Objective To investigate the correlation between serum interleukin- 1 receptor antagonist( IL- 1Ra) level and disease severity in patients with acute- on- chronic hepatitis B liver failure( HBV- ACLF). Methods A total of 31 patients with HBV- ACLF who visited Fuzhou Infectious Disease Hospital from October 2013 to January 2015 were enrolled as study subjects. Another 28 patients with acute hepatitis B( AHB) and 30 patients with chronic hepatitis B( CHB) were enrolled as controls. The Q- Plex was used to measure the peripheral blood concentrations of cytokines including IL- 1Ra,interleukin- 1β( IL- 1β),interleukin- 6( IL- 6),interleukin- 4,interleukin- 10,tumor necrosis factorα( TNFα),and interferonγ. Liver function and coagulation function were examined for each group,and the correlations of concentrations of serum cytokines including IL- 1Ra with Model for End- Stage Liver Disease( MELD) score and HBV DNA were analyzed. The Kruskal- Wallis H test was used for comparison of continuous data between multiple groups,and the Mann- Whitney U test was used for comparison between any two groups; the chi- square test was used for comparison of categorical data between groups. The Spearman rank correlation was used for correlation analysis. Results The IL- 1Ra level and IL- 1Ra / IL- 1β ratio showed significant differences between the three groups( all P < 0. 05),and the HBV- ACLF group had a significantly higher IL- 1Ra level than the CHB group and the AHB group [186. 46( 162. 68-512. 90) pg/ml vs 70. 47( 47. 07-92. 47) pg/ml,Z =6. 300,P <0. 001; 186. 46( 162. 68-512. 90) pg/ml vs 143. 69( 117. 75-208. 54) pg / ml,Z = 2. 505,P = 0. 012]. The HBV- ACLF group had a significantly lower IL- 1Ra / IL- 1β ratio than the AHB group[2. 92( 2. 20- 4. 74) vs 4. 54( 2. 75- 6. 05),Z = 1. 966,P = 0. 048],but a significantly higher IL- 1Ra/IL- 1β ratio than the CHB group [2. 92( 2. 20- 4. 74) vs 2. 49( 1. 50- 2. 50),Z = 2. 682,P < 0. 001]. The HBV- ACLF group had significantly higher IL- 1β,IL- 6,and TNFα levels than the other two groups( all P < 0. 01). Serum IL- 1Ra level was negatively correlated with total bilirubin( TBil) and MELD score( r =- 0. 506 and- 0. 818,both P < 0. 01) but was positively correlated with prothrombin activity( PTA)( r =0. 475,P = 0. 007). Conclusion IL- 1Ra is negatively correlated with TBil and MELD score and positively correlated with PTA,which are the indicators for the severity of HBV- ACLF. IL- 1Ra may play an important role in the pathogenesis of HBV- ACLF.
[1]JALAN R,YURDAYDIN C,BAJAJ JS,et al.Toward an improved definition of acute-on-chronic liver failure[J].Gastroenterology,2014,147(1):4-10.
|
[2]LIU H,CHEN G,GAN XM.Research advances in new approaches to treatment of acute-on-chronic liver failure[J].J Clin Hepatol,2015,31(9):1496-1500.(in Chinese).刘洪,陈刚,甘雪梅.慢加急性肝衰竭治疗的新技术及其研究进展[J].临床肝胆病杂志,2015,31(9):1496-1500.
|
[3]LIU Q.Role of cytokines in the pathophysiology of acute-on-chronic liver failure[J].Blood Purification,2009,28(4):331-341.
|
[4]SARIN SK,KEDARISETTY CK,ABBAS Z,et al.Acute-on-chronic liver failure:consensus recommendations of the Asian Pacific Association for the Study of the Liver(APASL)2014[J].Hepatol Int,2014,8(4):453-471.
|
[5]National Clinical Guideline Centre(UK).Hepatitis B(chronic):diagnosis and management of chronic hepatitis b in children,young people and adults[EB/OL].NICE Clinical Guidelines(No 165)[2013-06].http://www.ncbi.nlm.nih.gov/pubmed/25473721
|
[6]WANG DW,YIN YM,YAO YM.Advances in the management of acute liver failure[J].World J Gastroenterol,2013,19(41):7069-7077.
|
[7]BODE JG,ALBRECHT U,HAUSSINGER D,et al.Hepatic acute phase proteins—regulation by IL-6-and IL-1-type cytokines involving STAT3 and its crosstalk with NF-kappaB-dependent signaling[J].Eur J Cell Biol,2012,91(6-7):496-505.
|
[8]SHI XL,ZHU W,TAN JJ,et al.Effect evaluation of interleukin-1 receptor antagonist nanoparticles for mesenchymal stem cell transplantation[J].World J Gastroenterol,2013,19(12):1984-1991.
|
[9]MOLL M,KUEMMERLE-DESCHNER JB.Inflammasome and cytokine blocking strategies in autoinflammatory disorders[J].Clin Immunol,2013,147(3):242-275.
|
[10]HOPE S,UELAND T,STEEN NE,et al.Interleukin 1 receptor antagonist and soluble tumor necrosis factor receptor 1 are associated with general severity and psychotic symptoms in schizophrenia and bipolar disorder[J].Schizophrenia research,2013,145(1-3):36-42.
|
[11]ZHENG YB,ZHANG XH,HUANG ZL,et al.Amniotic-fluid-derived mesenchymal stem cells overexpressing interleukin-1 receptor antagonist improve fulminant hepatic failure[J].PLoS One,2012,7(7):e41392.
|
[12]SGROI A,GONELLE-GISPERT C,MOREL P,et al.Interleukin-1 receptor antagonist modulates the early phase of liver regeneration after partial hepatectomy in mice[J].PLoS One,2011,6(9):e25442.
|
[13]DINARELLO CA.Immunological and inflammatory functions of the interleukin-1 family[J].Annu Rev Immunol,2009,27:519-550.
|
[14]HU J,YAN D,GAO J,et al.rh IL-1Ra reduces hepatocellular apoptosis in mice with acetaminophen-induced acute liver failure[J].Lab Invest,2010,90(12):1737-1746.
|