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Prognosis, Prevention and Research Prospects of Progression to Severe Hepatitis B (Liver Failure)

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Book cover Acute Exacerbation of Chronic Hepatitis B

Abstract

This chapter describes the factors involved in the disease prognosis, parameters of outcome evaluations, principles and techniques for progression prevention. In last section, the future perspectives in both basic and clinical investigations towards unmet medical needs in AECHB and HBV ACLF are discussed.

  1. 1.

    Factors affecting the prognosis of patients with severe hepatitis B include those related to the virus (including viral load, HBeAg expression, and gene mutation), patient age, co-morbidity, TBil, INR, serum Cr, and the host genetic background. Indicators associated with patient prognosis include TBil, total cholesterol, albumin and prealbumin, hepatic encephalopathy, kidney damage, alpha-fetoprotein and vitamin D binding protein, blood sodium level, virus HBeAg expression and genotype, and blood glucose.

  2. 2.

    In addition to TBil, INR, hepatic encephalopathy, Cr level and AFP as indicators for prognosis of severe hepatitis, some other parameters such as clinical signs, symptoms, serum levels of total cholesterol and albumin and natrium, and coagulation factors are all valuable in assessment. The roles of cell apoptosis, liver regeneration and immunological parameters in assessing patient prognosis are under study. Prognostic evaluating systems include MELD score, MELD-Na score, iMELD score, KCI and CTP score.

  3. 3.

    Prevention of severe hepatitis B should be started in asymptomatic patients. Close observation, sufficient rest, adequate nutrition, meticulous nursing and psychological care, preventing and removing exacerbating factors, treating concomitant diseases, reasonable antiviral and comprehensive therapies are helpful to prevent CHB patients from developing to severe hepatitis. For patients who already have severe hepatitis B, the prevention and management of complications is important for lowering mortality rate.

  4. 4.

    New research directions in acute-on-chronic liver failure include: (1) Additional well controlled studies using present or new liver systems are warranted. Other approaches include the use of granulocyte colony stimulating factor to treat infections as well as the potential of use of stem cells to restore immune integrity and enhance liver regeneration. (2) Using new cell lines and animal models to understand the molecular biology of HBV, the immune response and to develop novel therapies. (3) Development of new anti-HBV strategies, e.g. silencing or remove cccDNA, enhancing immunologic clearance of HBV infection, inhibiting virus entry or HBc expression and using CRISP to disrupt cccDNA.

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References

  1. Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, Chinese Medical Association, Severe Liver Diseases and Artificial Liver Group, Chinese Society of Hepatology, Chinese Medical Association. Diagnostic and treatment guidelines for liver failure. Chin J Hepatol. 2006;14(9):643–6. (in Chinese).

    Google Scholar 

  2. Angeli P, Wong F, Watson H, et al. Hyponatremia in cirrhosis: results of a patient population survey. Hepatology. 2006;44(6):1535–42.

    CAS  PubMed  Google Scholar 

  3. Funk ML, Rosenberg DM, Lok AS. World-wide epidemiology of HBeAg-negative chronic hepatitis B and associated precore and core promoter variants. J Viral Hepat. 2002;9(1):52–61.

    CAS  PubMed  Google Scholar 

  4. Hou J, Schilling R, Janssen HLA, et al. Hepatitis B virus genotype a confer a higher response rate to interferon treatment. J Hepatol. 2001;34:15.

    Google Scholar 

  5. Kao JH, Wu NH, Chen PJ, et al. Hepatitis B genotypes and the response to interferon therapy. J Hepatol. 2000;33:998.

    CAS  PubMed  Google Scholar 

  6. Cui YL, Yan F, Wang YB, et al. Nucleoside analogue can improve the long-term prognosis of patients with hepatitis B virus infection-associated acute on chronic liver failure. Dig Dis Sci. 2010;55(8):2373–80.

    CAS  PubMed  Google Scholar 

  7. Lin J-S, et al. Meta analysis on prognostic factors of patients with severe hepatitis B. Chin J Exp Clin Infect Dis (Electronic Edition). 2011;5(1):14–9. https://doi.org/10.3877/cma.j.issn.1674-1358.2011.01.003. [Article in Chinese]

    Article  Google Scholar 

  8. Bernal W, Hall C, Karvellas CJ, et al. Arterial ammonia and clinical risk factors for encephalopathy and intracranial hypertension in acute liver failure. Hepatology. 2007;46(6):1844–52.

    CAS  PubMed  Google Scholar 

  9. Selcuk H, Uruc I, Temel MA, et al. Factors prognostic of survival in patients awaiting liver transplantation for end-stage liver disease. Dig Dis Sci. 2007;52(11):3217–23.

    PubMed  Google Scholar 

  10. Munoz SJ, Stravitz RT, Gabriel DA. Coagulopathy of acute liver failure. Clin Liver Dis. 2009;13:95–107.

    PubMed  Google Scholar 

  11. Wiesner RH, Freeman RB, Mulligan DC. Liver transplantation for hepatocellular cancer: the impact of the MELD allocation policy. Gastroenterology. 2004;127:S261–7.

    PubMed  Google Scholar 

  12. Malinchoc M, Kamath PS, Cordon FD, et al. A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology. 2000;31(4):864–71.

    CAS  PubMed  Google Scholar 

  13. Kamath PS, Wiesner RH, Malinchoc M, et al. A model to predict survival in patients with end-stage liver disease. Hepatology. 2001;33(2):464–70.

    CAS  PubMed  Google Scholar 

  14. McPhail MJ, Farne H, Senvar N, et al. Ability of King’s College Criteria and model for end-stage liver disease scores to predict mortality of patients with acute liver failure: a meta-analysis. Clin Gastroenterol Hepatol. 2016;14(4):516–25.

    PubMed  Google Scholar 

  15. Piotrowski D, Boroń-Kaczmarska A. Bacterial infections and hepatic encephalopathy in liver cirrhosis-prophylaxis and treatment. Adv Med Sci. 2017;62(2):345–56.

    PubMed  Google Scholar 

  16. Tian Z, Chen Y, Gao B. Natural killer cells in liver disease. Hepatology. 2013;57(4):1654–62.

    CAS  PubMed  Google Scholar 

  17. Häussinger D, Schliess F. Pathogenetic mechanisms of hepatic encephalopathy. Gut. 2008;57(8):1156–65.

    PubMed  Google Scholar 

  18. Hui CK, Leung N, Yuen ST, et al. Natural history and disease progression in Chinese chronic hepatitis B patients in immune-tolerant phase. Hepatology. 2007;46(2):395–401.

    PubMed  Google Scholar 

  19. European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370–98.

    Google Scholar 

  20. Freedman ND, Cross AJ, McGlynn KA, et al. Association of meat and fat intake with liver disease and hepatocellular carcinoma in the NIH-AARP cohort. J Natl Cancer Inst. 2010;102(17):1354–65.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Mota A, Guedes F, Areias J, et al. Alcohol consumption among patients with hepatitis B infection in northern Portugal considering gender and hepatitis B virus genotype differences. Alcohol. 2010;44(2):149–56.

    CAS  PubMed  Google Scholar 

  22. Sherman M, Llovet JM. Smoking, hepatitis B virus infection, and development of hepatocellular carcinoma. J Natl Cancer Inst. 2011;103(22):1642–3.

    PubMed  Google Scholar 

  23. Lin CW, Lin CC, Mo LR, et al. Heavy alcohol consumption increases the incidence of hepatocellular carcinoma in hepatitis B virus-related cirrhosis. J Hepatol. 2013;58(4):730–5.

    CAS  PubMed  Google Scholar 

  24. Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, CMA, Severe Liver Disease and Artificial Liver Group, Chinese Society of Hepatology, CMA. Chin J Clin Infect Dis. 2012;5(6):321–7.

    Google Scholar 

  25. Kim CH, Kallman JB, Bai C, et al. Nutritional assessments of patients with non-alcoholic fatty liver disease. Obes Surg. 2010;20(2):154–60.

    PubMed  Google Scholar 

  26. Nair S. Vitamin D deficiency and liver disease. Gastroenterol Hepatol. 2010;6(8):491–3.

    Google Scholar 

  27. Petta S, Cammd C, Scazzone C, et al. Low vitamin D serum level is related to severe fibrosis and low responsiveness to interferon-based therapy in genotype 1 chronic hepatitis C. Hepatology. 2010;51(4):1158–67.

    CAS  PubMed  Google Scholar 

  28. Yang YJ, Feng BY, Peng BW. Study on the effect of nursing intervention on chronic severe hepatitis and hepatic encephalopathy patient. Nurs Pract Res. 2011;8(12):17–9.

    CAS  Google Scholar 

  29. Chinese Society of Hepatology, Chinese Society of Infectious Diseases, Chinese Medical Association. The guideline of prevention and treatment for chronic hepatitis B (2010 version). Chin J Hepatol. 2011;19(1):13–24.

    Google Scholar 

  30. Gao S, Li D, Zha E, et al. Surveillance of hepatitis E virus contamination in shellfish in China. Int J Environ Res Public Health. 2015;12(2):2026–36.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Tang K, Li H, Li Q, et al. Retrospective study on the incidence and outcome of infection in patients with liver failure. J Chin Hepatol. 2007;10(2):109–11.

    Google Scholar 

  32. Khuroo MS, Khuroo MS, Khuroo NS. Transmission of hepatitis E virus in developing countries. Viruses. 2016;8(9):253.

    PubMed Central  Google Scholar 

  33. Aman W, Mousa S, Shiha G, et al. Current status and future directions in the management of chronic hepatitis C. Virol J. 2012;9:57.

    PubMed  PubMed Central  Google Scholar 

  34. Porepa L, Ray JG, Sanchez-Romeu P, et al. Newly diagnosed diabetes mellitus as a risk factor for serious liver disease. CMAJ. 2010;182(1):E526–31.

    PubMed  PubMed Central  Google Scholar 

  35. Saukkonen JJ, Cohn DL, Jasmer RM, et al. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med. 2006;174(8):935–52.

    CAS  PubMed  Google Scholar 

  36. Tostmann A, MJ B, Aamoutse RE, et al. Antituberculosis drug induced hepatotoxicity: concise up-to-date review. J Gastroenterol Hepatol. 2008;23(2):192–202.

    CAS  PubMed  Google Scholar 

  37. Marra F, Marra CA, Moadebi S, et al. Levofloxacin treatment of active tuberculosis and the risk of adverse events. Chest. 2005;128(3):1406–13.

    CAS  PubMed  Google Scholar 

  38. Koga K, Kawashima S, Shibata N, et al. Novel formulations of a liver protection drug glycyrrhizin. Yakugaku Zasshi. 2007;127(7):1103–14.

    CAS  PubMed  Google Scholar 

  39. Mayer KE, Myers RP, Lee SS. Silymarin treatment of viral hepatitis: a systematic review. J Viral Hepat. 2005;12(6):559–67.

    CAS  PubMed  Google Scholar 

  40. You J, Zhuang L, Cheng HY, et al. A randomized, controlled, clinical study of thymosin alpha-1 versus interferon-alpha in patients with chronic hepatitis B lacking HBeAg in China. J Chin Med Assoc. 2005;68(2):65–72.

    CAS  PubMed  Google Scholar 

  41. Liver Disease Committee, Chinese Association of Integrative Medicine. Guidelines for the diagnosis and treatment of liver fibrosis in integrative medicine practice. Chin J Hepatol. 2006;14(11):866–70.

    Google Scholar 

  42. Mpabanzi L, Jalan R. Neurological complications of acute liver failure: pathophysiological basis of current management and emerging therapies. Neurochem Int. 2012;60(7):736–42.

    CAS  PubMed  Google Scholar 

  43. Zhang Y, Liu W, Zhang FK. Recommendations on hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases. J Clin Hepatol. 2014;30(8):719–21.

    Google Scholar 

  44. Guevara M, Baccaro ME, Torre A, et al. Hyponatremia is a risk factor of hepatic encephalopathy in patients with cirrhosis: a prospective study with time-dependent analysis. Am J Gastroenterol. 2009;104(6):1382–9.

    PubMed  Google Scholar 

  45. Fernandez J, Navasa M, Planas R, et al. Primary prophylaxis of spontaneous bacterial peritonitis delays hepatorenal syndrome and improves survival in cirrhosis. Gastroenterology. 2007;133(3):818–24.

    CAS  PubMed  Google Scholar 

  46. Sort P, Navasa M, Arroyo V, et al. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med. 1999;341(6):403–9.

    CAS  PubMed  Google Scholar 

  47. Lee WM, Stravitz RT, Larson AM. Introduction to the revised American Association for the Study of Liver Diseases Position Paper on acute liver failure 2011. Hepatology. 2012;55(3):965–7.

    PubMed  Google Scholar 

  48. Italian Association for the Study of the Liver (AISF), Italian Society of Transfusion Medicine and Immunohaematology (SIMTI). AISF-SIMTI Position Paper: the appropriate use of albumin in patients with liver cirrhosis. Dig Liver Dis. 2016;48(1):4–15.

    Google Scholar 

  49. Angeli P, Ginès P, Wong F, et al. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. J Hepatol. 2015;62(4):968–74.

    PubMed  Google Scholar 

  50. Goldstein AL, Goldstein AL. From lab to bedside: emerging clinical applications of thymosin alpha 1. Expert Opin Biol Ther. 2009;9(5):593–608.

    CAS  PubMed  Google Scholar 

  51. Moreau R, Jalan R, Gines P, et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology. 2013;144:1426–37, 1437.e1–9.

    PubMed  Google Scholar 

  52. Jalan R. Novel approaches and therapeutics in acute-on-chronic liver failure. Liver Transpl. 2016;22:14–9.

    PubMed  Google Scholar 

  53. Jalan R, Pavesi M, Saliba F, et al. The CLIF Consortium Acute Decompensation score (CLIF-C ADs) for prognosis of hospitalised cirrhotic patients without acute-on-chronic liver failure. J Hepatol. 2015;62:831–40.

    PubMed  Google Scholar 

  54. Chisari FV, Isogawa M, Wieland SF. Pathogenesis of hepatitis B virus infection. Pathol Biol (Paris). 2010;58:258–66.

    CAS  Google Scholar 

  55. Wang X, Sarin SK, Ning Q. Definition of ACLF and inclusion criteria for extra-hepatic organ failure. Hepatol Int. 2015;9:360–5.

    PubMed  Google Scholar 

  56. Cheng Y, Guindon S, Rodrigo A, et al. Cumulative viral evolutionary changes in chronic hepatitis B virus infection precedes hepatitis B e antigen seroconversion. Gut. 2013;62:1347–55.

    PubMed  Google Scholar 

  57. Wang J, Ma K, Han M, et al. Nucleoside analogs prevent disease progression in HBV-related acute-on-chronic liver failure: validation of the TPPM model. Hepatol Int. 2014;8:64–71.

    CAS  PubMed  Google Scholar 

  58. Jalan R, Gines P, Olson JC, et al. Acute-on chronic liver failure. J Hepatol. 2012;57:1336–48.

    PubMed  Google Scholar 

  59. Herschorn S, Kaplan SA, Sun F, et al. Do patient characteristics predict responsiveness to treatment of overactive bladder with antimuscarinic agents? Urology. 2014;83:1023–9.

    PubMed  Google Scholar 

  60. Togel FE, Westenfelder C. Mesenchymal stem cells: a new therapeutic tool for AKI. Nat Rev Nephrol. 2010;6:179–83.

    PubMed  Google Scholar 

  61. Huebert RC, Rakela J. Cellular therapy for liver disease. Mayo Clin Proc. 2014;89:414–24.

    CAS  PubMed  Google Scholar 

  62. Shi M, Zhang Z, Xu R, et al. Human mesenchymal stem cell transfusion is safe and improves liver function in acute-on-chronic liver failure patients. Stem Cells Transl Med. 2012;1:725–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. King MA, Covassin L, Brehm MA, et al. Human peripheral blood leucocyte non-obese diabetic-severe combined immunodeficiency interleukin-2 receptor gamma chain gene mouse model of xenogeneic graft-versus-host-like disease and the role of host major histocompatibility complex. Clin Exp Immunol. 2009;157:104–18.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Schmidt MR, Appel MC, Giassi LJ, et al. Human BLyS facilitates engraftment of human PBL derived B cells in immunodeficient mice. PLoS One. 2008;3:e3192.

    PubMed  PubMed Central  Google Scholar 

  65. Habiro K, Sykes M, Yang YG. Induction of human T-cell tolerance to pig xenoantigens via thymus transplantation in mice with an established human immune system. Am J Transplant. 2009;9:1324–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Brehm MA, Shultz LD, Greiner DL. Humanized mouse models to study human diseases. Curr Opin Endocrinol Diabetes Obes. 2010;17:120–5.

    PubMed  PubMed Central  Google Scholar 

  67. McDermott SP, Eppert K, Lechman ER, et al. Comparison of human cord blood engraftment between immunocompromised mouse strains. Blood. 2010;116:193–200.

    CAS  PubMed  Google Scholar 

  68. Guidotti LG, Matzke B, Schaller H, et al. High-level hepatitis B virus replication in transgenic mice. J Virol. 1995;69:6158–69.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Gao S, Wang M, Ye H, et al. Dual interference with novel genes mfgl2 and mTNFR1 ameliorates murine hepatitis virus type 3-induced fulminant hepatitis in BALB/cJ mice. Hum Gene Ther. 2010;21:969–77.

    CAS  PubMed  Google Scholar 

  70. Brooks DG, Walsh KB, Elsaesser H, et al. IL-10 directly suppresses CD4 but not CD8 T cell effector and memory responses following acute viral infection. Proc Natl Acad Sci U S A. 2010;107:3018–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Brooks DG, Trifilo MJ, Edelmann KH, et al. Interleukin-10 determines viral clearance or persistence in vivo. Nat Med. 2006;12:1301–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Khattar R, Luft O, Yavorska N, et al. Targeted deletion of FGL2 leads to increased early viral replication and enhanced adaptive immunity in a murine model of acute viral hepatitis caused by LCMV WE. PLoS One. 2013;8:e72309.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Ma J, Huang C, Yao X, et al. Inhibition of hepatitis B virus and induction of hepatoma cell apoptosis by ASGPR-directed delivery of shRNAs. PLoS One. 2012;7:e46096.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Shalev I, Wong KM, Foerster K, et al. The novel CD4+CD25+ regulatory T cell effector molecule fibrinogen-like protein 2 contributes to the outcome of murine fulminant viral hepatitis. Hepatology. 2009;49:387–97.

    PubMed  Google Scholar 

  75. Guidotti LG, Rochford R, Chung J, et al. Viral clearance without destruction of infected cells during acute HBV infection. Science. 1999;284:825–9.

    CAS  PubMed  Google Scholar 

  76. Han M, Jiang J, Hou J, et al. Sustained immune control in HBeAg-positive patients who switched from entecavir therapy to pegylated interferon-alpha2a: 1 year follow-up of the OSST study. Antivir Ther. 2016;21:337–44.

    CAS  PubMed  Google Scholar 

  77. Fletcher SP, Delaney WET. New therapeutic targets and drugs for the treatment of chronic hepatitis B. Semin Liver Dis. 2013;33:130–7.

    CAS  PubMed  Google Scholar 

  78. Ramanan V, Shlomai A, Cox DB, et al. CRISPR/Cas9 cleavage of viral DNA efficiently suppresses hepatitis B virus. Sci Rep. 2015;5:10833.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Seeger C, Sohn JA. Complete spectrum of CRISPR/Cas9-induced mutations on HBV cccDNA. Mol Ther. 2016;24:1258–66.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Xi D, Wang M, Ye H, et al. Combined adenovirus-mediated artificial microRNAs targeting mfgl2, mFas, and mTNFR1 protect against fulminant hepatic failure in mice. PLoS One. 2013;8:e82330.

    PubMed  PubMed Central  Google Scholar 

  81. Lempp FA, Urban S. Inhibitors of hepatitis B virus attachment and entry. Intervirology. 2014;57:151–7.

    CAS  PubMed  Google Scholar 

  82. Ha SJ, Mueller SN, Wherry EJ, et al. Enhancing therapeutic vaccination by blocking PD-1-mediated inhibitory signals during chronic infection. J Exp Med. 2008;205:543–55.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Watanabe T, Bertoletti A, Tanoto TA. PD-1/PD-L1 pathway and T-cell exhaustion in chronic hepatitis virus infection. J Viral Hepat. 2010;17:453–8.

    CAS  PubMed  Google Scholar 

  84. Sun Y, Xi D, Ding W, et al. Soluble FGL2, a novel effector molecule of activated hepatic stellate cells, regulates T-cell function in cirrhotic patients with hepatocellular carcinoma. Hepatol Int. 2014;8:567–75.

    PubMed  Google Scholar 

  85. Ma Z, Zhang E, Yang D, et al. Contribution of Toll-like receptors to the control of hepatitis B virus infection by initiating antiviral innate responses and promoting specific adaptive immune responses. Cell Mol Immunol. 2015;12:273–82.

    CAS  PubMed  Google Scholar 

  86. Atkuri KR, Stevens JC, Neubert H. Mass cytometry: a highly multiplexed single-cell technology for advancing drug development. Drug Metab Dispos. 2015;43:227–33.

    PubMed  Google Scholar 

  87. Bandura DR, Baranov VI, Ornatsky OI, et al. Mass cytometry: technique for real time single cell multitarget immunoassay based on inductively coupled plasma time-of-flight mass spectrometry. Anal Chem. 2009;81:6813–22.

    CAS  PubMed  Google Scholar 

  88. Pope M, Marsden PA, Cole E, et al. Resistance to murine hepatitis virus strain 3 is dependent on production of nitric oxide. J Virol. 1998;72:7084–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Pope M, Rotstein O, Cole E, et al. Pattern of disease after murine hepatitis virus strain 3 infection correlates with macrophage activation and not viral replication. J Virol. 1995;69:5252–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Foerster K, Helmy A, Zhu Y, et al. The novel immunoregulatory molecule FGL2: a potential biomarker for severity of chronic hepatitis C virus infection. J Hepatol. 2010;53:608–15.

    CAS  PubMed  Google Scholar 

  91. Ferrari C, Missale G, Boni C, et al. Immunopathogenesis of hepatitis B. J Hepatol. 2003;39(Suppl 1):S36–42.

    CAS  PubMed  Google Scholar 

  92. Chang J, Guo JT. Treatment of chronic hepatitis B with pattern recognition receptor agonists: current status and potential for a cure. Antivir Res. 2015;121:152–9.

    CAS  PubMed  Google Scholar 

  93. Shim S, Kim J, Jung W, et al. Meta-analysis for genome-wide association studies using case-control design: application and practice. Epidemiol Health. 2016;38:e2016058.

    PubMed  PubMed Central  Google Scholar 

  94. Klumpp K, Lam AM, Lukacs C, et al. High-resolution crystal structure of a hepatitis B virus replication inhibitor bound to the viral core protein. Proc Natl Acad Sci U S A. 2015;112:15196–201.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Horvath P, Barrangou R. CRISPR/Cas, the immune system of bacteria and archaea. Science. 2010;327:167–70.

    CAS  PubMed  Google Scholar 

  96. Thirion M, Ochiya T. Roles of microRNAs in the hepatitis B virus infection and related diseases. Viruses. 2013;5:2690–703.

    PubMed  PubMed Central  Google Scholar 

  97. Lamontagne J, Steel LF, Bouchard MJ. Hepatitis B virus and microRNAs: complex interactions affecting hepatitis B virus replication and hepatitis B virus-associated diseases. World J Gastroenterol. 2015;21:7375–99.

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Zhao F, Xu G, Zhou Y, et al. MicroRNA-26b inhibits hepatitis B virus transcription and replication by targeting the host factor CHORDC1 protein. J Biol Chem. 2014;289:35029–41.

    PubMed  PubMed Central  Google Scholar 

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Wang, YM. et al. (2019). Prognosis, Prevention and Research Prospects of Progression to Severe Hepatitis B (Liver Failure). In: Ning, Q. (eds) Acute Exacerbation of Chronic Hepatitis B. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-1603-9_6

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