Frontiers of Medicine

, Volume 11, Issue 4, pp 490–501 | Cite as

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

Review
First Online:
Received:
Accepted:
  • 113 Downloads

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.

Keywords

HBV CHB biomarker functional cure coinfection 
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Notes

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.

References

  1. 1.
    World Health Organizaiton. Global Hepatitis Report 2017. 2017:3Google Scholar
  2. 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. 3.
    Liao X, Liang Z. Strategy vaccination against Hepatitis B in China. Hum Vaccin Immunother 2015; 11(6): 1534–1539PubMedPubMedCentralGoogle Scholar
  4. 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–J14CrossRefPubMedGoogle Scholar
  5. 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): 52–56CrossRefPubMedGoogle Scholar
  6. 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): 39–47CrossRefPubMedGoogle Scholar
  7. 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): 6550–6557CrossRefPubMedGoogle Scholar
  8. 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): 765–772CrossRefPubMedPubMedCentralGoogle Scholar
  9. 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): e1001774CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Zhuang H. Several issues regarding prevention of mother-to-child transmission of hepatitis B virus. J Clin Hepatol 2016; 32: 2227–2230Google Scholar
  11. 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–e25CrossRefPubMedGoogle Scholar
  12. 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: 32–39CrossRefPubMedGoogle Scholar
  13. 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): 2324–2334CrossRefPubMedGoogle Scholar
  14. 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): 1103–1105CrossRefPubMedGoogle Scholar
  15. 15.
    Yu R, Fan R, Hou J. Chronic hepatitis B virus infection: epidemiology, prevention, and treatment in China. Front Med 2014; 8(2): 135–144CrossRefPubMedGoogle Scholar
  16. 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): 618–623CrossRefPubMedGoogle Scholar
  17. 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): 1283–1292CrossRefPubMedGoogle Scholar
  18. 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): 337–344CrossRefPubMedGoogle Scholar
  19. 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): 777–784CrossRefPubMedGoogle Scholar
  20. 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. 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): 1512–1522CrossRefPubMedGoogle Scholar
  22. 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. 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): 177–188CrossRefPubMedGoogle Scholar
  24. 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): 1058–1066CrossRefPubMedGoogle Scholar
  25. 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): 674–682CrossRefPubMedGoogle Scholar
  26. 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): 1–98CrossRefPubMedGoogle Scholar
  27. 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): 1893–1908CrossRefPubMedPubMedCentralGoogle Scholar
  28. 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): 986–997CrossRefPubMedPubMedCentralGoogle Scholar
  29. 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): e2565CrossRefPubMedPubMedCentralGoogle Scholar
  30. 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): 450–456CrossRefPubMedGoogle Scholar
  31. 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): 1067–1082CrossRefPubMedGoogle Scholar
  32. 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): 850–861CrossRefPubMedGoogle Scholar
  33. 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): 658–671CrossRefPubMedGoogle Scholar
  34. 34.
    Gao Y, Zhang TY, Yuan Q, Xia NS. Antibody-mediated immunotherapy against chronic hepatitis B virus infection. Hum Vaccin Immunother 2017:13(8): 1768–1773CrossRefPubMedGoogle Scholar
  35. 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): 1765–1768CrossRefPubMedGoogle Scholar
  36. 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): 59–64CrossRefPubMedGoogle Scholar
  37. 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): 342–348CrossRefPubMedGoogle Scholar
  38. 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: 82–93CrossRefPubMedPubMedCentralGoogle Scholar
  39. 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): e00519–17CrossRefPubMedPubMedCentralGoogle Scholar
  40. 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: 25–33CrossRefPubMedGoogle Scholar
  41. 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): 7061–7072CrossRefPubMedPubMedCentralGoogle Scholar
  42. 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): 5–15CrossRefPubMedGoogle Scholar
  43. 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. 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): 7651–7666CrossRefPubMedGoogle Scholar
  45. 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): 3352–3371CrossRefPubMedGoogle Scholar
  46. 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): 6461–6479CrossRefPubMedGoogle Scholar
  47. 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): 1042–1056CrossRefPubMedGoogle Scholar
  48. 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): 303–311CrossRefPubMedGoogle Scholar
  49. 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): 2252–2261CrossRefPubMedGoogle Scholar
  50. 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: 110–117CrossRefPubMedGoogle Scholar
  51. 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): 9554–9565CrossRefPubMedPubMedCentralGoogle Scholar
  52. 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: 91PubMedPubMedCentralGoogle Scholar
  53. 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): 3090–3105CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Zoulim F, Lebossé F, Levrero M. Current treatments for chronic hepatitis B virus infections. Curr Opin Virol 2016; 18: 109–116CrossRefPubMedGoogle Scholar
  55. 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): 700–710CrossRefPubMedGoogle Scholar
  56. 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)Google Scholar
  57. 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): 464–469CrossRefPubMedPubMedCentralGoogle Scholar
  58. 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): 197–203CrossRefPubMedGoogle Scholar
  59. 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): e0130209CrossRefPubMedPubMedCentralGoogle Scholar
  60. 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): 313–320CrossRefPubMedGoogle Scholar
  61. 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): 281–289CrossRefPubMedGoogle Scholar
  62. 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): 173CrossRefPubMedPubMedCentralGoogle Scholar
  63. 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): 995–1001CrossRefPubMedGoogle Scholar
  64. 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): 463–468CrossRefPubMedGoogle Scholar
  65. 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.e9PubMedGoogle Scholar
  66. 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): 2212–2219CrossRefGoogle Scholar
  67. 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.2017.03.003Google Scholar
  68. 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): 654–661CrossRefPubMedGoogle Scholar
  69. 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: 92–98CrossRefPubMedGoogle Scholar
  70. 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): 1788–1795CrossRefPubMedGoogle Scholar
  71. 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): 13–26CrossRefPubMedGoogle Scholar
  72. 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): 132–136CrossRefPubMedGoogle Scholar
  73. 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 119Google Scholar
  74. 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 120Google Scholar
  75. 75.
    Sureau C, Negro F. The hepatitis delta virus: replication and pathogenesis. J Hepatol 2016; 64(1 Suppl): S102–S116CrossRefPubMedGoogle Scholar
  76. 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): 580–589CrossRefPubMedGoogle Scholar
  77. 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): 515–520CrossRefPubMedGoogle Scholar
  78. 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): e115888CrossRefPubMedPubMedCentralGoogle Scholar
  79. 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.28957Google Scholar
  80. 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): 815–827CrossRefPubMedGoogle Scholar
  81. 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): e87154CrossRefPubMedPubMedCentralGoogle Scholar
  82. 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): 701–713CrossRefPubMedGoogle Scholar
  83. 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): 232–242CrossRefPubMedGoogle Scholar
  84. 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): 10388–10397CrossRefPubMedPubMedCentralGoogle Scholar
  85. 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): 1065–1072CrossRefPubMedGoogle Scholar
  86. 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): 443–449CrossRefPubMedGoogle Scholar
  87. 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.24912Google Scholar
  88. 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): 20659CrossRefPubMedPubMedCentralGoogle Scholar
  89. 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): 890–897CrossRefPubMedGoogle Scholar
  90. 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): 2035–2052CrossRefPubMedGoogle Scholar
  91. 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): 39–45CrossRefPubMedPubMedCentralGoogle Scholar
  92. 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): 128–134CrossRefPubMedGoogle Scholar

Copyright information

© Higher Education Press and Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Shanghai Public Health Clinical Center and Institute of Biomedical SciencesFudan UniversityShanghaiChina
  2. 2.Department of Infectious DiseasesBeijing 302 HospitalBeijingChina
  3. 3.Research Center for Clinical & Translational MedicineBeijiing 302 HospitalBeijingChina

Personalised recommendations