中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 36 Issue 6
Jun.  2020
Turn off MathJax
Article Contents

Expression features of glucocorticoid receptor and its association with treatment outcome in patients with hepatitis B virus-related acute-on-chronic liver failure

DOI: 10.3969/j.issn.1001-5256.2020.06.013
Research funding:

 

  • Received Date: 2020-01-20
  • Published Date: 2020-06-20
  • Objective To investigate the expression features of glucocorticoid receptor( GR) and its subtypes α and β in patients with early-or middle-stage hepatitis B virus-related acute/subacute-on-chronic liver failure( HBV-ACLF) treated by glucocorticoid( GC) and their association with sensitivity to glucocorticoid therapy. Methods A prospective non-randomized controlled trial was performed for 33 patients with early-or middle-stage HBV-ACLF who were hospitalized and treated in Beijing YouAn Hospital from September 2015 to June2018,and among these patients,18 received intravenous infusion of methylprednisolone for 7 days in addition to comprehensive medical treatment. Flow cytometry and RT-PCR were used to measure the mRNA expression of GR,GR-α,and GR-β,and the expression of GR,GR-α,and GR-β was observed at baseline and on day 8. According to the response to GC on day 10,the hormone group was further divided into hormone-sensitive group with 13 patients and hormone-insensitive group with 5 patients. The two-independent-samples t test was used for comparison of continuous data between two groups,and the paired t-test was used for comparison within one group before and after treatment; the Fisher's exact test was used for comparison of categorical data between groups. The Kaplan-Meier survival curve was used to analyze 28-day survival,and the log-rank test was used for comparison between groups. Results The hormone group had a significant reduction in the mRNA expression of GR-α on day 8 after hormone administration [( 0. 99 ± 0. 48) × 10-2 vs( 1. 96 ±0. 50) × 10-2,t = 6. 586,P < 0. 001]There was a significant difference in the mRNA expression of GR-α between the hormone group and the non-hormone group on day 8 [0. 99 ± 0. 48) × 10-2 vs( 1. 70 ± 0. 66) × 10-2,t =-3. 518,P = 0. 001]On day 8,the hormone-sensitive group had significantly higher mRNA expression of GR-α than the hormone-insensitive group [1. 21 ± 0. 34) × 10-2 vs( 0. 43 ± 0.31) × 10-2,t = 4. 456,P < 0. 001]and the hormone-sensitive group had a significantly greater reduction in the mRNA expression of GR-α compared with the hormone-insensitive group( t =-2. 904,P = 0. 01). There was no significant difference in the mRNA expression of GR-β on day 8 between the hormone-sensitive group and the hormone-insensitive group [0. 14 ± 0. 08) × 10-2 vs( 0. 10 ±0. 04) × 10-2,t = 1. 092,P = 0. 291]For the hormone group,the mean ratio of reduction in GR-α mRNA expression to baseline value was46% on day 8,and according to this,the patients were divided into ≤46% group with 10 patients and > 46% group with 8 patients. There was a significant difference in the ratio of reduction in GR-α mRNA expression to baseline value between the two groups( 26. 99% ± 25.09% vs 70. 09% ± 16. 08%,t =-4. 203,P = 0. 001). On day 10,there were significant differences between the ≤46% group and the >46% group in the ratio of reduction in total bilirubin( TBil) to baseline value( P = 0. 021) and the ratio of increase in prothrombin time activity( PTA) to baseline value( P = 0. 048). Conclusion In patients with early-or middle-stage HBV-ACLF,there is a significant reduction in the mRNA expression of GR-α after GC treatment. Patients sensitive to hormone have a relatively low degree of reduction in the mRNA expression of GR-α,with better improvements in TBil and PTA on day 28 than those insensitive to hormone. Dynamic change of GR-α mRNA has a certain reference value in predicting the outcome of hormone therapy.

     

  • loading
  • [1] Liver Failure and Artificial Liver Group,Chinese Society of Infectious Diseases,Chinese Medical Association,Severe Liver Disease and Amficial Liver Group,Chinese Society of Hepatology, Chinese Medical Association. Guideline for diagnosis and treatment of liver failure(2012)[J]. J Clin Hepatol,2013,16(3):210-216.(in Chinese)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].实用肝脏病杂志,2013,16(3):210-216.
    [2] ZHANG HY,ZHANG XQ. Predictive model for the efficacy of glucocorticoids in treating acute-on-chronic preliver failure and road map[J]. Chin J Gastroenterol Hepatol,2016,25(5):21-24.(in Chinese)张辉艳,张绪清.糖皮质激素治疗慢加急性肝衰竭前期的疗效预测模型与路线图[J].胃肠病学和肝病学杂志,2016,25(5):21-24.
    [3] KOGA Y,MATSUZAKI A,SUMINOE A,et al. Differential mRNA expression of glucocorticoid receptor alpha and beta is associated with glucocorticoid sensitivity of acute lymphoblastic leukemia in children[J]. Pediatr Blood Cancer,2005,45(2):121-127.
    [4] CHEN JF,WANG KW,ZHANG SQ,et al. Dexamethasone in outcome of patients with hepatitis B virus-related acute-onchronic liver failure[J]. J Gastroenterol Hepatol,2014,29(4):800-806.
    [5] DUAN ZP,CHEN Y. Recent progress and future perspectives of liver failure diagnosis and treatment strategies[J]. J Clin Hepatol,2012,28(10):721-725.(in Chinese)段钟平,陈煜.肝衰竭诊疗:进展与展望[J].临床肝胆病杂志,2012,28(10):721-725.
    [6] ZHANG HY,ZHANG XQ. Mechanisms of glucocorticoids in preventing the development and progress of liver failure[J]. Chin J Gastroenterol Hepatol,2016,25(5):481-484.(in Chinese)张辉艳,张绪清.糖皮质激素阻止肝衰竭发生与发展的机制[J].胃肠病学和肝病学杂志,2016,25(5):481-484.
    [7] OAKLEY RH,CIDLOWSKI JA. The biology of the glucocorticoid receptor:New signaling mechanisms in health and disease[J]. J Allergy Clin Immunol,2013,132(5):1033-1044.
    [8] WEI SD,LI JZ,LIU ZJ,et al. Dexamethasone attenuates lipopolysaccharide-induced liver injury by downregulating glucocorticoid-induced tumor necrosis factor receptor ligand in Kupffer cells[J]. Hepatol Res,2011,41(10):989-999.
    [9] BASCHANT U,TUCKERMANN J. The role of the glucocorticoid receptor in inflammation and immunity[J]. J Steroid Biochem Mol Biol,2010,120(2-3):69-75.
    [10] LIANG Y,SONG MM,LIU SY,et al. Relationship between expression of glucocorticoid receptor isoforms and glucocorticoid resistance in immune thrombocytopenia[J]. Hematology,2016,21(7):440-446.
    [11] HGG PM,HURSKAINEN T,PALATSI R,et al. Increased expression of glucocorticoid receptor beta in lymphocytes of patients with severe atopic dermatitis unresponsive to topical corticosteroid[J]. Br J Dermatol,2010,162(2):318-324.
    [12] JAKIEA B,BOCHENEK G,SANAK M. Glucocorticoid receptor isoforms in steroid-dependent asthma[J]. Pol Arch Med Wewn,2010,120(6):214-222.
    [13] GAO L,WANG JF,XIANG M,et al. Expression of human glucocorticoid receptor in T lymphocytes in acute-on-chronic hepatitis B liver failure[J]. Dig Dis Sci,2011,56(9):2605-2612.
    [14] URZUA CA,GUERRERO J,GATICA H,et al. Evaluation of the glucocorticoid receptor as a biomarker of treatment response in Vogt-Koyanagi-Harada disease[J]. Invest Ophthalmol Vis Sci,2017,58(2):974-980.
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Article Metrics

    Article views (715) PDF downloads(170) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return