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Chronic hepatitis B: the demise of the ‘inactive carrier’ phase

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Abstract

Chronic hepatitis B (CHB) remains a global healthcare burden. Although the recent developments in the field have led to a reduction in incidence, the morbidity and mortality including liver cirrhosis and hepatocellular carcinoma (HCC) remain a formidable challenge. Advances in understanding the immunopathogenesis of CHB have led to a recent change in clinical categorization. EASL introduced the term hepatitis B ‘e’ antigen (HBeAg)-negative chronic infection, to replace the historical term ‘inactive carrier’ disease phase, the commonest CHB phase. Although this disease phase is associated with a favorable prognosis, it is not a truly ‘inactive’ disease phase with no ostensible liver disease, as inferred by the previous anachronistic terminology, and the risk of spontaneous reactivation and the potential risk of disease progression and HCC development are not negligible. Likewise, the APASL also uses the term “Incidentally Detected Asymptomatic Hepatitis B surface antigen (HBsAg)-positive Subject (IDAHS)”, comprising all HBsAg-positive subjects who are incidentally detected during routine tests, without any previous or present symptoms of liver disease. This entity includes HBV infection with varied stages of liver disease. Antiviral treatment is generally reserved for patients with active inflammation and/or at risk of disease progression and HCC development. HBsAg loss is considered an optimal treatment endpoint, and may also be achievable in HBeAg-negative chronic infection and IDAHS. In light of this, and the emerging novel HBV therapies, lowering the treatment threshold and a ‘Treat All’ approach should now be considered. In this review, we summarize the literature and guidance on HBeAg-negative chronic infection, and we make a concerted effort to present the reasons why the one-dimensional term ‘inactive carrier’ should be abandoned.

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References

  1. European Association for the Study of the Liver. EASL 2017 Clinical Practice guidelines on the management of hepatitis B virus infection. J Hepatol 2017;67:370–398

    Article  Google Scholar 

  2. Chen C-L, Yang J-Y, Lin S-F, et al. Slow decline of hepatitis B burden in general population: results from a population-based survey and longitudinal follow-up study in Taiwan. J Hepatol 2015;63:354–363

    Article  PubMed  Google Scholar 

  3. Coppola N, Alessio L, Gualdieri L, et al. Hepatitis B virus, hepatitis C virus and human immunodeficiency virus infection in undocumented migrants and refugees in southern Italy, January 2012 to June 2013. Euro Surveill 2015;20:30009

    Article  PubMed  Google Scholar 

  4. Hampel A, Solbach P, Cornberg M, Schmidt RE, Behrens GM, Jablonka A. Current seroprevalence, vaccination and predictive value of liver enzymes for hepatitis B among refugees in Germany. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2016;59:578–583

    Article  PubMed  Google Scholar 

  5. Ott JJ, Stevens GA, Groeger J, Wiersma ST. Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine 2012;30:2212–2219

    Article  CAS  PubMed  Google Scholar 

  6. Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet 2015;386:1546–1555

    Article  PubMed  Google Scholar 

  7. Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380:2095–2128

    Article  PubMed  Google Scholar 

  8. Sarin SK, Kumar M, Lau GK, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int 2016;10(1):1–98

    Article  CAS  PubMed  Google Scholar 

  9. WHO. World Health Organization factsheet: hepatitis B 2017. Available from: http://www.who.int/mediacentre/factsheets/fs204/en/

  10. Dolman GE, Koffas A, Mason WS, Kennedy PT. Why, who and when to start treatment for chronic hepatitis B infection. Curr Opin Virol 2018;30:39–47

    Article  PubMed  Google Scholar 

  11. Gill US, Kennedy PTF. New insights in the management of chronic hepatitis B. Clin Med (Lond) 2015;15(2):191–196

    Article  Google Scholar 

  12. Tong S, Revill P. Overview of hepatitis B viral replication and genetic variability. J Hepatol 2016;64:S4–S16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Valaydon ZS, Locarnini SA. The virological aspects of hepatitis B. Best Pract Res Clin Gastroenterol 2017;31:257–264

    Article  CAS  PubMed  Google Scholar 

  14. Lucifora J, Protzer U. Attacking hepatitis B virus cccDNA—the holy grail to hepatitis B cure. J Hepatol 2016;64:S41–S48

    Article  CAS  PubMed  Google Scholar 

  15. Tu T, Budzinska MA, Shackel NA, Urban S. HBV DNA integration: molecular mechanisms and clinical implications. Viruses 2017;9:E75

    Article  PubMed  Google Scholar 

  16. Budzinska MA, Shackel NA, Urban S, Tu T. Sequence analysis of integrated hepatitis B virus DNA during HBeAg-seroconversion. Emerg Microbes Infect 2018;7(1):142

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  18. Mason WS, Gill US, Litwin S, et al. HBV DNA integration and clonal hepatocyte expansion in chronic hepatitis B patients considered immune tolerant. Gastroenterology 2016;151:986–998

    Article  CAS  PubMed  Google Scholar 

  19. Kramvis A. Genotypes and genetic variability of hepatitis B virus. Intervirology 2014;57:141–150

    Article  PubMed  Google Scholar 

  20. You J, Sriplung H, Geater A, et al. Effect of viral load on T-lymphocyte failure in patients with chronic hepatitis B. World J Gastroenterol 2008;14:1112–1119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Chen M, Sällberg M, Hughes J, et al. Immune tolerance split between hepatitis B virus precore and core proteins. J Virol 2005;79:3016–3027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Malmström S, Larsson SB, Hannoun C, Lindh M. Hepatitis B viral DNA decline at loss of HBeAg is mainly explained by reduced cccDNA load–down-regulated transcription of PgRNA has limited impact. PLoS ONE 2012;7:e36349

    Article  PubMed  PubMed Central  Google Scholar 

  23. Iorio R, Giannattasio A, Cirillo F, D’Alessandro L, Vegnente A. Long-term outcome in children with chronic hepatitis B: a 24-year observation period. Clin Infect Dis 2007;45(8):943–949

    Article  PubMed  Google Scholar 

  24. WHO. Hepatitis B vaccines: WHO position paper—July 2017. Wkly Epidemiol Rec 2017;92:369–392

    Google Scholar 

  25. WHO (2020) Hepatitis B. https://www.who.int/news-room/fact-sheets/detail/hepatitis-b. Accessed Dec 2020

  26. Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 2018;67:1560–1599

    Article  PubMed  PubMed Central  Google Scholar 

  27. Koffas A et al. Reasons to consider early treatment in chronic hepatitis B patients. Antiviral Res 2020;177:104783.

    Article  CAS  PubMed  Google Scholar 

  28. Kennedy PT, Sandalova E, Jo J, et al. Preserved T-cell function in children and young adults with immune-tolerant chronic hepatitis B. Gastroenterology 2012;143:637–645

    Article  CAS  PubMed  Google Scholar 

  29. Kumar M, Sarin SK, Hissar S, et al. Virological and histological features of chronic hepatitis b virus infected asymptomatic patients with persistently normal ALT. Gastroenterology 2008;134(5):1376–1384

    Article  PubMed  Google Scholar 

  30. Kumar M, Sarin SK. Hepatitis B virus immune-tolerant patients: need to differentiate patients with or without liver disease. Gastroenterology 2009;137(2):742–743

    Article  PubMed  Google Scholar 

  31. Lin CL, Liao LY, Liu CJ, et al. Hepatitis B viral factors in HBeAg-negative carriers with persistently normal serum alanine aminotransferase levels. Hepatology 2007;45(5):1193–1198

    Article  CAS  PubMed  Google Scholar 

  32. Chen YC, Huang SF, Chu CM, Liaw YF. Serial HBV DNA levels in patients with persistently normal transaminase over 10 years following spontaneous HBeAg seroconversion. J Viral Hepat 2012;19:138–146

    Article  CAS  PubMed  Google Scholar 

  33. Papatheodoridis GV, Manolakopoulos S, Liaw YF, Lok A. Follow-up and indications for liver biopsy in HBeAg-negative chronic hepatitis B virus infection with persistently normal ALT: a systematic review. J Hepatol 2012;57:196–202

    Article  PubMed  Google Scholar 

  34. Tseng TC, Liu CJ, Yang HC, et al. High levels of hepatitis B surface antigen increase risk of hepatocellular carcinoma in patients with low HBV load. Gastroenterology 2012;142(5):1140–1149

    Article  CAS  PubMed  Google Scholar 

  35. Cornberg M, Wong VW, Locarnini S, Brunetto M, Janssen HLA, Chan HL. The role of quantitative hepatitis B surface antigen revisited. J Hepatol 2017;66(2):398–411

    Article  CAS  PubMed  Google Scholar 

  36. Liu J, Lee MH, Batrla-Utermann R, et al. A predictive scoring system for the seroclearance of HBsAg in HBeAg-seronegative chronic hepatitis B patients with genotype B or C infection. J Hepatol 2013;58(5):853–860

    Article  CAS  PubMed  Google Scholar 

  37. Martinot-Peignoux M, Asselah T, Marcellin P. HBsAg quantification to optimize treatment monitoring in chronic hepatitis B patients. Liver Int 2015;35(1):82–90

    Article  CAS  PubMed  Google Scholar 

  38. Kim JH, Ghosh A, Ayithan N, et al. Circulating serum HBsAg level is a biomarker for HBV-specific T and B cell responses in chronic hepatitis B patients. Sci Rep 2020;10(1):1835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Le Bert N, Gill US, Hong M, et al. Effects of hepatitis B surface antigen on virus-specific and global T cells in patients with chronic HBV infection. Gastroenterology 2020;S0016–5085(20):30492–30493

    Google Scholar 

  40. Chu CM, Liaw YF. Spontaneous relapse of hepatitis in inactive HBsAg carriers. Hepatol Int 2007;1:311–315

    Article  PubMed  PubMed Central  Google Scholar 

  41. Kumar M, Chauhan R, Gupta N, Hissar SS, Sakhuja P, Sarin SK. Spontaneous increase in ALT levels in asymptomatic chronic hepatitis B virus infected patients. Gastroenterology 2009;136(4):1272–1280

    Article  CAS  PubMed  Google Scholar 

  42. Fattovich G, Olivari N, Pasino M, D’Onofrio M, Martone E, Donato F. Long-term outcome of chronic hepatitis B in Caucasian patients: mortality after 25 years. Gut 2008;57(1):84–90

    Article  CAS  PubMed  Google Scholar 

  43. Chu CM, Liaw YF. Predictive factors for reactivation of hepatitis B following hepatitis B e antigen seroconversion in chronic hepatitis B. Gastroenterology 2007;133(5):1458–1465

    Article  CAS  PubMed  Google Scholar 

  44. Tassopoulos NC, Papaevangelou GJ, Sjogren MH, et al. Natural history of acute hepatitis B surface antigen-positive hepatitis in Greek adults. Gastroenterology 1987;92:1844–1850

    Article  CAS  PubMed  Google Scholar 

  45. Kumar M, Sharma BC, Sarin SK. Hepatitis E virus as an etiology of acute exacerbation of previously unrecognized asymptomatic patients with hepatitis B virus-related chronic liver disease. J Gastroenterol Hepatol 2008;23(6):883–887

    Article  PubMed  Google Scholar 

  46. Martinot-Peignoux M, Boyer N, Colombat M, et al. Serum hepatitis B virus DNA levels and liver histology in inactive HBsAg carriers. J Hepatol 2002;36:543–546

    Article  CAS  PubMed  Google Scholar 

  47. Koffas A, Dolman GE, Kennedy PT. Hepatitis B virus reactivation in patients treated with immunosuppressive drugs: a practical guide for clinicians. Clin Med (Lond) 2018;18(3):212–218

    Article  Google Scholar 

  48. Yeo YH, Ho HJ, Yang HI, et al. Factors associated with rates of HBsAg seroclearance in adults with chronic HBV infection: a systematic review and meta-analysis. Gastroenterology 2019;156(3):635.e9–646.e9

    Article  Google Scholar 

  49. Zhou K, Contag C, Whitaker E, Terrault N. Spontaneous loss of surface antigen among adults living with chronic hepatitis B virus infection: a systematic review and pooled meta-analyses lancet. Gastroenterol Hepatol 2019;4(3):227–238

    Google Scholar 

  50. Yuen MF, Wong DK, Fung J, et al. HBsAg sero-clearance in chronic hepatitis B in Asian patients: replicative level and risk of hepatocellular carcinoma. Gastroenterology 2008;135:1192–1199

    Article  CAS  PubMed  Google Scholar 

  51. Kao JH, Chen PJ, Lai MY, Chen DS. Hepatitis B genotypes correlate with clinical outcomes in patients with chronic hepatitis B. Gastroenterology 2000;118:554–559

    Article  CAS  PubMed  Google Scholar 

  52. Sumi H, Yokosuka O, Seki N, et al. Influence of hepatitis B virus genotypes on the progression of chronic type B liver disease. Hepatology 2003;37:19–26

    Article  CAS  PubMed  Google Scholar 

  53. Tseng TC, Liu CJ, Yang HC, et al. Higher proportion of viral basal core promoter mutant increases the risk of liver cirrhosis in hepatitis B carriers. Gut 2015;64(2):292–302

    Article  CAS  PubMed  Google Scholar 

  54. Degertekin B, Lok ASF. Update on viral hepatitis: 2008. Curr Opin Gastroenterol 2009;25(3):180–185

    Article  PubMed  Google Scholar 

  55. Kumar M, Sarin SK. Liver biopsy in chronic hepatitis B virus infected patients with normal ALT. Reply. Gastroenterology 2008;135(5):1802–1803

    Article  Google Scholar 

  56. Tai DI, Lin SM, Sheen IS, et al. Long-term outcome of hepatitis B e antigen-negative hepatitis B surface antigen carriers in relation to changes of alanine aminotransferase levels over time. Hepatology 2009;49(6):1859–1867

    Article  CAS  PubMed  Google Scholar 

  57. Chen JD, Yang HI, Iloeje UH, Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer in HBV (REVEAL-HBV) Study Group, et al. Carriers of inactive hepatitis B virus are still at risk for hepatocellular carcinoma and liver-related death. Gastroenterology 2010;138(5):1747–1754

    Article  PubMed  Google Scholar 

  58. Iloeje UH, Yang HI, Chen CJ. Natural history of chronic hepatitis B: what exactly has REVEAL revealed? Liver Int 2012;32:1333–1341

    Article  PubMed  Google Scholar 

  59. Tseng TC, Liu CJ, Yang HC, et al. Serum hepatitis B surface antigen levels help predict disease progression in patients with low hepatitis B virus loads. Hepatology 2013;57:441–450

    Article  CAS  PubMed  Google Scholar 

  60. Ellard J, Wallace J. Stigma, Discrimination and Hepatitis B: A Review of Current Research (ARCSHS Monograph Series No. 93). Melbourne: Australian Research Centre in Sex, Health and Society, La Trobe University; 2013

    Google Scholar 

  61. Corrigan PW, Watson AC. Understanding the impact of stigma on people with mental illness. World Psychiatry 2002;1(1):16–20

    PubMed  PubMed Central  Google Scholar 

  62. Vaughn-Sandler V, Sherman C, Aronsohn A, Volk ML. Consequences of perceived stigma among patients with cirrhosis. Dig Dis Sci 2014;59:681–686

    Article  PubMed  Google Scholar 

  63. Liu K. Hepatitis B infection in China: the stigma behind the stigmata. Liver Int 2016;36(11):1582–1584

    Article  PubMed  Google Scholar 

  64. Cotler SJ, Cotler S, Xie H, et al. Characterizing hepatitis B stigma in Chinese immigrants. J Viral Hepat 2012;19:147–152

    Article  CAS  PubMed  Google Scholar 

  65. Yu L, Wang J, Zhu D, Leng A, Wangen KR. Hepatitis B related knowledge and vaccination in association with discrimination against Hepatitis B in rural China. Hum Vaccin Immunother 2016;12:70–76

    Article  PubMed  Google Scholar 

  66. Na L, Na B. A revolutionary road: an analysis of persons living with hepatitis B in China. J Health Commun 2013;18:71–91

    Article  PubMed  Google Scholar 

  67. Mokaya J, McNaughton AL, Burbridge L. A blind spot? Confronting the stigma of hepatitis B virus (HBV) infection—a systematic review. Version 2. Wellcome Open Res 2018;3:29

    Article  PubMed  PubMed Central  Google Scholar 

  68. Lancet T. Towards elimination of viral hepatitis by 2030. Lancet 2016;388:308

    Article  Google Scholar 

  69. Lok AS, Zoulim F, Dusheiko G, Ghany MG. Hepatitis B cure: from discovery to regulatory approval. Hepatology 2017;66(4):1296–1313

    Article  PubMed  PubMed Central  Google Scholar 

  70. Webster GJ, Reignat S, Brown D, et al. Longitudinal analysis of CD8+ T cells specific for structural and nonstructural hepatitis B virus proteins in patients with chronic hepatitis B: implications for immunotherapy. J Virol 2004;78:5707–5719

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Boni C, Fisicaro P, Valdatta C, et al. Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection. J Virol 2007;81:4215–4225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Schmidt J, Blum HE, Thimme R. T-cell responses in hepatitis B and C virus infection: similarities and differences. Emerg Microbes Infect 2013;2:e15

    Article  PubMed  PubMed Central  Google Scholar 

  73. Fang Z, Li J, Yu X, et al. Polarization of monocytic myeloid-derived suppressor cells by hepatitis B surface antigen is mediated via ERK/IL-6/STAT3 signaling feedback and restrains the activation of T cells in chronic hepatitis B virus infection. J Immunol 2015;195:4873–4883

    Article  CAS  PubMed  Google Scholar 

  74. Pal S, Nandi M, Dey D, et al. Myeloid derived suppressor cells induce regulatory T cells in chronically HBV infected patients with high levels of hepatitis B surface antigen and persist after antiviral therapy. Aliment Pharmacol Ther 2019;49:1346–1359

    Article  CAS  PubMed  Google Scholar 

  75. Le Bert N, Salimzadeh L, Gill US, et al. Comparative characterization of B cells specific for HBV nucleocapsid and envelope proteins in patients with chronic hepatitis B. J Hepatol 2020;72(1):34–44

    Article  PubMed  Google Scholar 

  76. Burton AR, Pallett LJ, McCoy LE, et al. Circulating and intrahepatic antiviral B cells are defective in hepatitis B. J Clin Invest 2018;128(10):4588–4603

    Article  PubMed  PubMed Central  Google Scholar 

  77. Salimzadeh L, Le Bert N, Dutertre CA, et al. PD-1 blockade partially recovers dysfunctional virusspecific B cells in chronic hepatitis B infection. J Clin Invest 2018;128(10):4573–4587

    Article  PubMed  PubMed Central  Google Scholar 

  78. Kim GA, Lim YS, An J, et al. HBsAg seroclearance after nucleoside analogue therapy in patients with chronic hepatitis B: clinical outcomes and durability. Gut 2014;63:1325–1332

    Article  CAS  PubMed  Google Scholar 

  79. Alawad AS, Auh S, Suarez D, et al. Durability of spontaneous and treatment-related loss of hepatitis B s antigen. Clin Gastroenterol Hepatol 2020;18:700–709

    Article  CAS  PubMed  Google Scholar 

  80. Chi H, Wong D, Peng J, et al. Durability of response after hepatitis B surface antigen seroclearance during nucleos(t)ide analogue treatment in a multiethnic cohort of chronic hepatitis B patients: results after treatment cessation. Clin Infect Dis 2017;65:680–683

    Article  PubMed  Google Scholar 

  81. Wu Y, Liu Y, Lu J, et al. Durability of interferon-induced hepatitis B surface antigen seroclearance. Clin Gastroenterol Hepatol 2020;18(514–516):e2

    Google Scholar 

  82. Yip TC, Wong GL, Wong VW, et al. Durability of hepatitis B surface antigen seroclearance in untreated and nucleos(t)ide analogue-treated patients. J Hepatol 2017;68:63–72

    Article  Google Scholar 

  83. Lau GKK, Suri D, Liang R, et al. Resolution of chronic hepatitis B and anti-HBs seroconversion in humans by adoptive transfer of immunity to hepatitis B core antigen. Gastroenterology 2002;122(3):614–624

    Article  CAS  PubMed  Google Scholar 

  84. Tseng TC, Kao JH. Clinical utility of quantitative HBsAg in natural history and nucleos(t)ide analogue treatment of chronic hepatitis B: new trick of old dog. J Gastroenterol 2013;48:13–21

    Article  CAS  PubMed  Google Scholar 

  85. Cornberg M, Lok ASF, Terrault NA, Zoulim Z, the 2019 EASL-AASLD HBV Treatment Endpoints Conference. Guidance for design and endpoints of clinical trials in chronic hepatitis B—report from the 2019 EASL-AASLD HBV treatment endpoints conference. Hepatology 2020;71(3):1070–1092

    Article  Google Scholar 

  86. Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection: Recommendations for a Public Health Approach (2016) World Health Organization, Geneva. https://www.who.int/hiv/pub/arv/arv-2016/en. Accessed 2 Dec 2019

  87. (2018) Guidelines for the care and treatment of persons diagnosed with chronic hepatitis C virus infection. World Health Organization, Geneva. https://apps.who.int/iris/bitstream/handle/10665/273174/9789241550345-eng.pdf. Accessed 2 Dec 2019

  88. Toy M, Salomon JA, Jiang H, et al. Population health impact and cost effectiveness of monitoring inactive chronic hepatitis B and treating eligible patients in Shanghai, China. Hepatology 2014;60(1):46–55

    Article  PubMed  Google Scholar 

  89. Appendix A Population health impact and cost-effectiveness of chronic hepatitis B diagnosis, care, and treatment in the United States. A National Strategy for the elimination of hepatitis B and C phase two report. Authors: National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Population Health and Public Health Practice; Committee on a National Strategy for the Elimination of Hepatitis B and C. Editors: Brian L. Strom and Gillian J. Buckley. Washington (DC): National Academies Press (US); 2017 Mar 28

  90. Kumar M, Sarin SK. Viral hepatitis eradication in India by 2080—gaps, challenges and targets. Indian J Med Res 2014;140:1–4

    PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Gastroenterology, General University Hospital of Larisa, Larisa, Greece

    Apostolos Koffas

  2. Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India

    Manoj Kumar, Ankur Jindal & S. K. Sarin

  3. Barts Liver Centre, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK

    Upkar S. Gill & Patrick T. F. Kennedy

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  1. Apostolos Koffas
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  2. Manoj Kumar
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Koffas, A., Kumar, M., Gill, U.S. et al. Chronic hepatitis B: the demise of the ‘inactive carrier’ phase. Hepatol Int 15, 290–300 (2021). https://doi.org/10.1007/s12072-021-10137-2

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