恩替卡韦治疗慢性乙型肝炎和乙型肝炎肝硬化患者血清和肝组织可溶性纤维蛋白原样蛋白2水平的变化

doi:10.3969/j.issn.1672-5069.2019.03.024

摘要/Abstract

摘要： 目的探讨应用恩替卡韦治疗的慢性乙型肝炎病毒感染者外周血和肝组织可溶性纤维蛋白原样蛋白2（sFGL2）水平的变化及其临床意义。方法 2016年6月~2017年6月我院收治的CHB患者112例和乙型肝炎肝硬化患者112例,其中CHB患者轻度38例,中度45例,重度29例。给予所有患者恩替卡韦治疗72周。常规行肝活检。采用ELISA法检测血清sFGL2水平,采用免疫组化法检测肝组织sFGL2表达。结果 CHB患者肝组织sFGL2阳性率为63.4%（71/112）,显著低于肝硬化患者的82.1%（92/112）,差异有统计学意义（P<0.05）;CHB患者肝组织sFGL2表达随病情程度加重而增强;治疗后,CHB患者血清ALT、AST和sFGL2水平分别（49.8±6.3） U/L、（52.3±7.6） U/L和（84.7±10.3）μg/L,而肝硬化患者则分别为（41.8±4.2） U/L、（42.3±5.4） U/L和（104.9±19.4）μg/L,差异显著（P<0.05）;在治疗24 w、48 w和72 w, CHB患者血清sFGL2水平分别为（98.2±10.8） μg/L、（81.6±9.5） μg/L和（69.4±8.7） μg/L,呈依次降低趋势;在治疗72 w末,完全应答65例,部分应答31例,无应答16例,其血清sFGL2水平分别为（74.6±9.1） μg/L、（97.2±11.4） μg/L和（123.6±15.2） μg/L,组间差异显著（P<0.05）。结论 CHB患者在抗病毒治疗后外周血和肝组织sFGL2水平降低显著,其与病情合应答反应关系密切,对病情评估和疗效预测可能具有重要的应用价值。

关键词: 肝硬化, 慢性乙型肝炎, 可溶性纤维蛋白原样蛋白2, 恩替卡韦, 治疗

Abstract: Objectiv To investigate the changes of serum and hepatic fibrinogen-like protein 2 （sFGL2） levels in patients with chronic hepatitis B（CHB） and hepatitis B cirrhosis after receiving entecavir therapy. Methods 112 patients with CHB and 112 patients with hepatitis B cirrhosis were admitted to our hospital between June 2016 and June 2017,and among patients with CHB were mild in 38 cases,moderate in 45 cases,and severe in 29 cases. All patients received liver biopsies and were given entecavir treatment for 72 weeks. Serum sFGL2 levels were assayed by ELISA,and hepatic sFGL2 expression was detected by immunohistochemistry. Results The positive rate of hepatic sFGL2 expression in patients with CHB was 63.4% （71/112）,much lower than 82.1% （92/112） in cirrhotic patients （P<0.05）;hepatic sFGL2 expression intensified as liver injuries increased in patients with CHB;at the end of 72 week observation,serum ALT,AST and sFGL2 levels in patients with CHB were （49.8±6.3） U/L,（52.3±7.6）U/L and （84.7±10.3） μg/L,while in patients with liver cirrhosis were （41.8±4.2）U/L,（42.3±5.4） U/L and（104.9±19.4） μg/L,respectively,and the difference was significant between the two groups （P<0.05）;at the end of 24 w,48 w and 72 w,serum sFGL2 level in patients with CHB were（98.2±10.8） μg/L,（81.6±9.5） μg/L and （69.4±8.7） μg/L,in a gradually decreased manner;at the end of 72 w,65 patients with CHB got complete response,31 got partial response and 16 were non-responders,and their serum sFGL2 levels were （74.6±9.1） μg/L,（97.2±11.4） μg/L and（123.6±15.2） μg/L,respectively,with the differences among the three groups significant（P<0.05）. Conclusion Serum and hepatic sFGL2 levels in patients with CHB significantly decrease after antiviral therapy,which might be closely related to the state of disease activity and the response to treatment.

Key words: Liver cirrhosis, Hepatitis B, Soluble fibrinogen-like protein 2, Entecavir, Therapy

谷孙泽栋, 杨晓飞, 张佩欣. 恩替卡韦治疗慢性乙型肝炎和乙型肝炎肝硬化患者血清和肝组织可溶性纤维蛋白原样蛋白2水平的变化[J]. 实用肝脏病杂志, 2019, 22(3): 405-408.

Gu Sunzedong, Yang Xiaofei, Zhang Peixin. Changes of serum and hepatic fibrinogen-like protein 2 levels in patients with chronic hepatitis B and hepatitis B cirrhosis after receiving entecavir therapy[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2019, 22(3): 405-408.

参考文献

[1] Li X,Zhou L,Gu L,et al.Veritable antiviral capacity of natural killer cells in chronic HBV infection:an argument for an earlier anti-virus treatment. J Transl Med,2017,15(1):220.
[2] Jin K,Rui Y,Yamamoto T,et al.Human neutrophil elastase induce interleukin-10 expression in peripheral blood mononuclear cells through protein kinase C Theta/Delta and phospholipase pathways. Cell J,2016,17(4):692-700.
[3] Cheng J,Chen Y,Xu B,et al.Association of soluble fibrinogen-like protein 2 with the severity of coronary artery disease. Intern Med,2016,55(17):2343-2350.
[4] 肖玉柱. 柴胡解毒汤联合阿德福韦酯治疗慢性乙型肝炎患者外周血淋巴细胞亚群和细胞因子的变化. 实用肝脏病杂志,2017,20(1):34-37.
[5] Bartczak A,Chruscinski A,Mendicino M,et al.Overexpression of fibrinogen-like protein 2 promotes tolerance in a fully mismatched murine model of heart transplantation. Am J Transplant,2016,16(6):1739-1750.
[6] Xue JM,Yang LT,Yang G,et al.Protease-activated receptor-2 suppresses interleukin(IL)-10 expression in B cells via up regulating Bcl2L12 in patients with allergic rhinitis. Allergy,2017,72(11):1704-1712.
[7] Sheikh AA,Aggarwal A,Aarif O.Effect of in vitro zinc supplementation on HSPs expression and interleukin 10 production in heat treated peripheral blood mononuclear cells of transition Sahiwal and Karan fries cows. J Therm Biol,2016,56(1):68-76.
[8] 谢东京,黄煌,周新元. FGL2在急性病毒感染过程中对T细胞免疫应答的影响研究. 免疫学杂志,2017,33(3):197-202.
[9] Yu SL,Deng H,Li XH,et al.Expression of microRNA-155 is downregulated in peripheral blood mononuclear cells of chronic hepatitis B patients. Hepat Mon,2016,16(1):e34483.
[10] Hu C.Stroma-derived fibrinogen-like protein 2 activates cancer-associated fibroblasts to promote tumor growth in lung cancer. Int J Biol Sci,2017,13(6):804-814.
[11] Klingberg O,Khattar R,Farrokhi K,et al.Inhibition of the FGL2:FcγRIIB/RIII immunosuppressive pathway enhances antiviral T cell and B cell responses leading to clearance of LCMV cl-13. Immunology,2018,154(3):476-489.
[12] 李田军,马辉. 恩替卡韦联合胸腺素α1治疗慢性乙型肝炎患者疗效及其外周血T淋巴细胞亚群的变化. 实用肝脏病杂志, 2018,21(3):455-456.
[13] Etesam Z,Nemati M,Ebrahimizadeh MA,et al.Altered expression of specific transcription factors of Th17 (RORγt,RORα) and Treg lymphocytes(FOXP3) by peripheral blood mononuclear cells from patients with multiple sclerosis. J Mol Neurosci,2016,60(1):1-8.
[14] Boni C,Vecchi A,Rossi M,et al.TLR7 agonist increases responses of HBV-specific T cells and natural killer cells in patients with chronic hepatitis B treated with nucleos(t)ide analogues. Gastroenterology,2018,154(6):1764-1777.
[15] Yuan B,Huang S,Gong S,et al.Programmed death (PD)-1 attenuates macrophage activation and brain inflammation via regulation of fibrinogen-like protein 2(Fgl-2) after intracerebral hemorrhage in mice.Immunol Lett,2016,179(1):114-121.
[16] Wang M,Liu J,Xi D,et al.Adenovirus-mediated artificial microRNA against human fibrinogen like protein 2 inhibits hepatocellular carcinoma growth. J Gene Med,2016,18(7):102-111.
[17] Elmesery M,Elmowafy M,Elgaml A,et al.Correlation of serum soluble fibrinogen-like protein 2 with soluble FAS ligand and interferon gamma in Egyptian hepatitis C virus-infected patients and hepatocellular carcinoma patients. J Interferon Cytokine Res,2017,37(8):342-347.
[18] Fan YC,Zhang YY,Sun YY,et al.Altered expression of A20 gene in peripheral blood mononuclear cells is associated with the progression of chronic hepatitis B virus infection. Oncotarget,2016,7(42):68821-68832.
[19] Wong GL,Seto WK,Wong VW,et al.Long-term safety of oral anti-viral treatment for chronic hepatitis B. Aliment Pharmacol Ther,2018,47(6):730-737.
[20] Yu H, Liu Y,Huang J,et al.IL-33 protects murine viral fulminant hepatitis by targeting coagulation hallmark protein FGL2/fibroleukin expression. Mol Immunol,2017,87(1):171-179.