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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 37 Issue 7
Jul.  2021
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Article Navigation >  Journal of Clinical Hepatology  > 2021  >  37(7): 1529-1533

Value of a nomogram model in predicting significant liver injury in patients with immune-tolerant phase chronic hepatitis B

DOI: 10.3969/j.issn.1001-5256.2021.07.010
  • 1.

    Department of Liver Diseases, Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China

  • 2.

    The Second Clinical Medical School of Southern Medical University, Guangzhou 510515, China

  • 3.

    Peking University 302 Clinical Medical School, Beijing 100039, China

Research funding:

Medical Big Data and Artificial Intelligence Development Fund of Chinese PLA General Hospital (2019MBD-024);

the Capital Characteristic Clinic Project of Beijing Municipal Science and Technology Commission (Z181100001718034);

Key Project of Jumei Special Fund for Hepatobiliary Disease Prevention and Treatment (2018JM12603003)

  • Received Date: 2021-04-07
  • Accepted Date: 2021-04-21
  • Published Date: 2021-07-20
    Abstract
  •   Objective  To investigate the high-risk factors for significant liver injury in patients with immune-tolerant phase chronic hepatitis B (IT-CHB), and to establish a nomogram predictive model.  Methods  A retrospective analysis was performed for the data of 382 patients with chronic HBV infection who underwent liver biopsy in The Fifth Medical Center of Chinese PLA General Hospital from August 2002 to December 2017, and according to the presence or absence of significant liver injury, the patients were divided into significant liver injury group (≥G2/S2) with 82 patients and non-significant liver injury group with 300 patients. The independent samples t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the Kruskal-Wallis H test was used for comparison between multiple groups; the chi-square test was used for comparison of categorical data between groups. The Spearman rank correlation test was used to investigate correlation. Univariate and multivariate logistic regression analyses were used to screen out high-risk factors and establish a nomogram model. Concordance index (C-index), the receiver operating characteristic (ROC) curve, calibration curve, and the bootstrap method were used to evaluate the discrimination and calibration abilities of the nomogram.  Results  There were significant differences between the two groups in age, HBV DNA load, alanine aminotransferase, aspartate aminotransferase (AST), and platelet count (PLT) (t=-7.071, Z=-4.924, -3.693, -6.945, -0.585 and -5.723, all P < 0.001). The logistic regression analysis showed that age (odds ratio [OR]=1.074, 95% confidence interval [CI]: 1.043-1.107, P < 0.001), HBV DNA load (OR=0.442, 95%CI: 0.314-0.624, P < 0.001), AST(OR=1.096, 95%CI: 1.051-1.142, P < 0.001), and PLT(OR=0.992, 95%CI: 0.986-0.998, P=0.006) were high-risk factors for significant liver injury. The nomogram model established based on the above factors had a C-index of 0.845 in predicting significant liver injury and had a well-fitted calibration curve, with an area under the ROC curve (AUC) of 0.845 (95%CI: 0.795-0.895), which was significantly better than aspartate aminotransferase-to-platelet ratio index (AUC=0.781, 95%CI: 0.723-0.840) and fibrosis-4(AUC=0.802, 95%CI: 0.746-0.859).  Conclusion  There is a high proportion of IT-CHB patients with significant liver injury. The nomogram model established based on age, HBV DNA, AST, and PLT has a good predictive accuracy and can be used to predict significant liver injury in IT-CHB patients individually, reduce the need for liver biopsy, and provide a reference for precise antiviral treatment.

     

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    • References(29)
  • [1]
    Chinese Society of Infectious Diseases, Chinese Medical Association, Chinese Society of Infectious Diseases, Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B (version 2019)[J]. J Clin Hepatol, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007.

    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(2019年版)[J]. 临床肝胆病杂志, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007.
    [2]
    TERRAULT NA, LOK A, MCMAHON BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance[J]. Hepatology, 2018, 67(4): 1560-1599. DOI: 10.1002/hep.29800.
    [3]
    SARIN SK, KUMAR M, LAU GK, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: A 2015 update[J]. Hepatol Int, 2016, 10(1): 1-98. DOI: 10.1007/s12072-015-9675-4.
    [4]
    European Association for the Study of the Liver. EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection[J]. J Hepatol, 2017, 67(2): 370-398. DOI: 10.1016/j.jhep.2017.03.021.
    [5]
    GAO HY, LIU N, LI CX, et al. Clinical features and liver histopathological analysis of patients in the immune tolerance stage of chronic hepatitis B virus infection[J]. Chin Hepatol, 2018, 23(2): 136-139. DOI: 10.14000/j.cnki.issn.1008-1704.2018.02.012.

    高红艳, 刘娜, 李春霞, 等. 慢性乙型肝炎病毒感染者免疫耐受期的临床特征与肝组织病理学分析[J]. 肝脏, 2018, 23(2): 136-139. DOI: 10.14000/j.cnki.issn.1008-1704.2018.02.012.
    [6]
    XING YF, ZHOU DQ, HE JS, et al. Clinical and histopathological features of chronic hepatitis B virus infected patients with high HBV DNA viral load and normal alanine aminotransferase level: A multicentre-based study in China[J]. PLoS One, 2018, 13(9): e0203220. DOI: 10.1371/journal.pone.0203220.
    [7]
    KUMAR M, SARIN SK, HISSAR S, et al. Virologic and histologic features of chronic hepatitis B virus-infected asymptomatic patients with persistently normal ALT[J]. Gastroenterology, 2008, 134(5): 1376-1384. DOI: 10.1053/j.gastro.2008.02.075.
    [8]
    NGUYEN MH, GARCIA RT, TRINH HN, et al. Histological disease in Asian-Americans with chronic hepatitis B, high hepatitis B virus DNA, and normal alanine aminotransferase levels[J]. Am J Gastroenterol, 2009, 104(9): 2206-2213. DOI: 10.1038/ajg.2009.248.
    [9]
    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]. PLoS One, 2012, 7(2): e32622. DOI: 10.1371/journal.pone.0032622.
    [10]
    KIM HL, KIM GA, PARK JA, et al. Cost-effectiveness of antiviral treatment in adult patients with immune-tolerant phase chronic hepatitis B[J]. Gut, 2020. [Online ahead of print]. DOI: 10.1136/gutjnl-2020-321309.
    [11]
    KIM GA, LIM YS, HAN S, et al. High risk of hepatocellular carcinoma and death in patients with immune-tolerant-phase chronic hepatitis B[J]. Gut, 2018, 67(5): 945-952. DOI: 10.1136/gutjnl-2017-314904.
    [12]
    GAO HY, LIU N, LI CX, et al. Research advances in influencing factors for natural prognosis of patients with chronic HBV infection in immune tolerance phase[J]. J Clin Hepatol, 2017, 33(8): 1572-1575. DOI: 10.3969/j.issn.1001-5256.2017.08.035.

    高红艳, 刘娜, 李春霞, 等. 慢性HBV感染者免疫耐受期自然转归相关影响因素的研究进展[J]. 临床肝胆病杂志, 2017, 33(8): 1572-1575. DOI:10. 3969/j.issn.1001-5256.2017.08.035.
    [13]
    ZHOU LL, LIU N, LI CX, et al. Research advances in the diagnosis and treatment of patients in the immune tolerance stage of chronic hepatitis B virus infection[J]. J Clin Hepatol, 2019, 35(8): 1824-1827. DOI: 10.3969/j.issn.1001-5256.2019.08.039.

    周路路, 刘娜, 李春霞, 等. 慢性HBV感染免疫耐受期诊治进展[J]. 临床肝胆病杂志, 2019, 35(8): 1824-1827. DOI: 10.3969/j.issn.1001-5256.2019.08.039.
    [14]
    LIU M, ZUO LL, ZHANG RY, et al. Research progress of antiviral therapy in patients with chronic HBV infection in immune tolerance phase[J]. Chin J Infect Dis, 2020, 38(11): 750-752. DOI: 10.3760/cma.j.cn311365-20190422-00138.

    刘敏, 左丽丽, 张茹薏, 等. 乙型肝炎免疫耐受期患者进行抗病毒治疗的研究进展[J]. 中华传染病杂志, 2020, 38(11): 750-752. DOI: 10.3760/cma.j.cn311365-20190422-00138.
    [15]
    ZHUANG H. Should patients in the immune tolerance stage of chronic hepatitis B virus infection be treated?[J]. J Clin Hepatol, 2021, 37(2): 272-277. DOI: 10.3969 /j.issn.1001-5256.2021.02.007.

    庄辉. 慢性HBV感染免疫耐受期应否治疗?[J]. 临床肝胆病杂志, 2021, 37(2): 272-277. DOI: 10.3969 /j.issn.1001-5256.2021.02.007.
    [16]
    LOK AS, MCMAHON BJ, BROWN RS Jr, et al. Antiviral therapy for chronic hepatitis B viral infection in adults: A systematic review and meta-analysis[J]. Hepatology, 2016, 63(1): 284-306. DOI: 10.1002/hep.28280.
    [17]
    LEE HW, CHON YE, KIM BK, et al. Negligible HCC risk during stringently defined untreated immune-tolerant phase of chronic hepatitis B[J]. Eur J Intern Med, 2021, 84: 68-73. DOI: 10.1016/j.ejim.2020.10.022.
    [18]
    KLAIR JS, VANCURA J, MURALI AR. PRO: Patients with chronic hepatitis B in immune-tolerant phase should be treated[J]. Clin Liver Dis (Hoboken), 2020, 15(1): 21-24. DOI: 10.1002/cld.892.
    [19]
    ROCKEY DC, CALDWELL SH, GOODMAN ZD, et al. Liver biopsy[J]. Hepatology, 2009, 49(3): 1017-1044. DOI: 10.1002/hep.22742.
    [20]
    Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association. The guideline of prevention and treatment for chronic hepatitis B(2015 version)[J]. J Clin Hepatol, 2015, 31(12): 1941-1960. DOI: 10.3969/j.issn.1001-5256.2015.12.002.

    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年版)[J]. 临床肝胆病杂志, 2015, 31(12): 1941-1960. DOI: 10. 3969 /j. issn. 1001-5256. 2015. 12. 002.
    [21]
    ZHUANG H. Correction note on the estimated number of patients in the immune － tolerant phase of hepatitis B virus infection in China and globally[J]. J Clin Hepatol, 2021, 37(4): 785-786. DOI: 10.3969 /j.issn.1001-5256.2021.04.012.

    庄辉. 全球和我国HBV感染免疫耐受期患者人数估计更正说明[J]. 临床肝胆病杂志, 2021, 37(4): 785-786. DOI: 10.3969/j.issn.1001-5256.2021.04.012
    [22]
    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. DOI: 10.1016/S2468-1253(18)30056-6.
    [23]
    BERTOLETTI A, KENNEDY PT. The immune tolerant phase of chronic HBV infection: New perspectives on an old concept[J]. Cell Mol Immunol, 2015, 12(3): 258-263. DOI: 10.1038/cmi.2014.79.
    [24]
    LIAW YF, CHU CM. Immune tolerance phase of chronic hepatitis B[J]. Gastroenterology, 2017, 152(5): 1245-1246. DOI: 10.1053/j.gastro.2016.11.057.
    [25]
    KENNEDY PTF, BERTOLETTI A, MASON WS. Reply to immune tolerance phase of chronic hepatitis B[J]. Gastroenterology, 2017, 152(5): 1246-1247. DOI: 10.1053/j.gastro.2017.03.002.
    [26]
    WANG H, XUE L, YAN R, et al. Comparison of FIB-4 and APRI in Chinese HBV-infected patients with persistently normal ALT and mildly elevated ALT[J]. J Viral Hepat, 2013, 20(4): e3-e10. DOI: 10.1111/jvh.12010.
    [27]
    FATTOVICH G, BORTOLOTTI F, DONATO F. Natural history of chronic hepatitis B: Special emphasis on disease progression and prognostic factor[J]. J Hepatol, 2008, 48(2): 335-352. DOI: 10.1016/j.jhep.2007.11.011.
    [28]
    RAFFETTI E, FATTOVICH G, DONATO F. Incidence of hepatocellular carcinoma in untreated subjects with chronic hepatitis B: A systematic review and meta-analysis[J]. Liver Int, 2016, 36(9): 1239-1251. DOI: 10.1111/liv.13142.
    [29]
    ILOEJE UH, YANG HI, SU J, et al. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load[J]. Gastroenterology, 2006, 130(3): 678-686. DOI: 10.1053/j.gastro.2005.11.016.
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