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Immunological Features of AECHB

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Acute Exacerbation of Chronic Hepatitis B

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Abstract

This chapter describes the immunologic features of liver, the immune mediated pathogenesis of both innate and adaptive immune system, the key role of immune coagulation, antiviral therapy and immune response in AECHB and HBV ACLF.

  1. 1.

    The liver is an organ with predominant innate immunity, playing an important role not only in host defenses but also in liver injury and repair. The liver is continuously exposed to a large antigenic load that includes pathogens, toxins, tumor cells and harmless dietary antigens. The range of local immune mechanisms required to cope with this diverse immunological challenge is now being appreciated. The liver contains large numbers of phagocytic cells, antigen-presenting cells and lymphocytes. The liver comprises enrichment of large numbers of non-specific immune cells, including natural killer (NK) cells, T cells expressing γδ (γδT cells) and T cells expressing NK molecules (NKT cells). These cells are crucial for early defenses against viral infection through direct cytotoxic and non-cytolytic mechanisms. In addition, these cells participate in the progression of severe hepatitis B by initiating specific immune response (Doherty DG, O’Farrelly C, Immunol Rev. 174:5–20, 2000; Racanelli V, Rehermann B. Hepatology 43(2 Suppl 1):S54–62, 2006; Crispe IN. Annu Rev Immunol. 27:147–163, 2009; Gong FL. Medical immunology, 4th ed. Science Publishing House, pp. 371–377).

  2. 2.

    As the first sensor to recognize HBV and its products, pattern recognition receptors (PRRs) such as toll--like receptors (TLRs), induce the expression of immune related genes and proinflammatory genes by activating intracellular signal transduction pathways. These pathways induce inflammatory and anti-viral responses that affect the occurrence and development of severe hepatitis B.

  3. 3.

    Clinical outcomes of viral infection are closely related to the specificity and intensity of specific immune responses. During the development of severe hepatitis B, the host immune response is characterized by dysfunction of antigen specific CTLs and imbalance of T lymphocyte subsets. Large numbers of infiltrated non-specific inflammatory cells and apoptosis of hepatocytes were also observed in liver tissue from patients. The liver immune system is characterized by the unique tolerance nature of liver. HBV persistence induces systemic adaptive cellular and humoral immunotolerance, which severely impairs the HBV clearance.

  4. 4.

    Most coagulation factors, anticoagulant proteins and components of the fibrinolytic system are synthesized and cleared in the liver. Severe hepatitis or liver failure can cause coagulation abnormalities, including microcirculation disorders of the liver induced by macrophages and fibrinogen-like protein 2(fgl2) prothrombinase, peripheral circulation dysfunction induced by impaired liver function, as well as disseminated intravascular coagulation (DIC). Coagulation failure has been typically thought of as one of the six most characteristic organ/system failure(s) during ACLF progress.

  5. 5.

    Currently approved anti-viral treatment options includes Nucleos(t)ide analogues (NAs) and interferon-a (IFN-a). NAs and Peg-IFN have differential effects on the innate and adaptive immune responses. Early anti-viral treatment can not only inhibit virus replication, but also help in the recovery of host immunity.

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  1. Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Ping Lei & Guan-Xin Shen

  2. Beijing 302 Hospital, Beijing, China

    Fu-Sheng Wang

  3. Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Qin Ning, Wei-Ming Yan & Di Wu

  4. ChongQing Medical University, Chongqing, China

    Hong Ren

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Lei, P. et al. (2019). Immunological Features of AECHB. In: Ning, Q. (eds) Acute Exacerbation of Chronic Hepatitis B. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-1606-0_5

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