients with negative HBV serological antigens. Little is known about the treatment of seronegative HBV-GN (sn HBV-GN). The aim of this prospective study was to evaluate the efficacy and safety of corticosteroids in the treatment of sn HBV-GN. <b><i>Methods:</i></b> Twenty-six patients with nephrotic syndrome induced by seronegative HBV-associated membranous nephropathy were enrolled. The patients were given methylprednisolone (0.8 mg/kg/day) for 12–24 weeks, tapered by a 2-mg reduction every 1–3 months. Patients were followed up for 6–36 months. Complete remission (CR) was defined as proteinuria &#x3c;0.3 g/24 h. Partial remission (PR) was defined as proteinuria of 0.3–3.5 g/24 h that was reduced ≥50% of the baseline level. <b><i>Results:</i></b> The effective remission (including CR and PR) rates of nephrotic syndrome were 23.1%, 61.5%, 73.1%, 76.2%, 90.5%, and 81.0%, respectively, after 1, 3, 6, 12, 24, and 36 months. Nineteen patients achieved effective remission after 11.68 ± 7.15 months. The level of serum albumin improved from 24.34 ± 6.71 g/L at baseline to 39.61 ± 7.45 g/L at the 36th month significantly. After treatment, the level of serum Cr was similar to the baseline. Only 2 patients relapsed. The primary adverse reaction was infection. None of the patients showed evidence of HBV replication. <b><i>Conclusion:</i></b> The long-term middle-dose corticosteroid therapy without antiviral drugs is effective and safe for membranous sn HBV-GN patients. For sn HBV-GN patients, the monitoring of HBV DNA and HBV markers in the serum is necessary during the corticosteroid monotherapy. <b><i>Trial Registration:</i></b> The Chinese Clinical Trial Registry (ChiCTR1900022518).

scholarly journals Hematological Malignancies and HBV Reactivation: Suggestions for Clinical Management

2019 ◽  
Author(s):  
Alessandra Zannella ◽  
Massimo Marignani ◽  
Paola Begini
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hematological Malignancies ◽  
Immunosuppressive Drugs ◽  
Viral Reactivation ◽  
Hbv Reactivation ◽  
Virus Reactivation ◽  
Hepatitis B Virus Reactivation ◽  
B Virus ◽  
Clinical Consequences

It is well known that the event of hepatitis B virus reactivation can occur among patients undergoing treatment for hematological malignancies. In this paper we will present the available data regarding the risk of hepatitis B virus reactivation in this special population of immunosuppressed patients and explore the relevance of an accurate prevention and management of this condition. A computerized literature search was performed using appropriate terms arrangement, including English-written literature only or additional relevant articles. The evaluation of hepatitis B reactivation risk is a multidimensional process, which includes conducting an accurate clinical and physical history, considering the virological categories, the knowledge of the medication chosen to treat these hematological malignancies and the induced grade of immunosuppression. Adopting adequate preventive strategies and surveillance according to the current international recommendations is crucial to prevent HBVr and its dire clinical consequences (hepatitis, liver failure, interruption of lifesaving anti-neoplastic treatments). Universal HBV screening of patients scheduled to undergo treatment for hematological malignancies should be the chosen policy, and clinicians should be aware of the inherent risk of viral reactivation among the different virological categories and the classes of immunosuppressive drugs.

scholarly journals STING Agonists Induce an Innate Antiviral Immune Response against Hepatitis B Virus

2014 ◽  
Vol 59 (2) ◽  
pp. 1273-1281 ◽  
Author(s):  
Fang Guo ◽  
Yanxing Han ◽  
Xuesen Zhao ◽  
Jianghua Wang ◽  
Fei Liu ◽  
...  
Keyword(s):  
Immune Response ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Cytokine Response ◽  
Hbv Infection ◽  
Stable Cell Line ◽  
Type I ◽  
Antiviral Immune Response ◽  
Hbv Replication ◽  
B Virus

ABSTRACTChronicity of hepatitis B virus (HBV) infection is due to the failure of a host to mount a sufficient immune response to clear the virus. The aim of this study was to identify small-molecular agonists of the pattern recognition receptor (PRR)-mediated innate immune response to control HBV infection. To achieve this goal, a coupled mouse macrophage and hepatocyte culture system mimicking the intrahepatic environment was established and used to screen small-molecular compounds that activate macrophages to produce cytokines, which in turn suppress HBV replication in a hepatocyte-derived stable cell line supporting HBV replication in a tetracycline-inducible manner. An agonist of the mouse stimulator of interferon (IFN) genes (STING), 5,6-dimethylxanthenone-4-acetic acid (DMXAA), was found to induce a robust cytokine response in macrophages that efficiently suppressed HBV replication in mouse hepatocytes by reducing the amount of cytoplasmic viral nucleocapsids. Profiling of cytokines induced by DMXAA and agonists of representative Toll-like receptors (TLRs) in mouse macrophages revealed that, unlike TLR agonists that induced a predominant inflammatory cytokine/chemokine response, the STING agonist induced a cytokine response dominated by type I IFNs. Moreover, as demonstrated in an HBV hydrodynamic mouse model, intraperitoneal administration of DMXAA significantly induced the expression of IFN-stimulated genes and reduced HBV DNA replication intermediates in the livers of mice. This study thus proves the concept that activation of the STING pathway induces an antiviral cytokine response against HBV and that the development of small-molecular human STING agonists as immunotherapeutic agents for treatment of chronic hepatitis B is warranted.

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