中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 38 Issue 1
Jan.  2022
Turn off MathJax
Article Contents
Article Navigation >  Journal of Clinical Hepatology  > 2022  >  38(1): 91-96

Clinical effect of direct-acting antiviral agents in treatment of chronic hepatitis C patients with thrombocytopenia

DOI: 10.3969/j.issn.1001-5256.2022.01.014

  • Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases; Artificial Cell Engineering Technology Research Center, Tianjin 300170, China

Research funding:

Tianjin Science and Technology Major Project and Critical Disease Prevention and Control Project 2019 (19ZXDBSY00030)

  • Received Date: 2021-04-24
  • Accepted Date: 2021-06-29
  • Published Date: 2022-01-20
    Abstract
  •   Objective  To investigate the clinical effect of direct-acting antiviral agent (DAA) in the treatment of chronic hepatitis C (CHC) patients with thrombocytopenia and its effect on platelet count (PLT).  Methods  A retrospective analysis was performed for 83 CHC patients with thrombocytopenia (PLT < 150×109/L) who received the DAA treatment regimen without interferon for 12-24 weeks in Tianjin Third Central Hospital from April 2018 to March 2019, and the changes in virologic response, liver function parameters, PLT, and liver stiffness measurement (LSM) were evaluated at the end of treatment (EOT) and at week 12 after EOT. Quantitative data accord with normal distribution were compared by repeated measures ANOVA. Normal transformation was performed before the comparison between skewed data, then repeated measures ANOVA was carried out. A logistic regression analysis was used to investigate the predictive factors for PLT elevation, and the receiver operating characteristic (ROC) curve was plotted to analyze the value of LSM in predicting PLT elevation after treatment.  Results  Among the 83 CHC patients with thrombocytopenia, 61.4% had liver cirrhosis, and the rate of sustained virologic response at week 12 after the end of treatment (SVR12) was 98.8%. From baseline to EOT and SVR12, the patients had significant reductions in the serum levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, total bilirubin, and globin, a significant increase in the serum level of albumin, and a significant reduction in LSM (all P < 0.05). For all patients, PLT at EOT and SVR12 was significantly higher than that at baseline [EOT vs baseline: (110.4±44.6)×109/L vs (97.8±33.2)×109/L, P < 0.01; SVR12 vs baseline: (109.0±47.7)×109/L vs (97.8±33.2)×109/L, P < 0.01]. At SVR12, there were significant differences in the proportion of patients with liver cirrhosis, baseline LSM, and baseline white blood cell count between the PLT elevation group and the non-PLT elevation group (all P < 0.05). The multivariate logistic regression analysis showed that LSM was an independent predictive factor for significant PLT elevation after DAA treatment (odds ratio=0.929, 95% confidence interval: 0.864-0.999, P < 0.05). Baseline LSM had an area under the ROC curve of 0.644 in predicting PLT elevation, with a sensitivity of 81.0% and a specificity of 48.6% at a cut-off value of 20.15 kPa. The patients with PLT > 100×109/L at baseline had a greater increase in PLT(P < 0.05).  Conclusion  CHC patients with thrombocytopenia have significant improvements in liver function and LSM after receiving DAA treatment and obtaining SVR12, and baseline LSM is an independent predictive factor for PLT elevation. There is a significant increase in PLT from baseline to EOT and SVR12.

     

    • FullText(HTML)
  • loading
    • References(33)
  • [1]
    WEDEMEYER H, DORE GJ, WARD JW. Estimates on HCV disease burden worldwide - filling the gaps[J]. J Viral Hepat, 2015, 22(Suppl 1): 1-5. DOI: 10.1111/jvh.12371.
    [2]
    GONZALEZ HC, DUARTE-ROJO A. Virologic cure of hepatitis C: Impact on hepatic fibrosis and patient outcomes[J]. Curr Gastroenterol Rep, 2016, 18(7): 32. DOI: 10.1007/s11894-016-0508-y.
    [3]
    LOUIE KS, MICALLEF JM, PIMENTA JM, et al. Prevalence of thrombocytopenia among patients with chronic hepatitis C: A systematic review[J]. J Viral Hepat, 2011, 18(1): 1-7. DOI: 10.1111/j.1365-2893.2010.01366.x.
    [4]
    KEE KM, WANG JH, HUNG CH, et al. Improvement of thrombocytopenia in hepatitis C-related advanced fibrosis patients after sustained virological response[J]. Dig Dis Sci, 2013, 58(2): 556-561. DOI: 10.1007/s10620-012-2380-4.
    [5]
    van der MEER AJ, MAAN R, VELDT BJ, et al. Improvement of platelets after SVR among patients with chronic HCV infection and advanced hepatic fibrosis[J]. J Gastroenterol Hepatol, 2016, 31(6): 1168-1176. DOI: 10.1111/jgh.13252.
    [6]
    Chinese Society of Hepatology, Chinese Society of Infectious Diseases, Chinese Medical Association. The guideline of prevention and treatment for hepatitis C: A 2015 update[J]. J Clin Hepatol, 2015, 31(12): 1961-1979. DOI: 10.3969/j.issn.1001-5256.2015.12.003.

    中华医学会肝病学分会, 中华医学会感染病学会分会. 丙型肝炎防治指南(2015年更新版)[J]. 临床肝胆病杂志, 2015, 31(12): 1961-1979. DOI: 10.3969/j.issn.1001-5256.2015.12.003.
    [7]
    European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2018[J]. J Hepatol, 2018, 69(2): 461-511. DOI: 10.1016/j.jhep.2018.03.026.
    [8]
    Chinese Society of Hepatology, Chinese Medical Association. Chinese guidelines on the management of liver cirrhosis[J]. J Clin Hepatol, 2019, 35(11): 2408-2425. DOI: 10.3969/j.issn.1001-5256.2019.11.006.

    中华医学会肝病学分会. 肝硬化诊治指南[J]. 临床肝胆病杂志, 2019, 35(11): 2408-2425. DOI: 10.3969/j.issn.1001-5256.2019.11.006.
    [9]
    HUI P, COOK DJ, LIM W, et al. The frequency and clinical significance of thrombocytopenia complicating critical illness: A systematic review[J]. Chest, 2011, 139(2): 271-278. DOI: 10.1378/chest.10-2243.
    [10]
    CHEN YC, TSENG CW, TSENG KC. Rapid platelet count improvement in chronic hepatitis C patients with thrombocytopenia receiving direct-acting antiviral agents[J]. Medicine (Baltimore), 2020, 99(19): e20156. DOI: 10.1097/MD.0000000000020156.
    [11]
    DIETRICH CF, BAMBER J, BERZIGOTTI A, et al. EFSUMB guidelines and recommendations on the clinical use of liver ultrasound elastography, update 2017 (long version)[J]. Ultraschall Med, 2017, 38(4): e48. DOI: 10.1055/a-0641-0076.
    [12]
    Chinese Society of Hepatology, Chinese Medical Association, Chinese Society of Infectious Diseases, Chinese Medical Association. Guidelines for the prevention and treatment of hepatitis C(2019 version)[J]. J Clin Hepatol, 2019, 35(12): 2670-2686. DOI: 10.3969/j.issn.1001-5256.2019.12.008.

    中华医学会肝病学分会, 中华医学会感染病学分会. 丙型肝炎防治指南(2019年版)[J]. 临床肝胆病杂志, 2019, 35(12): 2670-2686. DOI: 10.3969/j.issn.1001-5256.2019.12.008.
    [13]
    EL-SERAG HB, CHRISTIE IC, PUENPATOM A, et al. The effects of sustained virological response to direct-acting anti-viral therapy on the risk of extrahepatic manifestations of hepatitis C infection[J]. Aliment Pharmacol Ther, 2019, 49(11): 1442-1447. DOI: 10.1111/apt.15240.
    [14]
    HERMOS JA, QUACH L, GAGNON DR, et al. Incident severe thrombocytopenia in veterans treated with pegylated interferon plus ribavirin for chronic hepatitis C infection[J]. Pharmacoepidemiol Drug Saf, 2014, 23(5): 480-488. DOI: 10.1002/pds.3585.
    [15]
    HUANG CF, YEH ML, HUANG CI, et al. Interference of hepatitis B virus dual infection in platelet count recovery in chronic hepatitis C patients with curative antiviral therapy[J]. J Gastroenterol Hepatol, 2018, 33(5): 1108-1114. DOI: 10.1111/jgh.14017.
    [16]
    LOUIE KS, MICALLEF JM, PIMENTA JM, et al. Prevalence of thrombocytopenia among patients with chronic hepatitis C: A systematic review[J]. J Viral Hepat, 2011, 18(1): 1-7. DOI: 10.1111/j.1365-2893.2010.01366.x.
    [17]
    RAWI S, WU GY. Pathogenesis of thrombocytopenia in chronic HCV infection: A review[J]. J Clin Transl Hepatol, 2020, 8(2): 184-191. DOI: 10.14218/JCTH.2020.00007.
    [18]
    OSADA M, KANEKO M, SAKAMOTO M, et al. Causes of thrombocytopenia in chronic hepatitis C viral infection[J]. Clin Appl Thromb Hemost, 2012, 18(3): 272-280. DOI: 10.1177/1076029611429124.
    [19]
    AREF S, SLEEM T, EL MENSHAWY N, et al. Antiplatelet antibodies contribute to thrombocytopenia associated with chronic hepatitis C virus infection[J]. Hematology, 2009, 14(5): 277-281. DOI: 10.1179/102453309X439818.
    [20]
    OGAWA E, FURUSYO N, NAKAMUTA M, et al. Glecaprevir and pibrentasvir for Japanese patients with chronic hepatitis C genotype 1 or 2 infection: Results from a multicenter, real-world cohort study[J]. Hepatol Res, 2019, 49(6): 617-626. DOI: 10.1111/hepr.13328.
    [21]
    SEKO Y, MORIGUCHI M, TAKAHASHI A, et al. The association between the platelet count and liver volume in compensated cirrhosis patients after the eradication of hepatitis C virus by direct-acting antivirals[J]. Intern Med, 2020, 59(15): 1811-1817. DOI: 10.2169/internalmedicine.4442-20.
    [22]
    DAI CY, HO CK, HUANG JF, et al. Hepatitis C virus viremia and low platelet count: A study in a hepatitis B & C endemic area in Taiwan[J]. J Hepatol, 2010, 52(2): 160-166. DOI: 10.1016/j.jhep.2009.11.017.
    [23]
    KAJIHARA M, KATO S, OKAZAKI Y, et al. A role of autoantibody-mediated platelet destruction in thrombocytopenia in patients with cirrhosis[J]. Hepatology, 2003, 37(6): 1267-1276. DOI: 10.1053/jhep.2003.50209.
    [24]
    HONMA Y, SHIBATA M, HAYASHI T, et al. Effect of direct-acting antivirals on platelet-associated immunoglobulin G and thrombocytopenia in hepatitis C virus-related chronic liver disease[J]. Liver Int, 2019, 39(9): 1641-1651. DOI: 10.1053/jhep.2003.50209.
    [25]
    SHAO LN, ZHANG ST, WANG N, et al. Platelet indices significantly correlate with liver fibrosis in HCV-infected patients[J]. PLoS One, 2020, 15(1): e0227544. DOI: 10.1371/journal.pone.0227544.
    [26]
    GOTLIEB N, SCHWARTZ N, ZELBER-SAGI S, et al. Longitudinal decrease in platelet counts as a surrogate marker of liver fibrosis[J]. World J Gastroenterol, 2020, 26(38): 5849-5862. DOI: 10.3748/wjg.v26.i38.5849.
    [27]
    KODA M, MATUNAGA Y, KAWAKAMI M, et al. FibroIndex, a practical index for predicting significant fibrosis in patients with chronic hepatitis C[J]. Hepatology, 2007, 45(2): 297-306. DOI: 10.1002/hep.21520.
    [28]
    COVERDALE SA, SAMARASINGHE DA, LIN R, et al. Changes in antipyrine clearance and platelet count, but not conventional liver tests, correlate with fibrotic change in chronic hepatitis C: Value for predicting fibrotic progression[J]. Am J Gastroenterol, 2003, 98(6): 1384-1390. DOI: 10.1111/j.1572-0241.2003.07468.x.
    [29]
    TANIGUCHI H, IWASAKI Y, FUJIWARA A, et al. Long-term monitoring of platelet count, as a non-invasive marker of hepatic fibrosis progression and/or regression in patients with chronic hepatitis C after interferon therapy[J]. J Gastroenterol Hepatol, 2006, 21(1 Pt 2): 281-287. DOI: 10.1111/j.1440-1746.2006.04201.x.
    [30]
    CHANG Y, KIM JI, LEE B, et al. Clinical application of ultrasonography-guided percutaneous liver biopsy and its safety over 18 years[J]. Clin Mol Hepatol, 2020, 26(3): 318-327. DOI: 10.3350/cmh.2019.0019n.
    [31]
    NAKAGOMI R, TATEISHI R, MASUZAKI R, et al. Liver stiffness measurements in chronic hepatitis C: Treatment evaluation and risk assessment[J]. J Gastroenterol Hepatol, 2019, 34(5): 921-928. DOI: 10.1111/jgh.14530.
    [32]
    WANG JH, CHANGCHIEN CS, HUNG CH, et al. Liver stiffness decrease after effective antiviral therapy in patients with chronic hepatitis C: Longitudinal study using FibroScan[J]. J Gastroenterol Hepatol, 2010, 25(5): 964-969. DOI: 10.1111/j.1440-1746.2009.06194.x.
    [33]
    ABDEL ALEM S, ELSHARKAWY A, EL AKEL W, et al. Liver stiffness measurements and FIB-4 are predictors of response to sofosbuvir-based treatment regimens in 7256 chronic HCV patients[J]. Expert Rev Gastroenterol Hepatol, 2019, 13(10): 1009-1016. DOI: 10.1080/17474124.2019.1653183.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 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

    Figures(2)  / Tables(4)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (694) PDF downloads(64) Cited by()
    Proportional views
    Related
        

    The first journal specializing in hepatobiliary and pancreatic diseases in China

    Supervisor：Ministry of Education of the People's Republic of China

    Sponsor：Jilin University

    Academic Support: Chinese Society of Hepatology，Chinese Medical Association

    Address: 461 Xinjiang Road, Changchun

    Submit：0431-88782044

    Peer review：0431-88783542

    Email：lcgdb@vip.163.com

    About Journal

    Submission Guideline

    Journal Online

    Hepatobiliary College

    Guidelines

    YesterdayIP[]YesterdayPV[]TodayIP[]TodayPV[]Online[]

    Website Design © 2020 Editorial Board of Journal of Clinical Hepatology 吉ICP备10000617号-1 Supported by: Beijing Renhe Information Technology Co. Ltd  

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return