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Volume 38 Issue 9
Sep.  2022
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Article Navigation >  Journal of Clinical Hepatology  > 2022  >  38(9): 2005-2009

Influencing factors for liver inflammation and fibrosis in the immune-tolerant phase of HBV infection

DOI: 10.3969/j.issn.1001-5256.2022.09.012

  • Department of Hepatology, Yunnan Provincial Clinical Medical Center for Infectious Diseases, The Third People's Hospital of Kunming, Kunming 650041, China

Research funding:

Yunnan Provincial Department of Science and Technology Applied Basic Research Project (2017FH001-88)

More Information
  • Corresponding author: LIU Li, liuli197210@163.com(ORCID: 0000-0001-7712-4931)
  • Received Date: 2022-01-16
  • Accepted Date: 2022-03-07
  • Published Date: 2022-09-20
    Abstract
  •   Objective  To evaluate the degree of liver injury and liver fibrosis in patients in the immune-tolerant phase of chronic HBV infection, and to provide a basis for judging the condition of patients in the immune-tolerant phase.  Methods  A total of 300 patients with HBV DNA ≥107 IU/mL, alanine aminotransferase (ALT) ≤40 U/L, and complete data who were treated in The Third People's Hospital of Kunming from January 2015 to December 2019 were enrolled as subjects, and related data were collected, including age, sex, duration of HBV infection, blood biochemistry, hepatitis B surface antigen (HBsAg) level, and HBV DNA. Liver pathological examination was performed for all patients, and the patients were divided into G < 2 and G ≥2 groups according to inflammation grade and S < 2 and S ≥2 groups according to the degree of fibrosis. The t-test was used for comparison of continuous data between two groups, and univariate and multivariate unconditional logistic regression analyses were used to investigate the influencing factors for G ≥2 liver inflammation and S ≥2 liver fibrosis.  Results  Among the 300 patients, 213 (71%) had G ≥2 liver inflammation and 120 (40%) had S ≥2 liver fibrosis, with a baseline age of 26.06±9.01 years; male patients accounted for 48%, and the duration of infection was 5.62±5.09 years. The univariate analysis showed that there were significant differences between the G < 2 and G ≥2 groups in ALT, alkaline phosphatase (ALP), albumin (Alb), platelet count (PLT), diameter of the portal vein, and spleen thickness (t=-26.677, -11.612, 2.149, 5.410, -6.092, and -2.911, all P < 0.05), and there were significant differences between the S < 2 and S ≥2 groups in duration of infection, ALT, ALP, Alb, HBV DNA, PLT, diameter of the portal vein, and spleen thickness (t=-6.320, -6.694, -7.880, 2.349, 4.552, 19.160, -5.782, and -5.622, all P < 0.05). The multivariate analysis showed that ALT (odds ratio [OR]=10.270, 95% confidence interval [CI]: 2.212-47.672, P=0.003) and ALP (OR=1.097, 95%CI: 1.013-1.188, P=0.023) were independent risk factors for G ≥2 liver inflammation in patients in the immune-tolerant phase, and ALP (OR=1.034, 95%CI: 1.015-1.054, P < 0.001), PLT (OR=0.913, 95%CI: 0.886-0.938, P < 0.001), HBV DNA (OR=0.198, 95%CI: 0.062-0.636, P=0.007), and duration of infection (OR=1.176, 95%CI: 1.033-1.340, P=0.015) were independent influencing factors for S ≥2 liver fibrosis in patients in the immune-tolerant phase.  Conclusion  Most patients in the immune-tolerant phase have significant liver histological changes. ALT and ALP are the influencing factors for significant liver inflammation, and ALP, HBV-DNA, PLT, and infection time are the influencing factors for significant liver fibrosis in patients in the immune-tolerant phase.

     

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    • References(26)
  • [1]
    TACHTATZIS PM, MARSHALL A, ARAVINTHAN A, et al. Correction: chronic hepatitis B virus infection: The relation between hepatitis B antigen expression, telomere length, senescence, inflammation and fibrosis[J]. PLoS One, 2015, 10(7): e0134315. DOI: 10.1371/journal.pone.0134315.
    [2]
    CHEN JD, ZHAI RR, LIU C, et al. Study on the correlation between serum core antibody of hepatitis B virus and glutamic pyruvic transaminase and nucleic acid copy number of hepatitis B virus in patients with chronic hepatitis B cirrhosis[J]. Clin J Med Offic, 2021, 49(8): 906-907. DOI: 10.16680/j.1671-3826.2021.08.18.

    陈家东, 翟荣荣, 刘灿, 等. 慢性乙肝肝硬化患者血清乙肝病毒核心抗体定量与谷丙转氨酶、乙肝病毒核酸拷贝数相关性研究[J]. 临床军医杂志, 2021, 49(8): 906-907. DOI: 10.16680/j.1671-3826.2021.08.18.
    [3]
    LEE HA, LEE HW, KIM IH, et al. Extremely low risk of hepatocellular carcinoma development in patients with chronic hepatitis B in immune-tolerant phase[J]. Aliment Pharmacol Ther, 2020, 52(1): 196-204. DOI: 10.1111/apt.15741.
    [4]
    CHEN Y, LI X, YE B, et al. Effect of telbivudine therapy on the cellular immune reponse in chronic hepatitis B[J]. Antiviral Res, 2011, 91: 23-31. DOI: 10.1016/j.antiviral.2011.04.008.
    [5]
    European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B virus infection[J]. J Hepatol, 2012, 57(1): 167-185. DOI: 10.1016/j.jhep.2012.02.010.
    [6]
    TRAN TT. Immune tolerant hepatitis B: a clinical dilemma[J]. Gastroenterol Hepatol (N Y), 2011, 7(8): 511-516. http://pdfs.semanticscholar.org/8cb9/7b4485e5ffef5819f2a569a08aeeca4fc4d1.pdf
    [7]
    ZONG L. Liver immune tolerance and HBV-induced liver cancer[D]. Hefei: University of Science and Technology of China, 2018.

    宗璐. 肝脏免疫耐受与HBV诱发肝癌[D]. 合肥: 中国科学技术大学, 2018.
    [8]
    Chinese Society of Infectious Diseases, Chinese Medical Association; Chinese Society of Hepatology, 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.

    中华医学会感染病学分会, 中华医学会肝病学分会. 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.
    [9]
    NONG CL, LONG TH, GUO J. Histological characteristics and clinical analysis of chronic hepatitis B liver with normal ALT[J]. Shandong Med, 2012, 52(7): 51-53. DOI: 10.3969/j.issn.1002-266X.2012.07.020.

    农村立, 龙腾河, 郭堑. ALT正常的慢性乙型肝炎肝组织学特点与临床分析[J]. 山东医药, 2012, 52(7): 51-53. DOI: 10.3969/j.issn.1002-266X.2012.07.020.
    [10]
    GONG X, YANG J, TANG J, et al. A mechanistic assessment of the discordance between normal serum alanine aminotransferase levels and altered liver histology in chronic hepatitis B[J]. PLoS One, 2015, 10(7): e0134532. DOI: 10.1371/journal.pone.0134532.
    [11]
    WANG H, RU GQ, YAN R, et al. Histologic disease in Chinese chronic hepatitis B patients with low viral loads and persistently normal alanine aminotransferase levels[J]. J Clin Gastroenterol, 2016, 50(9): 790-796. DOI: 10.1097/MCG.0000000000000544.
    [12]
    ZHOU X, LI WZ, MA WT, et al. Correlation between liver histopathology and age, ALT and HBV DNA levels in patients with normal ALT and chronic HBV infection[J]. Chin Hepatol, 2019, 24(10): 1141-1144. DOI: 10.3969/j.issn.1008-1704.2019.10.016.

    周璇, 李维正, 马文婷, 等. ALT正常慢性HBV感染者肝组织病理与年龄、ALT和HBV DNA水平相关性研究[J]. 肝脏, 2019, 24(10): 1141-1144. DOI: 10.3969/j.issn.1008-1704.2019.10.016.
    [13]
    GUI HL, WANG H, YANG YH, et al. Significant histopathology in Chinese chronic hepatitis B patients with persistently high-normal alanine aminotransferase[J]. J Viral Hepat, 2010, 17 (Suppl 1): 44-50. DOI: 10.1111/j.1365-2893.2010.01270.x.
    [14]
    GÖBEL T, ERHARDT A, HERWIG M, et al. High prevalence of significant liver fibrosis and cirrhosis in chronic hepatitis B patients with normal ALT in central Europe[J]. J Med Virol, 2011, 83(6): 968-973. DOI: 10.1002/jmv.22048.
    [15]
    PARK JY, PARK YN, KIM DY, et al. High prevalence of significant histology in asymptomatic chronic hepatitis B patients with genotype C and high serum HBV DNA levels[J]. J Viral Hepat, 2008, 15(8): 615-621. DOI: 10.1111/j.1365-2893.2008.00989.x.
    [16]
    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.
    [17]
    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.
    [18]
    WANG C, DEUBNER H, SHUHART M, et al. High prevalence of significant fibrosis in patients with immunotolerance to chronic hepatitis B infection: (abstract)[J]. Hepatology, 2005, 42 (Suppl 1): 573A.
    [19]
    LIAO B, WANG Z, LIN S, et al. Significant fibrosis is not rare in Chinese chronic hepatitis B patients with persistent normal ALT[J]. PLoS One, 2013, 8(10): e78672. DOI: 10.1371/journal.pone.0078672.
    [20]
    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.
    [21]
    HUANG Y. Patients in the immune-tolerant phase of chronic HBV infection should be actively treated with antiviral therapy[J]. J Clin Hepatol, 2021, 37(5): 1026. DOI: 10.3969/j.issn.1001-5256.2021.05.008.

    黄缘. 慢性HBV感染免疫耐受期患者应积极抗病毒治疗[J]. 临床肝胆病杂志, 2021, 37(5): 1026. DOI: 10.3969/j.issn.1001-5256.2021.05.008.
    [22]
    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.
    [23]
    XING HQ, XIN SJ, ZHANG X, et al. Clinicopathological characteristics of patients with chronic hepatitis B virus infection in immune tolerance stage[J]. World Chin J Dig, 2006, 14(14): 1425-1429. DOI: 10.3969/j.issn.1009-3079.2006.14.018.

    邢汉前, 辛绍杰, 张欣, 等. 慢性乙型肝炎病毒感染免疫耐受期患者的临床病理特征[J]. 世界华人消化杂志, 2006, 14(14): 1425-1429. DOI: 10.3969/j.issn.1009-3079.2006.14.018.
    [24]
    LIN CL, LIAO LY, LIU CJ, et al. Hepatitis B viral factors in HBeAg-negative carriers with persistently normal serum alanine aminotransferase levels[J]. Hepatology, 2007, 45(5): 1193-1198. DOI: 10.1002/hep.21585.
    [25]
    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.
    [26]
    LIN Y, LI X. Research status of platelets in chronic liver disease[J]. J Clin Hepatol, 2017, 33(11): 2243-2246. DOI: 10.3969/j.issn.1001-5256.2017.11.043.

    林岩, 李汛. 血小板在慢性肝病中的研究现状[J]. 临床肝胆病杂志, 2017, 33(11): 2243-2246. DOI: 10.3969/j.issn.1001-5256.2017.11.043.
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