Study on the relationship between immune state and disease progression or disease severity of patients infected with hepatitis B virus_West China Medical Journal

Authors：

CHENZhu ,  ZENGYilan , WANGLi , HURong , WUBei , ZHULi , TANGYuzhen

Hepatitis Department, Public Health Clinical Center of Chengdu, Chengdu, Sichuan, 610066, P.R. China;

Corresponding?author：

ZENGYilan, Email: 277796360@qq.com

Keywords：

Hepatitis, type B; Immunoglobulin; Complement; T-lymphocyte subsets; Disease progression

DOI：

10.7507/1002-0179.201506109

Video：

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Objective To explore the relationship between immune state and disease progression or severity of patients with hepatitis B virus (HBV). Methods A total of 332 patients infected with HBV diagnosed and treated from January 2012 to December 2013 were divided into acute hepatitis B (AHB) group (n=25), chronic hepatitis B (CHB) group (n=237) and cirrhosis group (n=70) according to disease progression. Moreover, CHB group was divided into mild (n=24), moderate (n=103), serious (n=72) and severe group (liver failure group,n=38) according to disease severity, while cirrhosis group was divided into hepatocellular carcinoma (HCC) group (n=13) and non-HCC group (n=57). The immune indexes including immunoglobulin (Ig), complement (C) and T-lymphocyte subsets were tested and compared. Results The immune indexes were not significantly different between AHB group and CHB group (P>0.05). Compared with AHB group and CHB group, cirrhosis group had higher levels of IgG and IgA, and lower levels of CD3⁺, CD4⁺ and CD8⁺ T cells count (P<0.05). Compared with non-HCC group, HCC group had more male patients without antiviral therapy, who had higher levels of C3 and C4 (P<0.05). As disease progressed, the levels of alanine fcell couaminotransferase, aspartate aminotransferase, total cholesterol, Fibroscan index, IgG, and IgA of CHB patients all gradually increased, while the levels of C3 and C4 and the counts of CD3⁺ and CD4⁺ T cells gradually declined. Conclusions The immune state of patients infected with HBV has a certain relationship with disease progression or severity, and immunoglobulin, complement and T cells count can partly reflect the severity of the disease. Cirrhosis patients accompanied with high levels of C3 and C4 should pay high attention to antiviral therapy and be vigilant on HCC.

Citation： CHENZhu, ZENGYilan, WANGLi, HURong, WUBei, ZHULi, TANGYuzhen. Study on the relationship between immune state and disease progression or disease severity of patients infected with hepatitis B virus. West China Medical Journal, 2017, 32(1): 31-36. doi: 10.7507/1002-0179.201506109 Copy

1.	?Ganem D, Prince AM. Hepatitis B virus infection--natural history and clinical consequences. N Engl J Med, 2004, 350(11): 1118-1129.
2.	Rehermann B. Pathogenesis of chronic viral hepatitis: differential roles of T cell and NK cells. Nat Mesd, 2013, 19(7): 859-868.
3.	中華醫學會. 病毒性肝炎防治方案. 中華肝臟病雜志, 2000, 8(6): 324-329.
4.	中華醫學會肝病學分會, 中華醫學會感染病學分會. 慢性乙型肝炎防治指南(2010 年版). 臨床肝臟病雜志, 2011, 27(1): 1-16.
5.	中華醫學會感染病學分會肝衰竭與人工肝學組, 中華醫學會肝病學分會重型肝病與人工肝學組. 肝衰竭診治指南(2012 年版). 中華臨床感染病雜志, 2012, 5(6): 321-322.
6.	中華人民共和國衛生部. 原發性肝癌診療規范. 臨床腫瘤學雜志, 2011, 16(10): 929-946.
7.	孫煥煥, 張永宏. T 細胞在慢性乙型肝炎發病機制中的作用研究進展. 傳染病信息, 2014, 27(4): 237-239.
8.	楊晨辰, 黃睿, 劉勇, 等. 慢性 HBV 感染者不同免疫狀態下及抗病毒治療后外周血 T 細胞亞群比例和細胞因子水平特點. 中華實驗和臨床感染病雜志: 電子版, 2014, 8(2): 191-197.
9.	盛雄, 謝新生. 120 例乙型肝炎患者外周血 T 淋巴細胞亞群測定及意義. 中西醫結合肝病雜志, 2009, 19(1): 46-47.
10.	趙永曉, 馮麗英. CD8⁺CTL 在乙型肝炎發病作用中的研究現狀及進展. 世界華人消化雜志, 2009, 17(4): 384-388.
11.	張建春, 翁錫定, 陳孫云, 等. 乙型肝炎患者外周血 T 淋巴細胞亞群的變化. 實用肝臟病雜志, 2013, 16(4): 356-357.
12.	王琦. 免疫球蛋白血清檢測在肝病患者中的作用. 中國民康醫學, 2014, 26(1): 36-37.
13.	謝嬋, 謝俊強, 張宇鋒, 等. 抗病毒治療對慢性乙型肝炎患者免疫球蛋白及補體的影響. 中華傳染病雜志, 2012, 30(2): 100-104.
14.	Loggi E, Gamal N, Bihl F, et al. Adaptive response in hepatitis B virus infection. J Viral Hepat, 2014, 21(5): 305-313.
15.	Farci P, Diaz G, Chen Z, et al. B cell gene signature with massive intrahepatic production of antibodies to hepatitis B core antigen in hepatitis B virus-associated acute liver failure. Proc Natl Acad Sci USA, 2010, 107(19): 8766-8771.
16.	Abu-Amara M, Feld JJ. Does antiviral therapy for chronic hepatitis B reduce the risk of hepatocellular carcinoma?. Semin Liver Dis, 2013, 33(2): 157-166.
17.	唐宗生, 郝友華, 楊東亮. HBV 持續性感染中 T 細胞功能耗竭的機制研究進展. 中華肝臟病雜志, 2012, 20(11): 871-873.
18.	Lim YS, Kim WR. The global impact of hepatic fibrosis and endstage liver disease. Clin Liver Dis, 2008, 12(4): 733-746.
19.	王祖蓮, 曹向紅. 肝癌患者 31 例血清免疫球蛋白、補體的檢測及臨床意義. 中國社區醫師, 2013, 15(6): 267.
20.	Mi SP, Beom KK, Kyung SK, et al. Antiviral efficacies of currently available rescue therapies for multidrug-resistant chronic hepatitis B. Clin Mol Hepatol, 2013, 19(1): 29-35.
21.	陳潔, 張欣欣. 乙型肝炎病毒特征與肝硬化及原發性肝細胞癌關系的研究進展. 中華肝臟病雜志, 2014, 22(2): 153-155.
22.	王銘, 陳芳, 謝艷, 等. 人工肝治療乙型肝炎病毒相關慢加急性肝功能衰竭的短期預后影響因素分析. 華西醫學, 2016, 31(9): 1516-1520.
23.	龔非力. 醫學免疫學. 2 版. 北京: 科學出版社, 2004: 42-59.
24.	郭銀燕, 袁春蓓, 俞海英, 等. 慢性乙型肝炎與肝衰竭患兒外周血 T 淋巴細胞亞群的差異. 肝臟, 2014, 19(7): 514-517.
25.	陳智, 朱海紅, 楊英. 細胞因子風暴與肝衰竭. 臨床肝膽病雜志, 2014, 30(10): 981-983.
26.	Veiga-Parga T, Sehrawat S, Rouse BT. Role of regulatory T cells during virus infection. Immunol Rev, 2013, 255(1, SI): 182-196.
27.	Lau GK, Suri D, Liang R, et al. Resolution of chronic hepatitis B and anti-HBs seroconversion in humans by adoptive transfer of immunity to hepatitis B core antigen. Gastroenterology, 2002, 122(3): 614-624.
28.	王俊忠, 楊東亮. 免疫調節治療慢性乙型肝炎病毒感染的研究進展. 中華肝臟病雜志, 2015, 23(3): 227-230.
29.	Li F, Wei H, Wei H, et al. Blocking the natural killer cell inhibitory receptor NKG2A increases activity of human natural killer cells and clears hepatitis B virus infection in mice. Gastroenterology, 2013, 144(2): 392-401.
30.	喬艷, 徐東平, 李進, 等. 慢性乙型肝炎的免疫治療研究進展. 實用肝臟病雜志, 2016, 19(4): 493-496.

1. ?Ganem D, Prince AM. Hepatitis B virus infection--natural history and clinical consequences. N Engl J Med, 2004, 350(11): 1118-1129.
2. Rehermann B. Pathogenesis of chronic viral hepatitis: differential roles of T cell and NK cells. Nat Mesd, 2013, 19(7): 859-868.
3. 中華醫學會. 病毒性肝炎防治方案. 中華肝臟病雜志, 2000, 8(6): 324-329.
4. 中華醫學會肝病學分會, 中華醫學會感染病學分會. 慢性乙型肝炎防治指南(2010 年版). 臨床肝臟病雜志, 2011, 27(1): 1-16.
5. 中華醫學會感染病學分會肝衰竭與人工肝學組, 中華醫學會肝病學分會重型肝病與人工肝學組. 肝衰竭診治指南(2012 年版). 中華臨床感染病雜志, 2012, 5(6): 321-322.
6. 中華人民共和國衛生部. 原發性肝癌診療規范. 臨床腫瘤學雜志, 2011, 16(10): 929-946.
7. 孫煥煥, 張永宏. T 細胞在慢性乙型肝炎發病機制中的作用研究進展. 傳染病信息, 2014, 27(4): 237-239.
8. 楊晨辰, 黃睿, 劉勇, 等. 慢性 HBV 感染者不同免疫狀態下及抗病毒治療后外周血 T 細胞亞群比例和細胞因子水平特點. 中華實驗和臨床感染病雜志: 電子版, 2014, 8(2): 191-197.
9. 盛雄, 謝新生. 120 例乙型肝炎患者外周血 T 淋巴細胞亞群測定及意義. 中西醫結合肝病雜志, 2009, 19(1): 46-47.
10. 趙永曉, 馮麗英. CD8⁺CTL 在乙型肝炎發病作用中的研究現狀及進展. 世界華人消化雜志, 2009, 17(4): 384-388.
11. 張建春, 翁錫定, 陳孫云, 等. 乙型肝炎患者外周血 T 淋巴細胞亞群的變化. 實用肝臟病雜志, 2013, 16(4): 356-357.
12. 王琦. 免疫球蛋白血清檢測在肝病患者中的作用. 中國民康醫學, 2014, 26(1): 36-37.
13. 謝嬋, 謝俊強, 張宇鋒, 等. 抗病毒治療對慢性乙型肝炎患者免疫球蛋白及補體的影響. 中華傳染病雜志, 2012, 30(2): 100-104.
14. Loggi E, Gamal N, Bihl F, et al. Adaptive response in hepatitis B virus infection. J Viral Hepat, 2014, 21(5): 305-313.
15. Farci P, Diaz G, Chen Z, et al. B cell gene signature with massive intrahepatic production of antibodies to hepatitis B core antigen in hepatitis B virus-associated acute liver failure. Proc Natl Acad Sci USA, 2010, 107(19): 8766-8771.
16. Abu-Amara M, Feld JJ. Does antiviral therapy for chronic hepatitis B reduce the risk of hepatocellular carcinoma?. Semin Liver Dis, 2013, 33(2): 157-166.
17. 唐宗生, 郝友華, 楊東亮. HBV 持續性感染中 T 細胞功能耗竭的機制研究進展. 中華肝臟病雜志, 2012, 20(11): 871-873.
18. Lim YS, Kim WR. The global impact of hepatic fibrosis and endstage liver disease. Clin Liver Dis, 2008, 12(4): 733-746.
19. 王祖蓮, 曹向紅. 肝癌患者 31 例血清免疫球蛋白、補體的檢測及臨床意義. 中國社區醫師, 2013, 15(6): 267.
20. Mi SP, Beom KK, Kyung SK, et al. Antiviral efficacies of currently available rescue therapies for multidrug-resistant chronic hepatitis B. Clin Mol Hepatol, 2013, 19(1): 29-35.
21. 陳潔, 張欣欣. 乙型肝炎病毒特征與肝硬化及原發性肝細胞癌關系的研究進展. 中華肝臟病雜志, 2014, 22(2): 153-155.
22. 王銘, 陳芳, 謝艷, 等. 人工肝治療乙型肝炎病毒相關慢加急性肝功能衰竭的短期預后影響因素分析. 華西醫學, 2016, 31(9): 1516-1520.
23. 龔非力. 醫學免疫學. 2 版. 北京: 科學出版社, 2004: 42-59.
24. 郭銀燕, 袁春蓓, 俞海英, 等. 慢性乙型肝炎與肝衰竭患兒外周血 T 淋巴細胞亞群的差異. 肝臟, 2014, 19(7): 514-517.
25. 陳智, 朱海紅, 楊英. 細胞因子風暴與肝衰竭. 臨床肝膽病雜志, 2014, 30(10): 981-983.
26. Veiga-Parga T, Sehrawat S, Rouse BT. Role of regulatory T cells during virus infection. Immunol Rev, 2013, 255(1, SI): 182-196.
27. Lau GK, Suri D, Liang R, et al. Resolution of chronic hepatitis B and anti-HBs seroconversion in humans by adoptive transfer of immunity to hepatitis B core antigen. Gastroenterology, 2002, 122(3): 614-624.
28. 王俊忠, 楊東亮. 免疫調節治療慢性乙型肝炎病毒感染的研究進展. 中華肝臟病雜志, 2015, 23(3): 227-230.
29. Li F, Wei H, Wei H, et al. Blocking the natural killer cell inhibitory receptor NKG2A increases activity of human natural killer cells and clears hepatitis B virus infection in mice. Gastroenterology, 2013, 144(2): 392-401.
30. 喬艷, 徐東平, 李進, 等. 慢性乙型肝炎的免疫治療研究進展. 實用肝臟病雜志, 2016, 19(4): 493-496.

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