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The Interaction between Host Immunity and Hepatitis B Virus Infection
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The Interaction between Host Immunity and Hepatitis B Virus Infection

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 17520

Special Issue Editor

Prof. Dr. Yi-Hsiang Huang

E-Mail Website
Guest Editor
1. School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
2. Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
Interests: HBV
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Hepatitis B virus (HBV) infection is the major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. There are more than two-hundred million people worldwide chronically infected with HBV. Both host and viral factors are involved in the pathogenesis of HBV infection. Host immune responses to HBV, including innate and adaptive immunity are responsible for HBV control and clearance. Functional cure of HBV, indicating loss of HBV surface antigen (HBsAg) is a treatment goal for chronic HBV infection, that requiring effective host immunity against HBV. However, even after controlling HBV, HBV reactivation would occur during chemotherapy or immunosuppressive treatment in cases whose HBV infection had resolved. In this special issue of IJMS, original articles or systemic reviews related to host-viral (HBV) interaction are highly welcome, such as strategies to break the immune tolerance in chronic hepatitis B; synergy of innate and adaptive immunity for chronic hepatitis B infection, novel immunotherapeutic methods to achieve functional cure of HBV; update of HBV reactivation risk and mechanism associated with immunosuppressant, or biologics treatment in HBsAg positive or negative patients.

Prof. Yi-Hsiang Huang
Guest Editor

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Keywords

  • HBV reactivation
  • biologics
  • immunosuppressive treatment
  • innate immunity
  • adaptive immunity
  • HBsAg reverse seroconversion

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Published Papers (4 papers)

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Research

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13 pages, 1437 KiB  
Article
High Risk of Viral Reactivation in Hepatitis B Patients with Systemic Lupus Erythematosus
by Ming-Han Chen, Chien-Sheng Wu, Ming-Huang Chen, Chang-Youh Tsai, Fa-Yauh Lee and Yi-Hsiang Huang
Int. J. Mol. Sci. 2021, 22(17), 9116; https://doi.org/10.3390/ijms22179116 - 24 Aug 2021
Cited by 9 | Viewed by 2756
Abstract
HBV reactivation (HBVr) can occur in hepatitis B surface antigen (HBsAg)-positive and negative patients. Here, we determined the incidence of HBVr and its related hepatitis in patients with systemic lupus erythematosus (SLE). From 2000 to 2017, 3307 SLE cases were retrospectively reviewed for [...] Read more.
HBV reactivation (HBVr) can occur in hepatitis B surface antigen (HBsAg)-positive and negative patients. Here, we determined the incidence of HBVr and its related hepatitis in patients with systemic lupus erythematosus (SLE). From 2000 to 2017, 3307 SLE cases were retrospectively reviewed for episodes of hepatitis. The incidence, long-term outcomes and risk factors associated with HBVr, including HBsAg reverse seroconversion (RS) were analyzed. Among them, 607 had available HBsAg status. Fifty-five (9.1%) patients were positive for HBsAg and 63 (11.4%) were HBsAg-negative/antibody to hepatitis B core antigen (anti-HBc)-positive (resolved hepatitis B infection, RHB). None of them received antiviral prophylaxis before immunosuppressive treatment. During a mean 15.4 years of follow-up, 30 (54.5%) HBsAg-positive patients developed HBVr and seven (23.3%) died of liver failure, whereas only two (3.2%) RHB cases experienced HBsAg reverse seroconversion (RS). Multivariate logistic regression analysis showed that age ≥ 40 years at diagnosis of SLE (HR 5.30, p < 0.001), receiving glucocorticoid-containing immunosuppressive therapy (HR 4.78, p = 0.003), and receiving glucocorticoid ≥ 10 mg prednisolone equivalents (HR 3.68, p = 0.003) were independent risk factors for HBVr in HBsAg-positive patients. Peak level of total bilirubin ≥ 5 mg/dL during HBVr was an independent factor of mortality (p = 0.002). In conclusion, the risk of HBVr was associated with glucocorticoid daily dose. Antiviral prophylaxis is mandatory for SLE patients diagnosed at age of ≥40 years who receive ≥ 10 mg daily dose of oral prednisone or equivalent. Full article
(This article belongs to the Special Issue The Interaction between Host Immunity and Hepatitis B Virus Infection)
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Review

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23 pages, 1428 KiB  
Review
Hepatitis B Flare in Hepatitis B e Antigen-Negative Patients: A Complicated Cascade of Innate and Adaptive Immune Responses
by Ming-Ling Chang and Yun-Fan Liaw
Int. J. Mol. Sci. 2022, 23(3), 1552; https://doi.org/10.3390/ijms23031552 - 28 Jan 2022
Cited by 27 | Viewed by 6999
Abstract
Chronic hepatitis B virus (HBV) infection is a dynamic process involving interactions among HBV, hepatocytes, and the host immune system. The natural course of chronic hepatitis B (CHB) is divided into four chronological phases, including the hepatitis B e antigen (HBeAg)-positive and HBeAg-negative [...] Read more.
Chronic hepatitis B virus (HBV) infection is a dynamic process involving interactions among HBV, hepatocytes, and the host immune system. The natural course of chronic hepatitis B (CHB) is divided into four chronological phases, including the hepatitis B e antigen (HBeAg)-positive and HBeAg-negative phases. During HBV flare, alanine aminotransferase (ALT) levels abruptly rise to >5× the upper limit of normal; this is thought to occur due to the immune response against an upsurge in serum HBV DNA and antigen levels. Hepatitis flares may occur spontaneously, during or after antiviral therapy, or upon immunosuppression or chemotherapy in both HBeAg-positive and HBeAg-negative patients. The clinical spectrum of HBV flares varies from asymptomatic to hepatic decompensation or failure. HBeAg seroconversion with ≥ 1 year of consolidation therapy is accepted as an endpoint of oral antiviral therapy in HBeAg-positive patients, but recommendations for treating HBeAg-negative patients differ. Thus, the management of HBeAg-negative patients has attracted increasing interest. In the current review, we summarize various types of HBV flares and the associated complex cascade of innate and adaptive immune responses, with a focus on HBeAg-negative CHB patients. Hopefully, this review will provide insight into immunopathogenesis to improve the management of HBV flares in HBeAg-negative CHB patients. Full article
(This article belongs to the Special Issue The Interaction between Host Immunity and Hepatitis B Virus Infection)
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15 pages, 324 KiB  
Review
Immunopathogenesis of Acute Flare of Chronic Hepatitis B: With Emphasis on the Role of Cytokines and Chemokines
by Chieh Liu, Yi-Fen Shih and Chun-Jen Liu
Int. J. Mol. Sci. 2022, 23(3), 1407; https://doi.org/10.3390/ijms23031407 - 26 Jan 2022
Cited by 4 | Viewed by 2645
Abstract
Acute flares (AFs) of chronic hepatitis B usually occur during the immune-active stage (both immune clearance phase and immune reactivation phase), as the host immune system tries to control the virus. Successful host immune control over viral replication is usually presented as hepatitis [...] Read more.
Acute flares (AFs) of chronic hepatitis B usually occur during the immune-active stage (both immune clearance phase and immune reactivation phase), as the host immune system tries to control the virus. Successful host immune control over viral replication is usually presented as hepatitis B surface antigen seroclearance; however, 20–30% individuals with chronic hepatitis B may encounter repeated AFs with accumulative liver injuries, finally leading to the development of cirrhosis and hepatocellular carcinoma. AF can also develop in other clinical situations such as organ transplantation, cancer chemotherapy, and under treatment for chronic hepatitis B or treatment for chronic hepatitis C in patients with co-infected hepatitis B/hepatitis C. Understanding the natural history and immunopathogenesis of AF would help develop effective strategies to eradicate the virus and improve the clinical outcomes of patients with chronic hepatitis B. In this review article, the immunopathogenesis of AF, and the involvement of innate and adaptive immune responses on the development of hepatitis B flare will be briefly reviewed, with the emphasis on the role of cytokines and chemokines. Full article
(This article belongs to the Special Issue The Interaction between Host Immunity and Hepatitis B Virus Infection)
15 pages, 1508 KiB  
Review
Toll-Like Receptor Response to Hepatitis B Virus Infection and Potential of TLR Agonists as Immunomodulators for Treating Chronic Hepatitis B: An Overview
by Mohammad Enamul Hoque Kayesh, Michinori Kohara and Kyoko Tsukiyama-Kohara
Int. J. Mol. Sci. 2021, 22(19), 10462; https://doi.org/10.3390/ijms221910462 - 28 Sep 2021
Cited by 39 | Viewed by 4228
Abstract
Chronic hepatitis B virus (HBV) infection remains a major global health problem. The immunopathology of the disease, especially the interplay between HBV and host innate immunity, is poorly understood. Moreover, inconsistent literature on HBV and host innate immunity has led to controversies. However, [...] Read more.
Chronic hepatitis B virus (HBV) infection remains a major global health problem. The immunopathology of the disease, especially the interplay between HBV and host innate immunity, is poorly understood. Moreover, inconsistent literature on HBV and host innate immunity has led to controversies. However, recently, there has been an increase in the number of studies that have highlighted the link between innate immune responses, including Toll-like receptors (TLRs), and chronic HBV infection. TLRs are the key sensing molecules that detect pathogen-associated molecular patterns and regulate the induction of pro- and anti-inflammatory cytokines, thereby shaping the adaptive immunity. The suppression of TLR response has been reported in patients with chronic hepatitis B (CHB), as well as in other models, including tree shrews, suggesting an association of TLR response in HBV chronicity. Additionally, TLR agonists have been reported to improve the host innate immune response against HBV infection, highlighting the potential of these agonists as immunomodulators for enhancing CHB treatment. In this study, we discuss the current understanding of host innate immune responses during HBV infection, particularly focusing on the TLR response and TLR agonists as immunomodulators. Full article
(This article belongs to the Special Issue The Interaction between Host Immunity and Hepatitis B Virus Infection)
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