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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 35 Issue 8
Aug.  2019
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Article Contents

Research advances in the diagnosis and treatment of patients in the immune tolerance stage of chronic hepatitis B virus infection

DOI: 10.3969/j.issn.1001-5256.2019.08.039
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  • Received Date: 2019-05-27
  • Published Date: 2019-08-20
  • Patients in the immune tolerance stage of chronic hepatitis B virus (HBV) infection are in a state of high viral replication and low inflammation in the liver, and they often have no disease progression. Therefore, antiviral therapy is not recommended in related guidelines.Recent studies have found that the patients in the immune tolerance stage have immune response and liver injury, which is a risk factor for liver cancer, and therefore, antiviral therapy should be actively initiated to prevent disease progression. This article summarizes the research advances in the diagnosis and treatment of patients in the immune tolerance stage of chronic HBV infection and points out that there are still controversies over the application of antiviral therapy in such patients. Appropriate timing of antiviral therapy has a great significance in improving patients' prognosis and reducing their economic burden.

     

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  • [1] DING Y, DOU XG. Antiviral therapeutic strategies for chronic hepatitis B patients with a normal alanine aminotransferase level[J]. J Clin Hepatol, 2018, 34 (5) :926-929. (in Chinese) 丁洋, 窦晓光. ALT正常的慢性乙型肝炎抗病毒治疗策略[J].临床肝胆病杂志, 2018, 34 (5) :926-929.
    [2] KENNEDY PTF, LITWIN S, DOLMAN GE, et al. Immune tolerant chronic hepatitis B:The unrecognized risks[J]. Viruses, 2017, 9 (5) :96.
    [3] WONG GL. Management of chronic hepatitis B patients in immunetolerant phase:What latest guidelines recommend[J].Clin Mol Hepatol, 2018, 24 (2) :108-113.
    [4] European Association for the Study of the Liver. EASL 2017clinical practice guidelines on the management of hepatitis B virus infection[J]. J Hepatol, 2017, 67 (2) :370-398.
    [5] SARIN SK, KUMAR M, LAU GK, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B:A 2015update[J]. Hepatol Int, 2016, 10 (1) :1-98.
    [6] TERRAULT NA, LOK ASF, McMAHON BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B:AASLD 2018 hepatitis B guidance[J]. Hepatology, 2018, 67 (4) :1560-1599.
    [7] Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association. The guideline of prevention and treatment for chronic hepatitis B:A 2015 update[J]. J Clin Hepatol, 2015, 31 (12) :1941-1960. (in Chinese) 中华医学会肝病学分会, 中华医学会感染病学分会.慢性乙型肝炎防治指南 (2015年更新版) [J].临床肝胆病杂志, 2015, 31 (12) :1941-1960.
    [8] ANDREANI T, SERFATY L, MOHAND D, et al. Chronic hepatitis B virus carriers in the immunotolerant phase of infection:Histologic findings and outcome[J]. Clin Gastroenterol Hepatol, 2007, 5 (5) :636-641.
    [9] HUI CK, LEUNG N, YUEN ST, et al. Natural history and disease progression in Chinese chronic hepatitis B patients in immune-tolerant phase[J]. Hepatology, 2007, 46 (2) :395-401.
    [10] YAPALI S, TALAAT N, FONTANA RJ, et al. Outcomes of patients with chronic hepatitis B who do not meet criteria for antiviral treatment at presentation[J]. Clin Gastroenterol Hepatol, 2015, 13 (1) :193-201.
    [11] CHAN HL, CHAN CK, HUI AJ, et al. Effects of tenofovir disoproxil fumarate in hepatitis B e antigen-positive patients with normal levels of alanine aminotransferase and high levels of hepatitis B virus DNA[J]. Gastroenterology, 2014, 146 (5) :1240-1248.
    [12] PERRILLO RP, LAI CL, LIAW YF, et al. Predictors of HBe Ag loss after lamivudine treatment for chronic hepatitis B[J].Hepatology, 2002, 36 (1) :186-194.
    [13] FELD JJ, TERRAULT NA, LIN HS, et al. Entecavir and peginterferon alfa-2a in adults with hepatitis B e antigenpositive immune-tolerant chronic hepatitis B virus infection[J]. Hepatology, 2019, 69 (6) :2338-2348.
    [14] GUIDOTTI L, INVERSO D, SIRONI L, et al. Immunosurveillance of the liver by intravascular effector CD8+T cells[J].Cell, 2015, 161 (3) :486-500.
    [15] FIORAVANTI J, DI LUCIA P, MAGINI D, et al. Effector CD8+T cell-derived interleukin-10 enhances acute liver immunopathology[J]. J Hepatol, 2017, 67 (3) :543-548.
    [16] MASON WS, GILL US, LITWIN S, et al. HBV DNA integration and clonal hepatocyte expansion in chronic hepatitis B patients considered immune tolerant[J]. Gastroenterology, 2016, 151 (5) :986-998.
    [17] KENNEDY PTF, SANDALOVA E, JO J, et al. Preserved Tcell function in children and young adults with immune-tolerant chronic hepatitis B[J]. Gastroenterology, 2012, 143 (3) :637-645.
    [18] GAO HY, LIU N, LI CX, et al. Clinical features and liver histopathology of patients in the immune tolerance stage of chronic hepatitis B virus infection[J]. Chin Hepatol, 2018, 23 (2) :136-139. (in Chinese) 高红艳, 刘娜, 李春霞, 等.慢性乙型肝炎病毒感染者免疫耐受期的临床特征与肝组织病理学分析[J].肝脏, 2018, 23 (2) :136-139.
    [19] XING YF, ZHOU DQ, HE JS, et al. Clinical and histopathological features of chronic hepatitis B virus infected patients with high HBV-DNA viral load and normal alanine aminotransferase level:A multicentre-based study in China[J]. PLo S One, 2018, 13 (9) :e0203220.
    [20] WONG GL, CHAN HL, YU Z, et al. Liver fibrosis progression in chronic hepatitis B patients positive for hepatitis B e antigen:A prospective cohort study with paired transient elastography examination[J]. J Gastroenterol Hepatol, 2013, 28 (11) :1762-1769.
    [21] ZHANG HF, ZHU SS, YANG XJ, et al. Clinical manifestations and pathological changes of hepatitis B and C in children[J].Infect Dis Info, 2006, 19 (3) :130-131, 141. (in Chinese) 张鸿飞, 朱世殊, 杨晓晋, 等.小儿乙、丙型肝炎临床与病理研究[J].传染病信息, 2006, 19 (3) :130-131, 141.
    [22] CHEN CJ, YANG HI, SU J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level[J]. JAMA, 2006, 295 (1) :65-73.
    [23] SHEN J, LIU J, LI C, et al. The prognostic significance of serum HBe Ag on the recurrence and long-term survival after hepatectomy for hepatocellular carcinoma:A propensity score matching analysis[J]. J Viral Hepat, 2018, 25 (9) :1057-1065.
    [24] ZHOU TC, LAI X, FENG HM, et al. Systematic review and meta-analysis:Development of hepatocellular carcinoma in chronic hepatitis B patients with hepatitis e antigen seroconversion[J]. J Viral Hepat, 2018, 25 (10) :1172-1179.
    [25] KIM GA, LIM YS, HAN S, et al. High risk of hepatocellular carcinoma and death in patients with immune-tolerantphase chronic hepatitis B[J]. Gut, 2018, 67 (5) :945-952.
    [26] ZHANG S, MA Q, LIANG S, et al. Annual economic burden of hepatitis B virus-related diseases among hospitalized patients in twelve cities in China[J]. J Viral Hepat, 2016, 23 (3) :202-210.
    [27] CHANG Y, CHOE WH, SINN DH, et al. Nucleos (t) ide analogue treatment for patients with hepatitis B virus (HBV) e antigen-positive chronic HBV genotype C infection:A nationwide, multicenter, retrospective study[J]. J Infect Dis, 2017, 216 (11) :1407-1414.
    [28] LIU ZH. Timing of antiviral therapy for chronic HBV infection patients with normal alanine aminotransferase and positive HBV DNA[D]. Nanning:Guangxi Medical University, 2015. (in Chinese) 刘志红. ALT正常HBV DNA阳性的慢性HBV感染者抗病毒治疗时机的探讨[D].南宁:广西医科大学, 2015.
    [29] ZHU S, ZHANG H, DONG Y, et al. Antiviral therapy in hepatitis B virus-infected children with immune-tolerant characteristics:A pilot open-label randomized study[J]. J Hepatol, 2018, 68 (6) :1123-1128.
    [30] BERTOLETTI A, KENNEDY PT. The immune tolerant phase of chronic HBV infection:New perspectives on an old concept[J]. Cell Mol Immunol, 2015, 12 (3) :258-263.
    [31] PROTZER U, KNOLLE P.“To Be or Not to Be”:Immune tolerance in chronic hepatitis B[J]. Gastroenterology, 2016, 151 (5) :805-806.
    [32] VISVANATHAN K, DUSHEIKO G, GILES M, et al. Managing HBV in pregnancy. Prevention, prophylaxis, treatment and follow-up:Position paper produced by Australian, UK and New Zealand key opinion leaders[J]. Gut, 2016, 65 (2) :340-350.
    [33] VLACHOGIANNAKOS J, PAPATHEODORIDIS GV. HBV:Do I treat my immunotolerant patients?[J]. Liver Int, 2016, 36 (Suppl 1) :93-99.
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