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Current advances in the elimination of hepatitis B in China by 2030

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Abstract

With its 78 million chronic carriers, hepatitis B virus (HBV) infection is still one of the leading public health challenges in China. Over the last two decades, China has made great progress on the prevention of HBV transmission through national vaccination programs. Zero transmission from mother to infant has been proposed as the current goal. Available anti-HBV therapy is efficacious in suppressing HBV replication; however, it fails to completely cure patients with chronic hepatitis B and even requires lifelong treatment. To reduce the costs and improve the efficacy, several trials have been recently conducted in China to optimize the current anti-HBV managements. Novel biomarkers were identified to predict treatment outcomes, and new promising treatment strategies were developed. Reports also indicate that coinfections of HBV with other hepatotropic viruses and human immunodeficiency virus are common in China and cause severe liver diseases, which should be recognized early and treated properly. Work is still needed to eliminate hepatitis B in China by 2030.

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References

  1. World Health Organizaiton. Global Hepatitis Report 2017. 2017:3

    Google Scholar 

  2. Cui F, Zhuang H. Hepatitis B control in China: progress, challenges and strategies. Chin J Vir Dis (Zhongguo Bing Du Bing Za Zhi) 2016; 6: 81–87 (in Chinese)

    Google Scholar 

  3. Liao X, Liang Z. Strategy vaccination against Hepatitis B in China. Hum Vaccin Immunother 2015; 11(6): 1534–1539

    PubMed  PubMed Central  Google Scholar 

  4. Liang X, Cui F, Hadler S, Wang X, Luo H, Chen Y, Kane M, Shapiro C, Yang W, Wang Y. Origins, design and implementation of the China GAVI project. Vaccine 2013; 31(Suppl 9): J8–J14

    Article  PubMed  Google Scholar 

  5. Wang AL, Qiao YP, Wang LH, Fang LW, Wang F, Jin X, Qiu J, Wang XY, Wang Q, Wu JL, Vermund SH, Song L. Integrated prevention of mother-to-child transmission for human immunodeficiency virus, syphilis and hepatitis B virus in China. Bull World Health Organ 2015; 93(1): 52–56

    Article  PubMed  Google Scholar 

  6. Liang X, Bi S, Yang W, Wang L, Cui G, Cui F, Zhang Y, Liu J, Gong X, Chen Y, Wang F, Zheng H, Wang F, Guo J, Jia Z, Ma J, Wang H, Luo H, Li L, Jin S, Hadler SC, Wang Y. Evaluation of the impact of hepatitis B vaccination among children born during 1992–2005 in China. J Infect Dis 2009; 200(1): 39–47

    Article  PubMed  Google Scholar 

  7. Liang X, Bi S, Yang W, Wang L, Cui G, Cui F, Zhang Y, Liu J, Gong X, Chen Y, Wang F, Zheng H, Wang F, Guo J, Jia Z, Ma J, Wang H, Luo H, Li L, Jin S, Hadler SC, Wang Y. Epidemiological serosurvey of hepatitis B in China—declining HBV prevalence due to hepatitis B vaccination. Vaccine 2009; 27(47): 6550–6557

    Article  PubMed  Google Scholar 

  8. Cui F, Shen L, Li L, Wang H, Wang F, Bi S, Liu J, Zhang G, Wang F, Zheng H, Sun X, Miao N, Yin Z, Feng Z, Liang X, Wang Y. Prevention of chronic hepatitis B after 3 decades of escalating vaccination policy, China. Emerg Infect Dis 2017; 23(5): 765–772

    Article  PubMed  PubMed Central  Google Scholar 

  9. Qu C, Chen T, Fan C, Zhan Q, Wang Y, Lu J, Lu LL, Ni Z, Huang F, Yao H, Zhu J, Fan J, Zhu Y, Wu Z, Liu G, Gao W, Zang M, Wang D, Dai M, Hsia CC, Zhang Y, Sun Z. Efficacy of neonatal HBV vaccination on liver cancer and other liver diseases over 30-year follow-up of the Qidong hepatitis B intervention study: a cluster randomized controlled trial. PLoS Med 2014; 11(12): e1001774

    Article  PubMed  PubMed Central  Google Scholar 

  10. Zhuang H. Several issues regarding prevention of mother-to-child transmission of hepatitis B virus. J Clin Hepatol 2016; 32: 2227–2230

    Google Scholar 

  11. Zou H, Chen Y, Duan Z, Zhang H, Pan C. Virologic factors associated with failure to passive-active immunoprophylaxis in infants born to HBsAg-positive mothers. J Viral Hepat 2012; 19(2): e18–e25

    Article  CAS  PubMed  Google Scholar 

  12. Yi P, Chen R, Huang Y, Zhou RR, Fan XG. Management of motherto- child transmission of hepatitis B virus: propositions and challenges. J Clin Virol 2016; 77: 32–39

    Article  PubMed  Google Scholar 

  13. Pan CQ, Duan Z, Dai E, Zhang S, Han G, Wang Y, Zhang H, Zou H, Zhu B, Zhao W, Jiang H; China Study Group for the Mother-to-Child Transmission of Hepatitis B. Tenofovir to prevent hepatitis B transmission in mothers with high viral load. N Engl J Med 2016; 374(24): 2324–2334

    Article  CAS  PubMed  Google Scholar 

  14. Fan R, Yin X, Liu Z, Liu Z, Lau G, Hou J. A hepatitis B-free generation in China: from dream to reality. Lancet Infect Dis 2016; 16(10): 1103–1105

    Article  PubMed  Google Scholar 

  15. Yu R, Fan R, Hou J. Chronic hepatitis B virus infection: epidemiology, prevention, and treatment in China. Front Med 2014; 8(2): 135–144

    Article  PubMed  Google Scholar 

  16. Zhang W, Xie Q, Ning Q, Dou X, Chen X, Jia J, Xie Y, Ren H. The role of peginterferon in nucleos(t)ide-analogue-treated chronic hepatitis B patients: a review of published literature. J Viral Hepat 2017; 24(8): 618–623

    Article  CAS  PubMed  Google Scholar 

  17. Sun J, Xie Q, Tan D, Ning Q, Niu J, Bai X, Fan R, Chen S, Cheng J, Yu Y, Wang H, Xu M, Shi G, Wan M, Chen X, Tang H, Sheng J, Dou X, Shi J, Ren H, Wang M, Zhang H, Gao Z, Chen C, Ma H, Jia J, Hou J. The 104-week efficacy and safety of telbivudine-based optimization strategy in chronic hepatitis B patients: a randomized, controlled study. Hepatology 2014; 59(4): 1283–1292

    Article  CAS  PubMed  Google Scholar 

  18. Han M, Jiang J, Hou J, Tan D, Sun Y, Zhao M, Ning Q. Sustained immune control in HBeAg-positive patients who switched from entecavir therapy to pegylated interferon-α2a: 1 year follow-up of the OSST study. Antivir Ther 2016; 21(4): 337–344

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  20. Ren H, Hu P, Chen X, Gong G, Shang J, Zhang W, Li Y, Jiang J, Xie Q, Dou X. Switching to PegIFN a-2a in NUC treated CHB patients (NEW SWITCH study): comparison 48 and 96 weeks. Hepatol Int 2016; 10: O101 (meeting abstract; APASL 2016, Feb 20–24, Tokyo, Japan)

    Google Scholar 

  21. Brouwer WP, Xie Q, Sonneveld MJ, Zhang N, Zhang Q, Tabak F, Streinu-Cercel A, Wang JY, Idilman R, Reesink HW, Diculescu M, Simon K, Voiculescu M, Akdogan M, Mazur W, Reijnders JG, Verhey E, Hansen BE, Janssen HL; ARES Study Group. Adding pegylated interferon to entecavir for hepatitis B e antigen-positive chronic hepatitis B: A multicenter randomized trial (ARES study). Hepatology 2015; 61(5): 1512–1522

    Article  CAS  PubMed  Google Scholar 

  22. Chi H, Xie Q, Zhang N, Qi X, Chen L, Guo S, Guo Q, Arends P, Wang J, Verhry E, et al. Final results of Peginterferon Alfa-2b addon during long-term Nucleos(t)ide Analogue therapy in HBeAgpositive patients- a multicenter randomized controlled trial (PEGON study). Hepatology 2015; 62: 2002 (meeting abstract; AASLD 2015, Nov 13 17, San Francisco, USA)

    Google Scholar 

  23. Bourlière M, Rabiega P, Ganne-Carrie N, Serfaty L, Marcellin P, Barthe Y, Thabut D, Guyader D, Hezode C, Picon M, Causse X, Leroy V, Bronowicki JP, Carrieri P, Riachi G, Rosa I, Attali P, Molina JM, Bacq Y, Tran A, Grangé JD, Zoulim F, Fontaine H, Alric L, Bertucci I, Bouvier-Alias M, Carrat F; ANRS HB06 PEGAN Study Group. 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 2017; 2(3): 177–188

    Article  PubMed  Google Scholar 

  24. Cao Z, Liu Y, Ma L, Lu J, Jin Y, Ren S, He Z, Shen C, Chen X. A potent hepatitis B surface antigen response in subjects with inactive hepatitis B surface antigen carrier treated with pegylated-interferon alpha. Hepatology 2017; 66(4): 1058–1066

    Article  CAS  PubMed  Google Scholar 

  25. Sun J, Ma H, Xie Q, Xie Y, Sun Y, Wang H, Shi G, Wan M, Niu J, Ning Q, Yu Y, Zhou H, Cheng J, Kang W, Xie Y, Fan R, Wei L, Zhuang H, Jia J, Hou J. Response-guided peginterferon therapy in patients with HBeAg-positive chronic hepatitis B: a randomized controlled study. J Hepatol 2016; 65(4): 674–682

    Article  CAS  PubMed  Google Scholar 

  26. Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, Chen DS, Chen HL, Chen PJ, Chien RN, Dokmeci AK, Gane E, Hou JL, Jafri W, Jia J, Kim JH, Lai CL, Lee HC, Lim SG, Liu CJ, Locarnini S, Al Mahtab M, Mohamed R, Omata M, Park J, Piratvisuth T, Sharma BC, Sollano J, Wang FS, Wei L, Yuen MF, Zheng SS, Kao JH. 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 

  27. Liang TJ, Block TM, McMahon BJ, Ghany MG, Urban S, Guo JT, Locarnini S, Zoulim F, Chang KM, Lok AS. Present and future therapies of hepatitis B: from discovery to cure. Hepatology 2015; 62(6): 1893–1908

    Article  PubMed  PubMed Central  Google Scholar 

  28. Li J, Bao M, Ge J, Ren S, Zhou T, Qi F, Pu X, Dou J. Research progress of therapeutic vaccines for treating chronic hepatitis B. Hum Vaccin Immunother 2017; 13(5): 986–997

    Article  PubMed  PubMed Central  Google Scholar 

  29. Xu DZ, Zhao K, Guo LM, Li LJ, Xie Q, Ren H, Zhang JM, Xu M, Wang HF, Huang WX, Bai XF, Niu JQ, Liu P, Chen XY, Shen XL, Yuan ZH, Wang XY, Wen YM. A randomized controlled phase IIb trial of antigen-antibody immunogenic complex therapeutic vaccine in chronic hepatitis B patients. PLoS One 2008; 3(7): e2565

    Article  PubMed  PubMed Central  Google Scholar 

  30. Xu DZ, Wang XY, Shen XL, Gong GZ, Ren H, Guo LM, Sun AM, Xu M, Li LJ, Guo XH, Zhen Z, Wang HF, Gong HY, Xu C, Jiang N, Pan C, Gong ZJ, Zhang JM, Shang J, Xu J, Xie Q, Wu TF, Huang WX, Li YG, Xu J, Yuan ZH, Wang B, Zhao K, Wen YM; YIC Efficacy Trial Study Team. Results of a phase III clinical trial with an HBsAg-HBIG immunogenic complex therapeutic vaccine for chronic hepatitis B patients: experiences and findings. J Hepatol 2013; 59(3): 450–456

    Article  CAS  PubMed  Google Scholar 

  31. Bian Y, Zhang Z, Sun Z, Zhao J, Zhu D, Wang Y, Fu S, Guo J, Liu L, Su L, Wang FS, Fu YX, Peng H. Vaccines targeting PreS1 domain overcome immune tolerance in HBV carrier mice. Hepatology 2017; 66(4): 1067–1082

    Article  CAS  PubMed  Google Scholar 

  32. Wang X, Dong A, Xiao J, Zhou X, Mi H, Xu H, Zhang J, Wang B. Overcoming HBV immune tolerance to eliminate HBsAg-positive hepatocytes via pre-administration of GM-CSF as a novel adjuvant for a hepatitis B vaccine in HBV transgenic mice. Cell Mol Immunol 2016; 13(6): 850–861

    Article  CAS  PubMed  Google Scholar 

  33. Zhang TY, Yuan Q, Zhao JH, Zhang YL, Yuan LZ, Lan Y, Lo YC, Sun CP, Wu CR, Zhang JF, Zhang Y, Cao JL, Guo XR, Liu X, Mo XB, Luo WX, Cheng T, Chen YX, Tao MH, Shih JW, Zhao QJ, Zhang J, Chen PJ, Yuan YA, Xia NS. Prolonged suppression of HBV in mice by a novel antibody that targets a unique epitope on hepatitis B surface antigen. Gut 2016; 65(4): 658–671

    Article  CAS  PubMed  Google Scholar 

  34. Gao Y, Zhang TY, Yuan Q, Xia NS. Antibody-mediated immunotherapy against chronic hepatitis B virus infection. Hum Vaccin Immunother 2017:13(8): 1768–1773

    Article  PubMed  Google Scholar 

  35. Ren YD, Ye ZS, Yang LZ, Jin LX, Wei WJ, Deng YY, Chen XX, Xiao CX, Yu XF, Xu HZ, Xu LZ, Tang YN, Zhou F, Wang XL, Chen MY, Chen LG, Hong MZ, Ren JL, Pan JS. Fecal microbiota transplantation induces hepatitis B virus e-antigen (HBeAg) clearance in patients with positive HBeAg after long-term antiviral therapy. Hepatology 2017; 65(5): 1765–1768

    Article  PubMed  Google Scholar 

  36. Qin N, Yang F, Li A, Prifti E, Chen Y, Shao L, Guo J, Le Chatelier E, Yao J, Wu L, Zhou J, Ni S, Liu L, Pons N, Batto JM, Kennedy SP, Leonard P, Yuan C, Ding W, Chen Y, Hu X, Zheng B, Qian G, Xu W, Ehrlich SD, Zheng S, Li L. Alterations of the human gut microbiome in liver cirrhosis. Nature 2014; 513(7516): 59–64

    Article  CAS  PubMed  Google Scholar 

  37. Kang Y, Cai Y. Gut microbiota and hepatitis-B-virus-induced chronic liver disease: implications for faecal microbiota transplantation therapy. J Hosp Infect 2017; 96(4): 342–348

    Article  CAS  PubMed  Google Scholar 

  38. Zlotnick A, Venkatakrishnan B, Tan Z, Lewellyn E, Turner W, Francis S. Core protein: a pleiotropic keystone in the HBV lifecycle. Antiviral Res 2015; 121: 82–93

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Wu S, Zhao Q, Zhang P, Kulp J, Hu L, Hwang N, Zhang J, Block TM, Xu X, Du Y, Chang J, Guo JT. Discovery and mechanistic study of benzamide derivatives that modulate hepatitis B virus capsid assembly. J Virol 2017; 91(16): e00519–17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Yang L, Wang YJ, Chen HJ, Shi LP, Tong XK, Zhang YM, Wang GF, Wang WL, Feng CL, He PL, Xu YB, Lu MJ, Tang W, Nan FJ, Zuo JP. Effect of a hepatitis B virus inhibitor, NZ-4, on capsid formation. Antiviral Res 2016; 125: 25–33

    Article  CAS  PubMed  Google Scholar 

  41. Wang YJ, Lu D, Xu YB, Xing WQ, Tong XK, Wang GF, Feng CL, He PL, Yang L, Tang W, Hu YH, Zuo JP. A novel pyridazinone derivative inhibits hepatitis B virus replication by inducing genomefree capsid formation. Antimicrob Agents Chemother 2015; 59(11): 7061–7072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Tang L, Zhao Q, Wu S, Cheng J, Chang J, Guo JT. The current status and future directions of hepatitis B antiviral drug discovery. Expert Opin Drug Discov 2017; 12(1): 5–15

    Article  CAS  PubMed  Google Scholar 

  43. Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Infectious Diseases, Chinese Medical Association; Hou JL, Wei L. The guideline of prevention and treatment for chronic hepatitis B: a 2015 update. Chin J Hepatol (Zhonghua Gan Zang Bing Za Zhi) 2015; 23(12): 888–905 (in Chinese)

    Google Scholar 

  44. Qiu Z, Lin X, Zhou M, Liu Y, Zhu W, Chen W, Zhang W, Guo L, Liu H, Wu G, Huang M, Jiang M, Xu Z, Zhou Z, Qin N, Ren S, Qiu H, Zhong S, Zhang Y, Zhang Y, Wu X, Shi L, Shen F, Mao Y, Zhou X, Yang W, Wu JZ, Yang G, Mayweg AV, Shen HC, Tang G. Design and synthesis of orally bioavailable 4-methyl heteroaryldihydropyrimidine based hepatitis B virus (HBV) capsid inhibitors. J Med Chem 2016; 59(16): 7651–7666

    Article  CAS  PubMed  Google Scholar 

  45. Qiu Z, Lin X, Zhang W, Zhou M, Guo L, Kocer B, Wu G, Zhang Z, Liu H, Shi H, Kou B, Hu T, Hu Y, Huang M, Yan SF, Xu Z, Zhou Z, Qin N, Wang YF, Ren S, Qiu H, Zhang Y, Zhang Y, Wu X, Sun K, Zhong S, Xie J, Ottaviani G, Zhou Y, Zhu L, Tian X, Shi L, Shen F, Mao Y, Zhou X, Gao L, Young JAT, Wu JZ, Yang G, Mayweg AV, Shen HC, Tang G, Zhu W. Discovery and pre-clinical characterization of third-generation 4-H heteroaryldihydropyrimidine (HAP) analogues as hepatitis B virus (HBV) capsid inhibitors. J Med Chem 2017; 60(8): 3352–3371

    Article  CAS  PubMed  Google Scholar 

  46. Pei Y, Wang C, Yan SF, Liu G. Past, current, and future developments of therapeutic agents for treatment of chronic hepatitis B virus infection. J Med Chem 2017; 60(15): 6461–6479

    Article  CAS  PubMed  Google Scholar 

  47. Ren Q, Liu X, Luo Z, Li J, Wang C, Goldmann S, Zhang J, Zhang Y. Discovery of hepatitis B virus capsid assembly inhibitors leading to a heteroaryldihydropyrimidine based clinical candidate (GLS4). Bioorg Med Chem 2017; 25(3): 1042–1056

    Article  CAS  PubMed  Google Scholar 

  48. Chen J, Zhang W, Lin J, Wang F, Wu M, Chen C, Zheng Y, Peng X, Li J, Yuan Z. An efficient antiviral strategy for targeting hepatitis B virus genome using transcription activator-like effector nucleases. Mol Ther 2014; 22(2): 303–311

    Article  PubMed  Google Scholar 

  49. Liu X, Hao R, Chen S, Guo D, Chen Y. Inhibition of hepatitis B virus by the CRISPR/Cas9 system via targeting the conserved regions of the viral genome. J Gen Virol 2015; 96(8): 2252–2261

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  51. Wang J, Xu ZW, Liu S, Zhang RY, Ding SL, Xie XM, Long L, Chen XM, Zhuang H, Lu FM. Dual gRNAs guided CRISPR/Cas9 system inhibits hepatitis B virus replication. World J Gastroenterol 2015; 21(32): 9554–9565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Li H, Sheng C, Wang S, Yang L, Liang Y, Huang Y, Liu H, Li P, Yang C, Yang X, Jia L, Xie J, Wang L, Hao R, Du X, Xu D, Zhou J, Li M, Sun Y, Tong Y, Li Q, Qiu S, Song H. Removal of integrated hepatitis B virus DNA using CRISPR-Cas9. Front Cell Infect Microbiol 2017; 7: 91

    PubMed  PubMed Central  Google Scholar 

  53. Wang J, Chen R, Zhang R, Ding S, Zhang T, Yuan Q, Guan G, Chen X, Zhang T, Zhuang H, Nunes F, Block T, Liu S, Duan Z, Xia N, Xu Z, Lu F. The gRNA-miRNA-gRNA ternary cassette combining CRISPR/Cas9 with RNAi approach strongly inhibits hepatitis B virus replication. Theranostics 2017; 7(12): 3090–3105

    Article  PubMed  PubMed Central  Google Scholar 

  54. Zoulim F, Lebossé F, Levrero M. Current treatments for chronic hepatitis B virus infections. Curr Opin Virol 2016; 18: 109–116

    Article  CAS  PubMed  Google Scholar 

  55. Wang J, Shen T, Huang X, Kumar GR, Chen X, Zeng Z, Zhang R, Chen R, Li T, Zhang T, Yuan Q, Li PC, Huang Q, Colonno R, Jia J, Hou J, McCrae MA, Gao Z, Ren H, Xia N, Zhuang H, Lu F. Serum hepatitis B virus RNA is encapsidated pregenome RNA that may be associated with persistence of viral infection and rebound. J Hepatol 2016; 65(4): 700–710

    Article  CAS  PubMed  Google Scholar 

  56. Lu FM, Wang J, Chen XM, Jiang JN, Zhang WH, Zhao JM, Ren H, Hou JL, Xia NS. The potential use of serum HBV RNA to guide the functional cure of chronic hepatitis B. Chin J Hepatol (Zhonghua Gan Zang Bing Za Zhi) 2017; 25(2): 105–110 (in Chinese)

    CAS  Google Scholar 

  57. Li A, Yuan Q, Huang Z, Fan J, Guo R, Lou B, Zheng Q, Ge S, Chen Y, Su Z, Yeo AE, Chen Y, Zhang J, Xia N. Novel double-antigen sandwich immunoassay for human hepatitis B core antibody. Clin Vaccine Immunol 2010; 17(3): 464–469

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Song LW, Liu PG, Liu CJ, Zhang TY, Cheng XD, Wu HL, Yang HC, Hao XK, Yuan Q, Zhang J, Kao JH, Chen DS, Chen PJ, Xia NS. Quantitative hepatitis B core antibody levels in the natural history of hepatitis B virus infection. Clin Microbiol Infect 2015; 21(2): 197–203

    Article  CAS  PubMed  Google Scholar 

  59. Yuan Q, Song LW, Cavallone D, Moriconi F, Cherubini B, Colombatto P, Oliveri F, Coco BA, Ricco G, Bonino F, Shih JW, Xia NS, Brunetto MR. Total hepatitis B core antigen antibody, a quantitative non-invasive marker of hepatitis B virus induced liver disease. PLoS One 2015; 10(6): e0130209

    Article  PubMed  PubMed Central  Google Scholar 

  60. Fan R, Sun J, Yuan Q, Xie Q, Bai X, Ning Q, Cheng J, Yu Y, Niu J, Shi G, Wang H, Tan D, Wan M, Chen S, Xu M, Chen X, Tang H, Sheng J, Lu F, Jia J, Zhuang H, Xia N, Hou J; Chronic Hepatitis B Study Consortium. Baseline quantitative hepatitis B core antibody titre alone strongly predicts HBeAg seroconversion across chronic hepatitis B patients treated with peginterferon or nucleos(t)ide analogues. Gut 2016; 65(2): 313–320

    Article  CAS  PubMed  Google Scholar 

  61. Höner Zu Siederdissen C, Maasoumy B, Cornberg M. What is new on HBsAg and other diagnostic markers in HBV infection? Best Pract Res Clin Gastroenterol 2017; 31(3): 281–289

    Article  PubMed  Google Scholar 

  62. Chen EQ, Feng S, Wang ML, Liang LB, Zhou LY, Du LY, Yan LB, Tao CM, Tang H. Serum hepatitis B core-related antigen is a satisfactory surrogate marker of intrahepatic covalently closed circular DNA in chronic hepatitis B. Sci Rep 2017; 7(1): 173

    Article  PubMed  PubMed Central  Google Scholar 

  63. Wong DK, Seto WK, Cheung KS, Chong CK, Huang FY, Fung J, Lai CL, Yuen MF. Hepatitis B virus core-related antigen as a surrogate marker for covalently closed circular DNA. Liver Int 2017; 37(7): 995–1001

    Article  CAS  PubMed  Google Scholar 

  64. Song G, Yang R, Rao H, Feng B, Ma H, Jin Q, Wei L. Serum HBV core-related antigen is a good predictor for spontaneous HBeAg seroconversion in chronic hepatitis B patients. J Med Virol 2017; 89(3): 463–468

    Article  CAS  PubMed  Google Scholar 

  65. van Campenhout MJ, Brouwer WP, van Oord GW, Xie Q, Zhang Q, Zhang N, Guo S, Tabak F, Streinu-Cercel A, Wang J, Pas SD, Sonneveld MJ, de Knegt RJ, Boonstra A, Hansen BE, Janssen HL. Hepatitis B core-related antigen levels are associated with response to entecavir and peginterferon add-on therapy in hepatitis B e antigen-positive chronic hepatitis B patients. Clin Microbiol Infect 2016; 22(6): 571.e5–571.e9

    PubMed  Google Scholar 

  66. Ma H, Yang RF, Li XH, Jin Q, Wei L. HBcrAg identifies patients failing to achieve HBeAg seroconversion treated with pegylated interferon alfa-2b. Chin Med J (Engl) 2016; 129(18): 2212–2219

    Article  Google Scholar 

  67. Riveiro-Barciela M, Bes M, Rodríguez-Frías F, Tabernero D, Ruiz A, Casillas R, Vidal-González J, Homs M, Nieto L, Sauleda S, Esteban R, Buti M. Serum hepatitis B core-related antigen is more accurate than hepatitis B surface antigen to identify inactive carriers, regardless of hepatitis B virus genotype. Clin Microbiol Infect 2017 Mar 11 [Epub ahead of print] https://doi.org/10.1016/j. cmi.2017.03.003

    Google Scholar 

  68. Cheung KS, Seto WK, Wong DK, Lai CL, Yuen MF. Relationship between HBsAg, HBcrAg and hepatocellular carcinoma in patients with undetectable HBV DNA under nucleos(t)ide therapy. J Viral Hepat 2017; 24(8): 654–661

    Article  CAS  PubMed  Google Scholar 

  69. Zhang ZQ, Lu W, Wang YB, Weng QC, Zhang ZY, Yang ZQ, Feng YL. Measurement of the hepatitis B core-related antigen is valuable for predicting the pathological status of liver tissues in chronic hepatitis B patients. J Virol Methods 2016; 235: 92–98

    Article  CAS  PubMed  Google Scholar 

  70. Seto WK, Wong DH, Chan TY, Hwang YY, Fung J, Liu KS, Gill H, Lam YF, Cheung KS, Lie AK, Lai CL, Kwong YL, Yuen MF. Association of hepatitis B core-related antigen with hepatitis B virus reactivation in occult viral carriers undergoing high-risk immunosuppressive therapy. Am J Gastroenterol 2016; 111(12): 1788–1795

    Article  CAS  PubMed  Google Scholar 

  71. Chen G, Wang C, Chen J, Ji D, Wang Y, Wu V, Karlberg J, Lau G. Hepatitis B reactivation in hepatitis B and C coinfected patients treated with antiviral agents: a systematic review and meta-analysis. Hepatology 2017; 66(1): 13–26

    Article  CAS  PubMed  Google Scholar 

  72. Wang C, Ji D, Chen J, Shao Q, Li B, Liu J, Wu V, Wong A, Wang Y, Zhang X, Lu L, Wong C, Tsang S, Zhang Z, Sun J, Hou J, Chen G, Lau G. Hepatitis due to reactivation of hepatitis B virus in endemic areas among patients with hepatitis C treated with direct-acting antiviral agents. Clin Gastroenterol Hepatol 2017; 15(1): 132–136

    Article  PubMed  Google Scholar 

  73. Cheng X, Block P, Xia Y, Liang TJ. Hepatitis B virus replicates without being sensed by the innate immunity of the infected cells. 2016 International HBV Meeting. Sep 21–24, 2016, Seoul, Korea. Oral presentation abstract 119

    Google Scholar 

  74. Mutz P, Metz P, Lempp F, Bender S, Qu B, Schoneweis K, Restuccia A, Koschny R, Polychronidis G, Schemmer P, Baumert T, Urban S, Bartenschlager R. HBV bypasses the innate immune system and does not protect HCV against the antiviral effect of IFN. 2016 International HBV Meeting. Sep 21–24, 2016, Seoul, Korea. Oral presentation abstract 120

    Google Scholar 

  75. Sureau C, Negro F. The hepatitis delta virus: replication and pathogenesis. J Hepatol 2016; 64(1 Suppl): S102–S116

    Article  CAS  PubMed  Google Scholar 

  76. Lempp FA, Ni Y, Urban S. Hepatitis delta virus: insights into a peculiar pathogen and novel treatment options. Nat Rev Gastroenterol Hepatol 2016; 13(10): 580–589

    Article  CAS  PubMed  Google Scholar 

  77. Chen F, Zhang J, Guo F, Wen B, Luo S, Yuan D, Lin Y, Ou W, Tang P, Dai G, Li F, Liu W, Qu X. Hepatitis B, C, and D virus infection showing distinct patterns between injection drug users and the general population. J Gastroenterol Hepatol 2017; 32(2): 515–520

    Article  CAS  PubMed  Google Scholar 

  78. Liao B, Zhang F, Lin S, He H, Liu Y, Zhang J, Xu Y, Yi J, Chen Y, Liu H, Wang Z, Cai W. Epidemiological, clinical and histological characteristics of HBV/HDV co-infection: a retrospective crosssectional study in Guangdong, China. PLoS One 2014; 9(12): e115888

    Article  PubMed  PubMed Central  Google Scholar 

  79. Chen X, Oidovsambuu O, Liu P, Grosely R, Elazar M, Winn VD, Fram B, Boa Z, Dai H, Dashtseren B, Yagaanbuyant D, Genden Z, Dashdorj N, Bungert A, Dashdorj N, Glenn JS. A novel quantitative microarray antibody capture (Q-MAC) assay identifies an extremely high HDV prevalence amongst HBV infected Mongolians. Hepatology 2016 Nov 23. [Epub ahead of print] https://doi.org/10.1002/hep.28957

    Google Scholar 

  80. Wang X, Li M, Li S, Wu T, Zhang J, Xia N, Zhao Q. Prophylaxis against hepatitis E: at risk populations and human vaccines. Expert Rev Vaccines 2016; 15(7): 815–827

    Article  CAS  PubMed  Google Scholar 

  81. Zhu FC, Huang SJ, Wu T, Zhang XF, Wang ZZ, Ai X, Yan Q, Yang CL, Cai JP, Jiang HM, Wang YJ, Ng MH, Zhang J, Xia NS. Epidemiology of zoonotic hepatitis E: a community-based surveillance study in a rural population in China. PLoS One 2014; 9(1): e87154

    Article  PubMed  PubMed Central  Google Scholar 

  82. Zhang S, Chen C, Peng J, Li X, Zhang D, Yan J, Zhang Y, Lu C, Xun J, Li W, Ling Y, Huang Y, Chen L. Investigation of underlying comorbidities as risk factors for symptomatic human hepatitis E virus infection. Aliment Pharmacol Ther 2017; 45(5): 701–713

    Article  CAS  PubMed  Google Scholar 

  83. Shi Y, Yang Y, Hu Y, Wu W, Yang Q, Zheng M, Zhang S, Xu Z, Wu Y, Yan H, Chen Z. Acute-on-chronic liver failure precipitated by hepatic injury is distinct from that precipitated by extrahepatic insults. Hepatology 2015; 62(1): 232–242

    Article  PubMed  Google Scholar 

  84. Chen C, Zhang SY, Zhang DD, Li XY, Zhang YL, Li WX, Yan JJ, Wang M, Xun JN, Lu C, Ling Y, Huang YX, Chen L. Clinical features of acute hepatitis E super-infections on chronic hepatitis B. World J Gastroenterol 2016; 22(47): 10388–10397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Zhang F, Zhu H, Wu Y, Dou Z, Zhang Y, Kleinman N, Bulterys M, Wu Z, Ma Y, Zhao D, Liu X, Fang H, Liu J, Cai WP, Shang H. HIV, hepatitis B virus, and hepatitis C virus co-infection in patients in the China National Free Antiretroviral Treatment Program, 2010-12: a retrospective observational cohort study. Lancet Infect Dis 2014; 14(11): 1065–1072

    Article  PubMed  Google Scholar 

  86. Wu S, Yan P, Yang T, Wang Z, Yan Y. Epidemiological profile and risk factors of HIV and HBV/HCV co-infection in Fujian Province, southeastern China. J Med Virol 2017; 89(3): 443–449

    Article  CAS  PubMed  Google Scholar 

  87. Yang T, Chen Q, Li D, Wang T, Gou Y, Wei B, Tao C. High prevalence of syphilis, HBV and HCV co-infection, and low rate of effective vaccination against hepatitis B in HIV-infected patients in West China hospital. J Med Virol 2017 Aug 9. [Epub ahead of print] https://doi.org/10.1002/jmv.24912

    Google Scholar 

  88. Xie J, Han Y, Qiu Z, Li Y, Li Y, Song X, Wang H, Thio CL, Li T. Prevalence of hepatitis B and C viruses in HIV-positive patients in China: a cross-sectional study. J Int AIDS Soc 2016; 19(1): 20659

    Article  PubMed  PubMed Central  Google Scholar 

  89. Huang SM, Cai WP, Hu FY, Lan Y, Liao BL, Chen YP, Tang XP. Epidemiological and clinical characteristics of hepatitis B virus in HIV-infected patients in Guangdong, China. Int J STD AIDS 2016; 27(10): 890–897

    Article  CAS  PubMed  Google Scholar 

  90. Singh KP, Crane M, Audsley J, Avihingsanon A, Sasadeusz J, Lewin SR. HIV-hepatitis B virus coinfection: epidemiology, pathogenesis, and treatment. AIDS 2017; 31(15): 2035–2052

    Article  PubMed  Google Scholar 

  91. Li Y, Xie J, Han Y, Wang H, Zhu T, Wang N, Lv W, Guo F, Qiu Z, Li Y, Du S, Song X, Thio CL, Li T. Lamivudine monotherapy-based cART is efficacious for HBV treatment in HIV/HBV coinfection when baseline HBV DNA < 20, 000 IU/mL. J Acquir Immune Defic Syndr 2016; 72(1): 39–45

    Article  PubMed  PubMed Central  Google Scholar 

  92. Jiao Y, Li N, Chen X, Zhang T, Li H, Li W, Huang X, Liu Z, Zhang Y, Wu H. Acute HIV infection is beneficial for controlling chronic hepatitis B. Clin Infect Dis 2015; 60(1): 128–134

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This review was funded by the Major State Basic Research Development Program (No. 2015CB554300 to SZ) and the National Natural Science Foundation of China (No. 91442127 to ZZ). The authors also thank Ms. Jingjing Yan at the Shanghai Public Health Clinical Center for her assistance in preparing the figure.

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Authors and Affiliations

  1. Shanghai Public Health Clinical Center and Institute of Biomedical Sciences, Fudan University, Shanghai, 200032, China

    Shuye Zhang

  2. Department of Infectious Diseases, Beijing 302 Hospital, Beijing, 100039, China

    Fusheng Wang

  3. Research Center for Clinical & Translational Medicine, Beijiing 302 Hospital, Beijing, 100039, China

    Zheng Zhang

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  1. Shuye Zhang
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  2. Fusheng Wang
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  3. Zheng Zhang
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Correspondence to Zheng Zhang.

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Zhang, S., Wang, F. & Zhang, Z. Current advances in the elimination of hepatitis B in China by 2030. Front. Med. 11, 490–501 (2017). https://doi.org/10.1007/s11684-017-0598-4

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