Objective To investigate the association between serum interleukin( IL) and liver pathological changes in patients with chronic hepatitis B( CHB). Methods A total of 59 patients with CHB who were treated in Putuo District Central Hospital of Shanghai from February 2018 to February 2019 were enrolled as subjects,and liver biopsy was performed for all patients. According to the degree of liver inflammation,the patients were divided into mild inflammation( G1-G2) group and severe inflammation( G3-G4) group,and according to the degree of liver fibrosis,the patients were divided into mild fibrosis( S0-S2) group and severe fibrosis( S3-S4) group. Serum liver function parameters,blood lipids,interleukin-2( IL-2),interleukin-6( IL-6),interleukin-8( IL-8),and interleukin-10( IL-10)were measured for all patients. The independent samples t-test was used for comparison of normally distributed continuous data between two groups,and the Wilcoxon non-parametric test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test was used for comparison of categorical data between groups. A Spearman correlation analysis was also performed.Results The degree of liver fibrosis increased with the increase in liver inflammation( rs= 0. 538,P < 0. 001). Compared with the mild inflammation group,the severe inflammation group had significantly higher serum levels of alanine aminotransferase [95. 00( 45. 00-169. 25) U/L vs 51. 00( 29. 00-88. 00) U/L,Z =-2. 625,P = 0. 009],aspartate aminotransferase [54. 50( 34. 75-84. 50) U/L vs38. 00( 30. 00-49. 00) U/L,Z =-2. 014,P = 0. 044],and gamma-glutamyl transpeptidase [91. 00( 56. 72-192. 25) U/L vs 44. 00( 24. 00-100. 00) U/L,Z =-2. 400,P = 0. 016]. The severe fibrosis group had a significantly higher serum level of high-density lipoprotein than the mild fibrosis group [0. 97( 0. 32-1. 08) mmol/L vs 1. 23( 0. 36-1. 38) mmol/L,Z =-1. 300,P = 0. 008]. The severe inflammation group had a significantly higher serum level of IL-2 receptor than the mild inflammation group [704. 00( 418. 00-1038. 00) U/ml vs 436. 00( 335. 00-555. 00) U/ml,Z =-3. 405,P = 0. 001],and the severe fibrosis group had a significantly higher serum level of IL-2 receptor than the mild fibrosis group [735. 00( 523. 00-890. 50) U/ml vs 447. 00( 351. 50-624. 50) U/ml,Z =-5. 358,P = 0. 001]. Conclusion The degree of liver inflammation is positively correlated with that of liver fibrosis,while the serum level of IL-2 receptor increases with the increase in the degrees of liver inflammation and fibrosis,indicating that IL-2 receptor can reflect the degrees of liver inflammation and fibrosis to some extent.
[1] TERRAULT NA,BZOWEJ NH,CHANG KM,et al. AASLD guidelines for treatment of chronic hepatitis B[J]. Hepatology,2016,63(1):261-283.
|
[2] Polaris Observatory Collaborators. Global prevalence,treatment,and prevention of hepatitis B virus infection in 2016:A modelling study[J]. Lancet Gastroenterol Hepatol,2018,3(6):383-403.
|
[3] CALVENTE CJ,TAMEDA M,JOHNSON CD,et al. Neutrophils contribute to spontaneous resolution of liver inflammation and fibrosis via microRNA-223[J]. J Clin Invest,2019,129(10):4091-4109.
|
[4] CHANG ML,YANG SS. Metabolic signature of hepatic fibrosis:From individual pathways to systems biology[J]. Cells,2019,8(11):1423.
|
[5] DENG YQ,ZHAO H,MA AL,et al. Selected cytokines serve as potential biomarkers for predicting liver inflammation and fibrosis in chronic hepatitis B patients with normal to mildly elevated aminotransferases[J]. Medicine(Baltimore),2015,94(45):e2003.
|
[6] KARLMARK KR,WEISKIRCHEN R,ZIMMERMANN HW,et al.Hepatic recruitment of the inflammatory Gr1+monocyte subset upon liver injury promotes hepatic fibrosis[J]. Hepatology,2009,50(1):261-274.
|
[7] MURAKAMI S. Soluble interleukin-2 receptor in cancer[J].Front Biosci,2004,9:3085-3090.
|
[8] SUN Y,GU J,LIU R,et al. IL-2/IL-6 ratio correlates with liver function and recovery in acute liver injury patients[J].APMIS,2019,127(6):468-474.
|
[9] 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.
|
[10] ORITO E,FUJIWARA K,KANIE H,et al. Quantitation of HBsAg predicts response to entecavir therapy in HBV genotype C patients[J]. World J Gastroenterol,2012,18(39):5570-5575.
|
[11] CHEN YC,JENG WJ,CHU CM,et al. Decreasing levels of HBsAg predict HBs Ag seroclearance in patients with inactive chronic hepatitis B virus infection[J]. Clin Gastroenterol Hepatol,2012,10(3):297-302.
|
[12] HSU A,LAI CL,YUEN MF. Update on the risk of hepatocellular carcinoma in chronic hepatitis B virus infection[J]. Curr Hepat Rep,2011,10(2):106-111.
|
[13] XIONG M,LI J,YANG S,et al. Influence of gender and reproductive factors on liver fibrosis in patients with chronic hepatitis B infection[J]. Clin Transl Gastroenterol,2019,10(10):e00085.
|
[14] CHIEN TL,WANG JH,KEE KM,et al. Factors predicting HBsAg seroclearance and alanine transaminase elevation in HBe Ag-negative hepatitis B virus-infected patients with persistently normal liver function[J]. PLo S One,2016,11(12):e0166543.
|
[15] SETO WK,LAI CL,IP PP,et al. A large population histology study showing the lack of association between ALT elevation and significant fibrosis in chronic hepatitis B[J]. PLo S One,2012,7(2):e32622.
|
[16] CHEN XL,HAN YD,WANG H. Relations of hepatic steatosis with liver functions,inflammations,glucolipid metabolism in chronic hepatitis B patients[J]. Eur Rev Med Pharmacol Sci,2018,22(17):5640-5646.
|
[17] DUM,ZHANG S,XIAO L,et al. The relationship between serum bilirubin and elevated fibrotic indices among HBV carriers:A cross-sectional study of a Chinese population[J]. Int J Mol Sci,2016,17(12):e2057.
|
[18] MILLONIG G,REIMANN FM,FRIEDRICH S,et al. Extrahepatic cholestasis increases liver stiffness(FibroScan)irrespective of fibrosis[J]. Hepatology,2008,48(5):1718-1723.
|
[19] RAMACHANDRAN J,SAJITH KG,PRIYA S,et al. Serum cholinesterase is an excellent biomarker of liver cirrhosis[J]. Trop Gastroenterol,2014,35(1):15-20.
|
[20] JIANG Q,MAO R,WU J,et al. Platelet activation during chronic hepatitis B infection exacerbates liver inflammation and promotes fibrosis[J]. J Med Virol,2019.[Online ahead of print]
|
[21] SEIDLER S,ZIMMERMANN HW,WEISKIRCHEN R,et al. Elevated circulating soluble interleukin-2 receptor in patients with chronic liver diseases is associated with non-classical monocytes[J]. BMC Gastroenterol,2012,12:38.
|
[22] LAN T,CHANG L,WU L,et al. IL-6 plays a crucial role in HBV infection[J]. J Clin Transl Hepatol,2015,3(4):271-276.
|
[23] WANG X,YAN Z,YE Q. Interleukin-6 gene polymorphisms and susceptibility to liver diseases:A meta-analysis[J].Medicine(Baltimore),2019,98(50):e18408.
|
[24] YANG K,GUAN SH,ZHANG H,et al. Enhanced levels of interleukin-8 are associated with hepatitis B virus infection and resistance to interferon-alpha therapy[J]. Int J Mol Sci,2014,15(11):21286-21298.
|
[25] SUH YG,KIM JK,BYUN JS,et al. CD11b(+)Gr1(+)bone marrow cells ameliorate liver fibrosis by producing interleukin-10 in mice[J]. Hepatology,2012,56(5):1902-1912.
|
[26] LIU Y,CHENG LS,WU SD,et al. IL-10-producing regulatory B-cells suppressed effector T-cells but enhanced regulatory T-cells in chronic HBV infection[J]. Clin Sci(Lond),2016,130(11):907-919.
|