Skip to main content

Hepatitis B Virus Infection: Overview

  • Chapter
  • First Online:
Hepatitis B Virus Infection

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1179))

Abstract

Hepatitis B virus (HBV) is a DNA virus, belonging to the Hepadnaviridae family. It is a partially double-stranded DNA virus with a small viral genome (3.2 kb). Chronic HBV infection remains a global public health problem. If left untreated, chronic HBV infection can progress to end-stage liver disease, such as liver cirrhosis and hepatocellular carcinoma (HCC). In recent years, tremendous advances in the field of HBV basic and clinical research have been achieved, ranging from the HBV biological characteristics, immunopathogenesis, and animal models to the development of new therapeutic strategies and new drugs against HBV. In this overview, we begin with a brief history of HBV discovery and treatment milestones. We then briefly summarize the HBV research advances, which will be detailed in the following chapters.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Maccallum FO (1946) Homologous serum hepatitis. Proc R Soc Med 39(10):655–657

    PubMed  PubMed Central  Google Scholar 

  2. Blumberg BS (1964) Polymorphisms of the serum proteins and the development of Iso-precipitins in transfused patients. Bull N Y Acad Med 40:377–386

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Blumberg BS, Alter HJ, Visnich S (1965) A “New” antigen in leukemia sera. JAMA 191:541–546

    Article  CAS  PubMed  Google Scholar 

  4. Blumberg BS, Gerstley BJ, Hungerford DA, London WT, Sutnick AI (1967) A serum antigen (Australia antigen) in Down’s syndrome, leukemia, and hepatitis. Ann Intern Med 66(5):924–931

    Article  CAS  PubMed  Google Scholar 

  5. Bayer ME, Blumberg BS, Werner B (1968) Particles associated with Australia antigen in the sera of patients with leukaemia, down’s syndrome and hepatitis. Nature 218(5146):1057–1059

    Article  CAS  PubMed  Google Scholar 

  6. Prince AM, Fuji H, Gershon RK (1964) Immunohistochemical studies on the etiology of anicteric hepatitis in Korea. Am J Hyg 79:365–381

    CAS  PubMed  Google Scholar 

  7. Prince AM (1968) An antigen detected in the blood during the incubation period of serum hepatitis. Proc Natl Acad Sci U S A 60(3):814–821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Prince AM (1968) Relation of Australia and SH antigens. Lancet 2(7565):462–463

    Article  CAS  PubMed  Google Scholar 

  9. Dane DS, Cameron CH, Briggs M (1970) Virus-like particles in serum of patients with Australia-antigen-associated hepatitis. Lancet 1(7649):695–698

    Article  CAS  PubMed  Google Scholar 

  10. Galibert F, Mandart E, Fitoussi F, Tiollais P, Charnay P (1979) Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli. Nature 281(5733):646–650

    Article  CAS  PubMed  Google Scholar 

  11. Szmuness W, Stevens CE, Harley EJ, Zang EA, Oleszko WR, William DC et al (1980) Hepatitis B vaccine: demonstration of efficacy in a controlled clinical trial in a high-risk population in the United States. N Engl J Med 303(15):833–841

    Article  CAS  PubMed  Google Scholar 

  12. Valenzuela P, Gray P, Quiroga M, Zaldivar J, Goodman HM, Rutter WJ (1979) Nucleotide sequence of the gene coding for the major protein of hepatitis B virus surface antigen. Nature 280(5725):815–819

    Article  CAS  PubMed  Google Scholar 

  13. Edman JC, Hallewell RA, Valenzuela P, Goodman HM, Rutter WJ (1981) Synthesis of hepatitis B surface and core antigens in E. coli. Nature 291(5815):503–506

    Article  CAS  PubMed  Google Scholar 

  14. Valenzuela P, Medina A, Rutter WJ, Ammerer G, Hall BD (1982) Synthesis and assembly of hepatitis B virus surface antigen particles in yeast. Nature 298(5872):347–350

    Article  CAS  PubMed  Google Scholar 

  15. McAleer WJ, Buynak EB, Maigetter RZ, Wampler DE, Miller WJ, Hilleman MR (1984) Human hepatitis B vaccine from recombinant yeast. Nature 307(5947):178–180

    Article  CAS  PubMed  Google Scholar 

  16. Brunetto MR (2010) A new role for an old marker, HBsAg. J Hepatol 52(4):475–477

    Article  CAS  PubMed  Google Scholar 

  17. Sonneveld MJ, Zoutendijk R, Janssen HL (2011) Hepatitis B surface antigen monitoring and management of chronic hepatitis B. J Viral Hepat 18(7):449–457

    Article  CAS  PubMed  Google Scholar 

  18. Trepo C (2014) A brief history of hepatitis milestones. Liver Int 34(Suppl 1):29–37

    Article  CAS  PubMed  Google Scholar 

  19. Dienstag JL, Schiff ER, Wright TL, Perrillo RP, Hann HW, Goodman Z et al (1999) Lamivudine as initial treatment for chronic hepatitis B in the United States. N Engl J Med 341(17):1256–1263

    Article  CAS  PubMed  Google Scholar 

  20. WHO (2017) Global hepatitis report, 2017. [updated April 2017; cited 2019 June 11]

    Google Scholar 

  21. Liang X, Bi S, Yang W, Wang L, Cui G, Cui F et al (2009) Epidemiological serosurvey of hepatitis B in China--declining HBV prevalence due to hepatitis B vaccination. Vaccine 27(47):6550–6557

    Article  PubMed  Google Scholar 

  22. Liang X, Bi S, Yang W, Wang L, Cui G, Cui F et al (2009) Evaluation of the impact of hepatitis B vaccination among children born during 1992–2005 in China. J Infect Dis 200(1):39–47

    Article  PubMed  Google Scholar 

  23. Lu FM, Zhuang H (2009) Management of hepatitis B in China. Chin Med J 122(1):3–4

    Article  PubMed  Google Scholar 

  24. Polaris Observatory C (2018) Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study. Lancet Gastroenterol Hepatol 3(6):383–403

    Article  Google Scholar 

  25. Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH et al (2016) AASLD guidelines for treatment of chronic hepatitis B. Hepatology (Baltimore, MD) 63(1):261–283

    Article  Google Scholar 

  26. Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM et al (2018) Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology (Baltimore, MD) 67(4):1560–1599

    Article  Google Scholar 

  27. European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL 2017 (2017) Clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol 67(2):370–398

    Article  Google Scholar 

  28. Hsu YS, Chien RN, Yeh CT, Sheen IS, Chiou HY, Chu CM et al (2002) Long-term outcome after spontaneous HBeAg seroconversion in patients with chronic hepatitis B. Hepatology (Baltimore, MD) 35(6):1522–1527

    Article  Google Scholar 

  29. Fattovich G, Bortolotti F, Donato F (2008) Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol 48(2):335–352

    Article  PubMed  CAS  Google Scholar 

  30. Chu CM, Liaw YF (2006) Hepatitis B virus-related cirrhosis: natural history and treatment. Semin Liver Dis 26(2):142–152

    Article  CAS  PubMed  Google Scholar 

  31. Chen YC, Chu CM, Yeh CT, Liaw YF (2007) Natural course following the onset of cirrhosis in patients with chronic hepatitis B: a long-term follow-up study. Hepatol Int 1(1):267–273

    Article  PubMed  PubMed Central  Google Scholar 

  32. WHO (2018) The top 10 causes of death. [updated May 24 2018; cited 2019 June 11]

    Google Scholar 

  33. Sureau C, Salisse J (2013) A conformational heparan sulfate binding site essential to infectivity overlaps with the conserved hepatitis B virus a-determinant. Hepatology (Baltimore, MD) 57(3):985–994

    Article  CAS  Google Scholar 

  34. Yan H, Zhong G, Xu G, He W, Jing Z, Gao Z et al (2012) Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. elife 1:e00049

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Hayes CN, Zhang Y, Makokha GN, Hasan MZ, Omokoko MD, Chayama K (2016) Early events in hepatitis B virus infection: from the cell surface to the nucleus. J Gastroenterol Hepatol 31(2):302–309

    Article  CAS  PubMed  Google Scholar 

  36. Nassal M (2015) HBV cccDNA: viral persistence reservoir and key obstacle for a cure of chronic hepatitis B. Gut 64(12):1972–1984

    Article  CAS  PubMed  Google Scholar 

  37. Jones SA, Hu J (2013) Protein-primed terminal transferase activity of hepatitis B virus polymerase. J Virol 87(5):2563–2576

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Nassal M (2008) Hepatitis B viruses: reverse transcription a different way. Virus Res 134(1–2):235–249

    Article  CAS  PubMed  Google Scholar 

  39. Hu J, Liu K (2017) Complete and incomplete hepatitis B virus particles: formation, function, and application. Viruses 9(3):56

    Article  PubMed Central  CAS  Google Scholar 

  40. Tang H, Banks KE, Anderson AL, McLachlan A (2001) Hepatitis B virus transcription and replication. Drug News Perspect 14(6):325–334

    CAS  PubMed  Google Scholar 

  41. Tang H, McLachlan A (2001) Transcriptional regulation of hepatitis B virus by nuclear hormone receptors is a critical determinant of viral tropism. Proc Natl Acad Sci U S A 98(4):1841–1846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Reese V, Ondracek C, Rushing C, Li L, Oropeza CE, McLachlan A (2011) Multiple nuclear receptors may regulate hepatitis B virus biosynthesis during development. Int J Biochem Cell Biol 43(2):230–237

    Article  CAS  PubMed  Google Scholar 

  43. Shalaby RE, Iram S, Cakal B, Oropeza CE, McLachlan A (2017) PGC1 alpha transcriptional adaptor function governs hepatitis B virus replication by controlling HBcAg/p21 protein-mediated capsid formation. J Virol 91(20)

    Google Scholar 

  44. Shalaby RE, Iram S, Oropeza CE, McLachlan A (2019) Peroxisome proliferator-activated receptor gamma coactivator family members competitively regulate hepatitis b virus biosynthesis. Virology 526:214–221

    Article  CAS  PubMed  Google Scholar 

  45. Reese VC, Moore DD, McLachlan A (2012) Limited effects of bile acids and small heterodimer partner on hepatitis B virus biosynthesis in vivo. J Virol 86(5):2760–2768

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Chen Y, Hu J, Cai X, Huang Y, Zhou X, Tu Z et al (2018) APOBEC3B edits HBV DNA and inhibits HBV replication during reverse transcription. Antivir Res 149:16–25

    Article  CAS  PubMed  Google Scholar 

  47. Xie N, Yuan K, Zhou L, Wang K, Chen HN, Lei Y et al (2016) PRKAA/AMPK restricts HBV replication through promotion of autophagic degradation. Autophagy 12(9):1507–1520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Zhang W, Chen J, Wu M, Zhang X, Zhang M, Yue L et al (2017) PRMT5 restricts hepatitis B virus replication through epigenetic repression of covalently closed circular DNA transcription and interference with pregenomic RNA encapsidation. Hepatology (Baltimore, MD) 66(2):398–415

    Article  CAS  Google Scholar 

  49. Gong DY, Chen EQ, Huang FJ, Leng XH, Cheng X, Tang H (2013) Role and functional domain of hepatitis B virus X protein in regulating HBV transcription and replication in vitro and in vivo. Viruses 5(5):1261–1271

    Article  PubMed  PubMed Central  Google Scholar 

  50. Tang H, Delgermaa L, Huang F, Oishi N, Liu L, He F et al (2005) The transcriptional transactivation function of HBx protein is important for its augmentation role in hepatitis B virus replication. J Virol 79(9):5548–5556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Bouchard MJ, Wang L, Schneider RJ (2006) Activation of focal adhesion kinase by hepatitis B virus HBx protein: multiple functions in viral replication. J Virol 80(9):4406–4414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Decorsiere A, Mueller H, van Breugel PC, Abdul F, Gerossier L, Beran RK et al (2016) Hepatitis B virus X protein identifies the Smc5/6 complex as a host restriction factor. Nature 531(7594):386–389

    Article  PubMed  CAS  Google Scholar 

  53. Murphy CM, Xu Y, Li F, Nio K, Reszka-Blanco N, Li X et al (2016) Hepatitis B virus X protein promotes degradation of SMC5/6 to enhance HBV replication. Cell Rep 16(11):2846–2854

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Guidotti LG, Chisari FV (2001) Noncytolytic control of viral infections by the innate and adaptive immune response. Annu Rev Immunol 19:65–91

    Article  CAS  PubMed  Google Scholar 

  55. Wu J, Meng Z, Jiang M, Pei R, Trippler M, Broering R et al (2009) Hepatitis B virus suppresses toll-like receptor-mediated innate immune responses in murine parenchymal and nonparenchymal liver cells. Hepatology (Baltimore, MD) 49(4):1132–1140

    Article  CAS  Google Scholar 

  56. Chen J, Wu M, Zhang X, Zhang W, Zhang Z, Chen L et al (2013) Hepatitis B virus polymerase impairs interferon-alpha-induced STA T activation through inhibition of importin-alpha5 and protein kinase C-delta. Hepatology (Baltimore, MD) 57(2):470–482

    Article  CAS  Google Scholar 

  57. Wei C, Ni C, Song T, Liu Y, Yang X, Zheng Z et al (2010) The hepatitis B virus X protein disrupts innate immunity by downregulating mitochondrial antiviral signaling protein. J Immunol (Baltimore, MD: 1950) 185(2):1158–1168

    Article  CAS  Google Scholar 

  58. Jiang J, Tang H (2010) Mechanism of inhibiting type I interferon induction by hepatitis B virus X protein. Protein Cell 1(12):1106–1117

    Article  CAS  PubMed  Google Scholar 

  59. Han Q, Zhang C, Zhang J, Tian Z (2011) Reversal of hepatitis B virus-induced immune tolerance by an immunostimulatory 3p-HBx-siRNAs in a retinoic acid inducible gene I-dependent manner. Hepatology (Baltimore, MD) 54(4):1179–1189

    Article  CAS  Google Scholar 

  60. Bertoletti A, Ferrari C (2012) Innate and adaptive immune responses in chronic hepatitis B virus infections: towards restoration of immune control of viral infection. Gut 61(12):1754–1764

    Article  CAS  PubMed  Google Scholar 

  61. Isogawa M, Tanaka Y (2015) Immunobiology of hepatitis B virus infection. Hepatol Res 45(2):179–189

    Article  CAS  PubMed  Google Scholar 

  62. Lin SM, Yu ML, Lee CM, Chien RN, Sheen IS, Chu CM et al (2007) Interferon therapy in HBeAg positive chronic hepatitis reduces progression to cirrhosis and hepatocellular carcinoma. J Hepatol 46(1):45–52

    Article  CAS  PubMed  Google Scholar 

  63. Wong DK, Cheung AM, O’Rourke K, Naylor CD, Detsky AS, Heathcote J (1993) Effect of alpha-interferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B. A meta-analysis. Ann Intern Med 119(4):312–323

    Article  CAS  PubMed  Google Scholar 

  64. Lau GK, Piratvisuth T, Luo KX, Marcellin P, Thongsawat S, Cooksley G et al (2005) Peginterferon Alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med 352(26):2682–2695

    Article  CAS  PubMed  Google Scholar 

  65. Piratvisuth T, Lau G, Chao YC, Jin R, Chutaputti A, Zhang QB et al (2008) Sustained response to peginterferon alfa-2a (40 kD) with or without lamivudine in Asian patients with HBeAg-positive and HBeAg-negative chronic hepatitis B. Hepatol Int 2(1):102–110

    Article  PubMed  PubMed Central  Google Scholar 

  66. Janssen HL, van Zonneveld M, Senturk H, Zeuzem S, Akarca US, Cakaloglu Y et al (2005) Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial. Lancet 365(9454):123–129

    Article  CAS  PubMed  Google Scholar 

  67. Lai CL, Dienstag J, Schiff E, Leung NW, Atkins M, Hunt C et al (2003) Prevalence and clinical correlates of YMDD variants during lamivudine therapy for patients with chronic hepatitis B. Clin Infect Dis 36(6):687–696

    Article  CAS  PubMed  Google Scholar 

  68. Han GR, Cao MK, Zhao W, Jiang HX, Wang CM, Bai SF et al (2011) A prospective and open-label study for the efficacy and safety of telbivudine in pregnancy for the prevention of perinatal transmission of hepatitis B virus infection. J Hepatol 55(6):1215–1221

    Article  CAS  PubMed  Google Scholar 

  69. Han GR, Jiang HX, Yue X, Ding Y, Wang CM, Wang GJ et al (2015) Efficacy and safety of telbivudine treatment: an open-label, prospective study in pregnant women for the prevention of perinatal transmission of hepatitis B virus infection. J Viral Hepat 22(9):754–762

    Article  CAS  PubMed  Google Scholar 

  70. Marcellin P, Chang TT, Lim SG, Sievert W, Tong M, Arterburn S et al (2008) Long-term efficacy and safety of adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. Hepatology (Baltimore, MD) 48(3):750–758

    Article  CAS  Google Scholar 

  71. Seto WK, Lai CL, Fung J, Wong DK, Yuen JC, Hung IF et al (2011) Significance of HBV DNA levels at 12 weeks of telbivudine treatment and the 3 years treatment outcome. J Hepatol 55(3):522–528

    Article  CAS  PubMed  Google Scholar 

  72. Yokosuka O, Takaguchi K, Fujioka S, Shindo M, Chayama K, Kobashi H et al (2010) Long-term use of entecavir in nucleoside-naive Japanese patients with chronic hepatitis B infection. J Hepatol 52(6):791–799

    Article  CAS  PubMed  Google Scholar 

  73. Kitrinos KM, Corsa A, Liu Y, Flaherty J, Snow-Lampart A, Marcellin P et al (2014) No detectable resistance to tenofovir disoproxil fumarate after 6 years of therapy in patients with chronic hepatitis B. Hepatology (Baltimore, MD) 59(2):434–442

    Article  CAS  Google Scholar 

  74. Marcellin P, Lau GK, Bonino F, Farci P, Hadziyannis S, Jin R et al (2004) Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. N Engl J Med 351(12):1206–1217

    Article  CAS  PubMed  Google Scholar 

  75. Stelma F, van der Ree MH, Jansen L, Peters MW, Janssen HLA, Zaaijer HL et al (2017) HBsAg loss after peginterferon-nucleotide combination treatment in chronic hepatitis B patients: 5 years of follow-up. J Viral Hepat 24(12):1107–1113

    Article  CAS  PubMed  Google Scholar 

  76. Marcellin P, Ahn SH, Ma X, Caruntu FA, Tak WY, Elkashab M et al (2016) Combination of tenofovir disoproxil fumarate and peginterferon alpha-2a increases loss of hepatitis B surface antigen in patients with chronic hepatitis B. Gastroenterology 150(1):134–144. e10

    Article  CAS  PubMed  Google Scholar 

  77. de Niet A, Jansen L, Stelma F, Willemse SB, Kuiken SD, Weijer S et al (2017) Peg-interferon plus nucleotide analogue treatment versus no treatment in patients with chronic hepatitis B with a low viral load: a randomised controlled, open-label trial. Lancet Gastroenterol Hepatol 2(8):576–584

    Article  PubMed  Google Scholar 

  78. Marcellin P, Ahn SH, Chuang WL, Hui AJ, Tabak F, Mehta R et al (2016) Predictors of response to tenofovir disoproxil fumarate plus peginterferon alfa-2a combination therapy for chronic hepatitis B. Aliment Pharmacol Ther 44(9):957–966

    Article  CAS  PubMed  Google Scholar 

  79. Brouwer WP, Xie Q, Sonneveld MJ, Zhang N, Zhang Q, Tabak F et al (2015) Adding pegylated interferon to entecavir for hepatitis B e antigen-positive chronic hepatitis B: a multicenter randomized trial (ARES study). Hepatology (Baltimore, MD) 61(5):1512–1522

    Article  CAS  Google Scholar 

  80. van Campenhout MJH, Brouwer WP, Xie Q, Guo S, Chi H, Qi X et al (2019) Long-term follow-up of patients treated with entecavir and peginterferon add-on therapy for HBeAg-positive chronic hepatitis B infection: ARES long-term follow-up. J Viral Hepat 26(1):109–117

    Article  PubMed  CAS  Google Scholar 

  81. Bourliere M, Rabiega P, Ganne-Carrie N, Serfaty L, Marcellin P, Barthe Y et al (2017) Effect on HBs antigen clearance of addition of pegylated interferon alfa-2a to nucleos(t)ide analogue therapy versus nucleos(t)ide analogue therapy alone in patients with HBe antigen-negative chronic hepatitis B and sustained undetectable plasma hepatitis B virus DNA: a randomised, controlled, open-label trial. Lancet Gastroenterol Hepatol 2(3):177–188

    Article  PubMed  Google Scholar 

  82. Ning Q, Han M, Sun Y, Jiang J, Tan D, Hou J et al (2014) Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: a randomised open-label trial (OSST trial). J Hepatol 61(4):777–784

    Article  CAS  PubMed  Google Scholar 

  83. Hu P, Shang J, Zhang W, Gong G, Li Y, Chen X et al (2018) HBsAg loss with peg-interferon Alfa-2a in hepatitis B patients with partial response to Nucleos(t)ide analog: new switch study. J Clin Transl Hepatol 6(1):25–34

    PubMed  PubMed Central  Google Scholar 

  84. Blank A, Markert C, Hohmann N, Carls A, Mikus G, Lehr T et al (2016) First-in-human application of the novel hepatitis B and hepatitis D virus entry inhibitor myrcludex B. J Hepatol 65(3):483–489

    Article  CAS  PubMed  Google Scholar 

  85. Blank A, Eidam A, Haag M, Hohmann N, Burhenne J, Schwab M et al (2018) The NTCP-inhibitor Myrcludex B: effects on bile acid disposition and Tenofovir pharmacokinetics. Clin Pharmacol Ther 103(2):341–348

    Article  CAS  PubMed  Google Scholar 

  86. Gaj T, Gersbach CA, Barbas CF 3rd. (2013) ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol 31(7):397–405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Sander JD, Joung JK (2014) CRISPR-Cas systems for editing, regulating and targeting genomes. Nat Biotechnol 32(4):347–355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Schiffer JT, Aubert M, Weber ND, Mintzer E, Stone D, Jerome KR (2012) Targeted DNA mutagenesis for the cure of chronic viral infections. J Virol 86(17):8920–8936

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Dong C, Qu L, Wang H, Wei L, Dong Y, Xiong S (2015) Targeting hepatitis B virus cccDNA by CRISPR/Cas9 nuclease efficiently inhibits viral replication. Antivir Res 118:110–117

    Article  CAS  PubMed  Google Scholar 

  90. Kennedy EM, Bassit LC, Mueller H, Kornepati AVR, Bogerd HP, Nie T et al (2015) Suppression of hepatitis B virus DNA accumulation in chronically infected cells using a bacterial CRISPR/Cas RNA-guided DNA endonuclease. Virology 476:196–205

    Article  CAS  PubMed  Google Scholar 

  91. Joung JK, Sander JD (2013) TALENs: a widely applicable technology for targeted genome editing. Nat Rev Mol Cell Biol 14(1):49–55

    Article  CAS  PubMed  Google Scholar 

  92. Wooddell CI, Yuen MF, Chan HL, Gish RG, Locarnini SA, Chavez D et al (2017) RNAi-based treatment of chronically infected patients and chimpanzees reveals that integrated hepatitis B virus DNA is a source of HBsAg. Sci Trans Med 9(409)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Lam AM, Espiritu C, Vogel R, Ren S, Lau V, Kelly M et al (2019) Preclinical characterization of NVR 3-778, a first-in-class capsid assembly modulator against hepatitis B virus. Antimicrob Agents Chemother 63(1)

    Google Scholar 

  94. Klumpp K, Shimada T, Allweiss L, Volz T, Lutgehetmann M, Hartman G et al (2018) Efficacy of NVR 3-778, alone and in combination with pegylated interferon, vs entecavir in uPA/SCID mice with humanized livers and HBV infection. Gastroenterology 154(3):652–662. e8

    Article  CAS  PubMed  Google Scholar 

  95. Yuen MF, Gane EJ, Kim DJ, Weilert F, Yuen Chan HL, Lalezari J et al (2019) Antiviral activity, safety, and pharmacokinetics of capsid assembly modulator NVR 3-778 in patients with chronic HBV infection. Gastroenterology

    Google Scholar 

  96. Zoulim F, Yogaratnam J, Vandenbossche JJ, Moscalu I, Streinu-Cercel A, Lenz O et al (2019) Safety, pharmacokinetics and antiviral activity of a novel hepatitis B virus capsid assembly modulator, JNJ-56136379, in Patients with Chronic Hepatitis B. APASL. Adv Ther 36(9):2450–2462

    Article  CAS  Google Scholar 

  97. Zhang HZX, Chen H et al (2018) Safety, Pharmacokinetics and anti-viral efficacy of novel core protein allosteric modifier GLS4 in patients with chronic hepatitis B: interim results from a 48 weeks phase 2a Study. AASLD 2018 Abstract LB-13

    Google Scholar 

  98. Ma XL Lalezari J et al (2019) Interim safety and efficacy results of the ABI-H0731 phase 2a program exploring the combination of ABI-H0731 with Nuc therapy in treatment-naive and treatment-suppressed chronic hepatitis B patients. EASL 2019 Abs LBO-06. Hepatology 70(1):e130

    Google Scholar 

  99. Lampertico P (2014) Oral antiviral therapy for hepatitis B: the case of besifovir, a new kid on the block with a long way to go. Gut 63(6):869–870

    Article  CAS  PubMed  Google Scholar 

  100. Lai CL, Ahn SH, Lee KS, Um SH, Cho M, Yoon SK et al (2014) Phase IIb multicentred randomised trial of besifovir (LB80380) versus entecavir in Asian patients with chronic hepatitis B. Gut 63(6):996–1004

    Article  CAS  PubMed  Google Scholar 

  101. Ahn SH, Kim W, Jung YK, Yang JM, Jang JY, Kweon YO et al (2019) Efficacy and safety of besifovir dipivoxil maleate compared with tenofovir disoproxil fumarate in treatment of chronic hepatitis B virus infection. Clin Gastroenterol Hepatol 17(9):1850–1859.e4

    Article  CAS  PubMed  Google Scholar 

  102. Feng S, Gao L, Han X, Hu T, Hu Y, Liu H et al (2018) Discovery of small molecule therapeutics for treatment of chronic HBV infection. ACS Infect Dis 4(3):257–277

    Article  CAS  PubMed  Google Scholar 

  103. Painter GR, Almond MR, Trost LC, Lampert BM, Neyts J, De Clercq E et al (2007) Evaluation of hexadecyloxypropyl-9-R-[2-(Phosphonomethoxy)propyl]- adenine, CMX157, as a potential treatment for human immunodeficiency virus type 1 and hepatitis B virus infections. Antimicrob Agents Chemother 51(10):3505–3509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Cai CW, Lomonosova E, Moran EA, Cheng X, Patel KB, Bailly F et al (2014) Hepatitis B virus replication is blocked by a 2-hydroxyisoquinoline-1,3(2H,4H)-dione (HID) inhibitor of the viral ribonuclease H activity. Antivir Res 108:48–55

    Article  CAS  PubMed  Google Scholar 

  105. Edwards TC, Lomonosova E, Patel JA, Li Q, Villa JA, Gupta AK et al (2017) Inhibition of hepatitis B virus replication by N-hydroxyisoquinolinediones and related polyoxygenated heterocycles. Antivir Res 143:205–217

    Article  CAS  PubMed  Google Scholar 

  106. Grant E, Joshi A, Ayithan N, Daffis S, Woo J, Lam T et al (2018) Pharmacodynamic response to oral administration of the selective toll-like receptor 8 agonist GS-9688 in healthy volunteers. Hepatology (Baltimore, MD) 68:270a–a

    Google Scholar 

  107. Lanford RE, Guerra B, Chavez D, Giavedoni L, Hodara VL, Brasky KM et al (2013) GS-9620, an oral agonist of Toll-like receptor-7, induces prolonged suppression of hepatitis B virus in chronically infected chimpanzees. Gastroenterology 144(7).:1508–1517, 17.e1–17.e10

    Article  CAS  Google Scholar 

  108. Wenjin Z, Chuanhui P, Yunle W, Lateef SA, Shusen Z (2012) Longitudinal fluctuations in PD1 and PD-L1 expression in association with changes in anti-viral immune response in chronic hepatitis B. BMC Gastroenterol 12:109

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C et al (2017) Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet 389(10088):2492–2502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Boni C, Janssen HLA, Rossi M, Yoon SK, Vecchi A, Barili V et al (2019) Combined GS-4774 and tenofovir therapy can improve HBV-specific T-cell responses in patients with chronic hepatitis. Gastroenterology 157(1):227–241.e7

    Article  CAS  PubMed  Google Scholar 

  111. Lok AS, Pan CQ, Han SH, Trinh HN, Fessel WJ, Rodell T et al (2016) Randomized phase II study of GS-4774 as a therapeutic vaccine in virally suppressed patients with chronic hepatitis B. J Hepatol 65(3):509–516

    Article  CAS  PubMed  Google Scholar 

  112. Martin P, Dubois C, Jacquier E, Dion S, Mancini-Bourgine M, Godon O et al (2015) TG1050, an immunotherapeutic to treat chronic hepatitis B, induces robust T cells and exerts an antiviral effect in HBV-persistent mice. Gut 64(12):1961–1971

    Article  CAS  PubMed  Google Scholar 

  113. Liang TJ, Block TM, McMahon BJ, Ghany MG, Urban S, Guo JT et al (2015) Present and future therapies of hepatitis B: from discovery to cure. Hepatology (Baltimore, MD) 62(6):1893–1908

    Article  Google Scholar 

  114. Brahmania M, Feld J, Arif A, Janssen HL (2016) New therapeutic agents for chronic hepatitis B. Lancet Infect Dis 16(2):e10–e21

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from the National Natural Science Foundation of China (No.81772193).

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Li, H. et al. (2020). Hepatitis B Virus Infection: Overview. In: Tang, H. (eds) Hepatitis B Virus Infection. Advances in Experimental Medicine and Biology, vol 1179. Springer, Singapore. https://doi.org/10.1007/978-981-13-9151-4_1

Download citation

Publish with us

Policies and ethics