血清白细胞介素-37在乙型肝炎病毒相关慢加急性肝衰竭患者中的变化及其临床意义
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摘要
目的探讨血清白细胞介素-37(IL-37)在乙型肝炎病毒相关的慢加急性肝衰竭(HBV-ACLF)患者中的变化特点及其临床意义。方法选择2015年6月—2017年6月我科收治的HBV-ACLF的患者81例(HBV-ACLB组),其中早期25例、中期32例、晚期24例。同时纳入同期住院的慢性乙型肝炎患者30例(CHB组)和健康体检者30例(健康对照组)。比较3组患者血清IL-37和肝功能指标的差异,分析HBV-ACLF患者血清IL-37水平与肝功能指标及患者预后的关系。结果 HBV-ACLF组血清IL-37水平显著高于CHB组和健康对照组(P<0.05)。HBV-ACLF患者晚期组血清IL-37水平显著高于中期组和早期组(P<0.05),中期组显著高于早期组(P<0.05)。HBV-ACLF患者血清IL-37水平与丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)水平呈正相关(rs分别为0.52、0.72)。随访2个月,共22例患者发生感染,39例死亡;感染患者和死亡患者血清IL-37水平分别高于非感染患者和存活患者(P<0.05)。结论HBV-ACLF患者血清IL-37水平与患者病情严重程度有关,可在一定程度上反映患者的预后。
Objective To investigate the expression of interleukin-37(IL-37) in patients with hepatitis B virusrelated acute-on-chronic liver failure(HBV-ACLF) and its clinical significances.MethodsEighty-one patients with HBV-ACLF admitted to our hospital from June 2015 to June 2017 were enrolled as study subjects(HBV-ACLB group),and30 patients with chronic hepatitis B(CHB) were used as CHB group and 30 healthy people with physical examination were used as control group. In HBV-ACLB group there were 25 patients at early stage,32 cases at middle stage and 24 cases at advanced stage at admission. Markers of liver function and serum levels of IL-37 were compared between three groups of patients. Pearson or Spearman correlation analysis were used to analyze the correlation between IL-37 level and markers ofliver function,and the prognosis of HBV-ACLF.ResultsThere was significantly higher serum level of IL-37 in HBV-ACLF group than that of CHB and control groups(P<0.05). Among the patients with HBV-ACLF,those in the advancedstage had significantly higher levels of IL-37 than those in the patients with middle stage and early stage,and those in themiddle stage had significantly higher levels of IL-37 than those in the early stage(P<0.05). There were positive correlationbetween IL-37,alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in HBV-ACLF group(rsvalues were0.52 and 0.72,respectively). Among 81 cases of HBV-ACLF,22 cases acquired infection and 39 cases died during the 2-month follow-up period. The serum levels of IL-37 were significantly higher in the infected cases and death cases than thosein the non-infected cases and survival cases(P<0.05).ConclusionThe serum level of IL-37 is associated with theseverity of HBV-ACLF,and which can be used as an important prognostic marker for ACLF.
Objective To investigate the expression of interleukin-37(IL-37) in patients with hepatitis B virusrelated acute-on-chronic liver failure(HBV-ACLF) and its clinical significances.MethodsEighty-one patients with HBV-ACLF admitted to our hospital from June 2015 to June 2017 were enrolled as study subjects(HBV-ACLB group),and30 patients with chronic hepatitis B(CHB) were used as CHB group and 30 healthy people with physical examination were used as control group. In HBV-ACLB group there were 25 patients at early stage,32 cases at middle stage and 24 cases at advanced stage at admission. Markers of liver function and serum levels of IL-37 were compared between three groups of patients. Pearson or Spearman correlation analysis were used to analyze the correlation between IL-37 level and markers ofliver function,and the prognosis of HBV-ACLF.ResultsThere was significantly higher serum level of IL-37 in HBV-ACLF group than that of CHB and control groups(P<0.05). Among the patients with HBV-ACLF,those in the advancedstage had significantly higher levels of IL-37 than those in the patients with middle stage and early stage,and those in themiddle stage had significantly higher levels of IL-37 than those in the early stage(P<0.05). There were positive correlationbetween IL-37,alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in HBV-ACLF group(rsvalues were0.52 and 0.72,respectively). Among 81 cases of HBV-ACLF,22 cases acquired infection and 39 cases died during the 2-month follow-up period. The serum levels of IL-37 were significantly higher in the infected cases and death cases than thosein the non-infected cases and survival cases(P<0.05).ConclusionThe serum level of IL-37 is associated with theseverity of HBV-ACLF,and which can be used as an important prognostic marker for ACLF.
引文
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[8]Kumar S,McDonnell PC,Lehr R,et al.Identification and initial characterization of four novel members of the interleukin-1 family[J].J Biol Chem,2000,275(14):10308-10314.
[9]Dunn E,Sims JE,Nicklin MJ,et al.Annotating genes with potential roles in the immune system:Six new members of the il-1 family[J].Trends Immunol,2001,22(10):533-536.
[10]Fujita H,Inoue Y,Seto K,et al.Interleukin-37 is elevated in subjects with atopic dermatitis[J].J Dermatol Sci,2013,69(2):173-175.doi:10.1016/j.jdermsci.2012.11.001.
[11]McNamee EN,Masterson JC,Jedlicka P,et al.Interleukin 37expression protects mice from colitis[J].Proc Natl Acad Sci USA,2011,108(140):16711-16716.doi:10.1073/pnas.1111982108.
[12]Li C,Ji H,Cai Y,et al.Serum interleukin-37 concentrations and hbeag seroconversion in chronic hbv patients during telbivudine treatment.Journal of interferon&cytokine research[J].J Interferon Cytokine Res,2013,33(10):612-618.doi:10.1089/jir.2013.0001.
[13]Brown MA.Breakthroughs in genetic studies of ankylosing spondylitis[J].Rheumatology(Oxford),2008,47(2):132-137.
[14]Ye L,Ji L,Wen Z,et al.IL-37 inhibits the production of inflammatory cytokines in peripheral blood mononuclear cells of patients with systemic lupus erythematosus:its correlation with disease activity[J].J Transl Med,2014,12:69.doi:10.1186/1479-5876-12-69.
[15]Moschen AR,Molnar C,Enrich B,et al.Adipose and liver expression of interleukin(IL)-1 family members in morbid obesity and effects of weight loss[J].Mol Med,2011,17(7/8):840-845.doi:10.2119/molmed.2010.00108.
[16]Patel FJ,Volkmann DT,Taylor GW,et al.Retracted:IL-37 reduces inflammatory response after cerebral ischemia and reperfusion injury through down-regulation of pro-inflammatory cytokines[J].Cytokine,2014,69(2):234-239.doi:10.1016/j.cyto.2014.06.011.
[17]Bulau AM,Fink M,Maucksch C,et al.In vivo expression of interleukin-37 reduces local and systemic inflammation in concanavalin A-induced hepatitis[J].The Scientific World Journal,2011,11:2480-2490.doi:10.1100/2011/968479.
[18]任东东.白介素-37抗对乙酰氨基酚诱导小鼠肝损伤的作用研究[D].泸州:四川医科大学,2015.Ren DD.The study of interleukin-37 anti-acetaminophen-induced liver injury on mice[D].Luzhou:Sichuan Medical University,2015.
[19]张超.白介素37对转化生长因子β1诱导的大鼠肝星状细胞的影响[D].泸州:泸州医学院,2014.Zhang C.Effects of interleukins 37 on transforming growth factor beta 1 induced activation of rat hepatic stellate cells[D].Luzhou:Luzhou Medical College,2014.
[20]宋颖.白介素-37对四氯化碳诱导的小鼠肝纤维化的作用研究[D].泸州:西南医科大学,2016.Song Y.Effects of interleukin-37 on hepatic fibrosis induced by carbon tetrachlorid in mice[D].Luzhou:Southwest Medical University,2016.2018-12-282019-04-22
[2]中华医学会感染病学分会肝衰竭与人工肝学组,中华医学会肝病学分会重型肝病与人工肝学组.肝衰竭诊治指南(2012年版)[J].中华肝脏病杂志,2012,5(6):321-327.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.Guidelines for diagnosis and treatment of liver failure[J].Chin J Hepatol,2012,5(6):321-327.doi:10.3760/cma.j.issn.1674-2397.2012.06.001.
[3]Liaw YF,Leung N,Kao JH,et al.Chronic Hepatitis BGWPotA-PAftSotL.Asian-pacific consensus statement on the management of chronic hepatitis B:a 2008 update[J].Hepatol Int,2008,2(3):263-283.doi:10.1007/s12072-008-9080-3.
[4]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(2010年版)[J].中华肝脏病杂志,2011,19(1):13-24.Chinese Society of Hepatology and Chinese Society ofInfectious Diseases,Chinese Medical Association,The guideline of prevention and treatment for chronic hepatitis B(2010 version)[J].Chin J Hepatol,2011,19(1):13-24.doi:10.3760/cma.j.issn.1000-6680.2011.02.001.
[5]刘晓燕,胡瑾华,王慧芬,等.1977例急性、亚急性、慢加急性肝衰竭患者的病因与转归分析[J].中华肝脏病杂志,2008,16(10):772-775.Liu XY,Hu JH,Wang HF,et al.Etiological analysis of1977 patients with acute liver failure,subacute liver failure and acute-on-chronic liver failure[J].Chin J Hepatol,2008,16(10):772-775.doi:10.3321/j.issn:1007-3418.2008.10.013.
[6]Finkenstedt A,Nachbaur K,Zoller H,et al.Acute-on-chronic liver failure:Excellent outcomes after liver transplantation but high mortality on the wait list[J].Liver Transpl,2013,19(8):879-886.doi:10.1002/lt.23678.
[7]姚勤伟,欧阳颖.慢加急性肝衰竭进展[J].北京医学,2017,39(9):987-988.Yao WQ,Ouyang Y.Progression of Acute-onchronic liver failure[J].Beijing Medical Journal,2017,39(9):987-988.doi:10.15932/j.0253-9713.2017.09.033.
[8]Kumar S,McDonnell PC,Lehr R,et al.Identification and initial characterization of four novel members of the interleukin-1 family[J].J Biol Chem,2000,275(14):10308-10314.
[9]Dunn E,Sims JE,Nicklin MJ,et al.Annotating genes with potential roles in the immune system:Six new members of the il-1 family[J].Trends Immunol,2001,22(10):533-536.
[10]Fujita H,Inoue Y,Seto K,et al.Interleukin-37 is elevated in subjects with atopic dermatitis[J].J Dermatol Sci,2013,69(2):173-175.doi:10.1016/j.jdermsci.2012.11.001.
[11]McNamee EN,Masterson JC,Jedlicka P,et al.Interleukin 37expression protects mice from colitis[J].Proc Natl Acad Sci USA,2011,108(140):16711-16716.doi:10.1073/pnas.1111982108.
[12]Li C,Ji H,Cai Y,et al.Serum interleukin-37 concentrations and hbeag seroconversion in chronic hbv patients during telbivudine treatment.Journal of interferon&cytokine research[J].J Interferon Cytokine Res,2013,33(10):612-618.doi:10.1089/jir.2013.0001.
[13]Brown MA.Breakthroughs in genetic studies of ankylosing spondylitis[J].Rheumatology(Oxford),2008,47(2):132-137.
[14]Ye L,Ji L,Wen Z,et al.IL-37 inhibits the production of inflammatory cytokines in peripheral blood mononuclear cells of patients with systemic lupus erythematosus:its correlation with disease activity[J].J Transl Med,2014,12:69.doi:10.1186/1479-5876-12-69.
[15]Moschen AR,Molnar C,Enrich B,et al.Adipose and liver expression of interleukin(IL)-1 family members in morbid obesity and effects of weight loss[J].Mol Med,2011,17(7/8):840-845.doi:10.2119/molmed.2010.00108.
[16]Patel FJ,Volkmann DT,Taylor GW,et al.Retracted:IL-37 reduces inflammatory response after cerebral ischemia and reperfusion injury through down-regulation of pro-inflammatory cytokines[J].Cytokine,2014,69(2):234-239.doi:10.1016/j.cyto.2014.06.011.
[17]Bulau AM,Fink M,Maucksch C,et al.In vivo expression of interleukin-37 reduces local and systemic inflammation in concanavalin A-induced hepatitis[J].The Scientific World Journal,2011,11:2480-2490.doi:10.1100/2011/968479.
[18]任东东.白介素-37抗对乙酰氨基酚诱导小鼠肝损伤的作用研究[D].泸州:四川医科大学,2015.Ren DD.The study of interleukin-37 anti-acetaminophen-induced liver injury on mice[D].Luzhou:Sichuan Medical University,2015.
[19]张超.白介素37对转化生长因子β1诱导的大鼠肝星状细胞的影响[D].泸州:泸州医学院,2014.Zhang C.Effects of interleukins 37 on transforming growth factor beta 1 induced activation of rat hepatic stellate cells[D].Luzhou:Luzhou Medical College,2014.
[20]宋颖.白介素-37对四氯化碳诱导的小鼠肝纤维化的作用研究[D].泸州:西南医科大学,2016.Song Y.Effects of interleukin-37 on hepatic fibrosis induced by carbon tetrachlorid in mice[D].Luzhou:Southwest Medical University,2016.2018-12-282019-04-22