Characteristics of the hepatitis B virus and pathogenesis of infection
- Anna SF Lok, MD
Anna SF Lok, MD
- Professor of Medicine
- University of Michigan Medical School
- Section Editors
- Rafael Esteban, MD
Rafael Esteban, MD
- Section Editor — Hepatitis B
- Professor of Medicine
- Hospital General Valle Hebrón
- Sheldon L Kaplan, MD
Sheldon L Kaplan, MD
- Editor-in-Chief — Pediatrics
- Section Editor — Pediatric Infectious Diseases
- Professor and Vice Chairman for Clinical Affairs
- Baylor College of Medicine
Hepatitis B virus (HBV) infection is a global public health problem. The spectrum of clinical manifestations of HBV infection varies in both acute and chronic disease. During the acute phase, manifestations range from subclinical hepatitis to anicteric hepatitis, icteric hepatitis, and fulminant hepatitis; during the chronic phase, manifestations range from an asymptomatic carrier state to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The clinical outcome of HBV infection depends upon the age at infection, the level of HBV replication, and the immune status of the host. (See "Clinical manifestations and natural history of hepatitis B virus infection".)
This topic review will discuss the characteristics of the hepatitis B virus and the pathogenesis of HBV-related liver disease. The immune response to HBV contributes to the hepatic injury, helps control the infection, and provides the means for establishing the serologic diagnosis of HBV infection. (See "Diagnosis of hepatitis B virus infection".)
CHARACTERISTICS OF THE VIRUS
Hepatitis B virus belongs to the family of hepadnaviruses, which include duck hepatitis virus, woodchuck hepatitis virus, and ground squirrel hepatitis virus. The complete virion or Dane particle is 42 nm in diameter. It consists of:
●An envelope composed of viral-encoded proteins and host-derived lipid components
●A core particle made up of the nucleocapsid protein, the viral genome, and the polymerase protein
- Scaglioni PP, Melegari M, Wands JR. Recent advances in the molecular biology of hepatitis B virus. Baillieres Clin Gastroenterol 1996; 10:207.
- Durantel D, Zoulim F. New antiviral targets for innovative treatment concepts for hepatitis B virus and hepatitis delta virus. J Hepatol 2016; 64:S117.
- Yan H, Zhong G, Xu G, et al. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. Elife 2012; 1:e00049.
- Ferrari C. HBV and the immune response. Liver Int 2015; 35 Suppl 1:121.
- Ma Z, Zhang E, Yang D, Lu M. Contribution of Toll-like receptors to the control of hepatitis B virus infection by initiating antiviral innate responses and promoting specific adaptive immune responses. Cell Mol Immunol 2015; 12:273.
- Zhang E, Lu M. Toll-like receptor (TLR)-mediated innate immune responses in the control of hepatitis B virus (HBV) infection. Med Microbiol Immunol 2015; 204:11.
- Bertoletti A, Ferrari C. Adaptive immunity in HBV infection. J Hepatol 2016; 64:S71.
- Liaw YF, Pao CC, Chu CM, et al. Changes of serum hepatitis B virus DNA in two types of clinical events preceding spontaneous hepatitis B e antigen seroconversion in chronic type B hepatitis. Hepatology 1987; 7:1.
- Perrillo RP. The management of chronic hepatitis B. Am J Med 1994; 96:34S.
- Rehermann B, Lau D, Hoofnagle JH, Chisari FV. Cytotoxic T lymphocyte responsiveness after resolution of chronic hepatitis B virus infection. J Clin Invest 1996; 97:1655.
- Bertoletti A, Hong M. Age-Dependent Immune Events during HBV Infection from Birth to Adulthood: An Alternative Interpretation. Front Immunol 2014; 5:441.
- Rehermann B, Ferrari C, Pasquinelli C, Chisari FV. The hepatitis B virus persists for decades after patients' recovery from acute viral hepatitis despite active maintenance of a cytotoxic T-lymphocyte response. Nat Med 1996; 2:1104.
- Bernuau J, Goudeau A, Poynard T, et al. Multivariate analysis of prognostic factors in fulminant hepatitis B. Hepatology 1986; 6:648.
- Webster GJ, Reignat S, Maini MK, et al. Incubation phase of acute hepatitis B in man: dynamic of cellular immune mechanisms. Hepatology 2000; 32:1117.
- Lok AS, Lai CL. A longitudinal follow-up of asymptomatic hepatitis B surface antigen-positive Chinese children. Hepatology 1988; 8:1130.
- Lau JY, Bain VG, Davies SE, et al. High-level expression of hepatitis B viral antigens in fibrosing cholestatic hepatitis. Gastroenterology 1992; 102:956.
- Carman WF, Trautwein C, van Deursen FJ, et al. Hepatitis B virus envelope variation after transplantation with and without hepatitis B immune globulin prophylaxis. Hepatology 1996; 24:489.
- Sato S, Suzuki K, Akahane Y, et al. Hepatitis B virus strains with mutations in the core promoter in patients with fulminant hepatitis. Ann Intern Med 1995; 122:241.
- Baumert TF, Rogers SA, Hasegawa K, Liang TJ. Two core promotor mutations identified in a hepatitis B virus strain associated with fulminant hepatitis result in enhanced viral replication. J Clin Invest 1996; 98:2268.
- Akarca US, Greene S, Lok AS. Detection of precore hepatitis B virus mutants in asymptomatic HBsAg-positive family members. Hepatology 1994; 19:1366.
- Carman WF, Jacyna MR, Hadziyannis S, et al. Mutation preventing formation of hepatitis B e antigen in patients with chronic hepatitis B infection. Lancet 1989; 2:588.
- Lok AS, Akarca U, Greene S. Mutations in the pre-core region of hepatitis B virus serve to enhance the stability of the secondary structure of the pre-genome encapsidation signal. Proc Natl Acad Sci U S A 1994; 91:4077.
- Incident Investigation Teams and Others. Transmission of hepatitis B to patients from four infected surgeons without hepatitis B e antigen. N Engl J Med 1997; 336:178.
- Bertoletti A, Naoumov NV. Translation of immunological knowledge into better treatments of chronic hepatitis B. J Hepatol 2003; 39:115.
- Rehermann B, Chang KM, McHutchinson J, et al. Differential cytotoxic T-lymphocyte responsiveness to the hepatitis B and C viruses in chronically infected patients. J Virol 1996; 70:7092.
- Penna A, Artini M, Cavalli A, et al. Long-lasting memory T cell responses following self-limited acute hepatitis B. J Clin Invest 1996; 98:1185.
- Michalak TI, Pasquinelli C, Guilhot S, Chisari FV. Hepatitis B virus persistence after recovery from acute viral hepatitis. J Clin Invest 1994; 93:230.
- Stoop JN, van der Molen RG, Baan CC, et al. Regulatory T cells contribute to the impaired immune response in patients with chronic hepatitis B virus infection. Hepatology 2005; 41:771.