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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 39 Issue 3
Mar.  2023
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Article Contents

Role of new serological markers in evaluating the progression of liver disease in patients with chronic HBV infection and normal aminotransferases

DOI: 10.3969/j.issn.1001-5256.2023.03.026
Research funding:

Yunnan Province High-level Health Talent Project (H-2017071);

Yunnan Provincial Department of Education Research Fund (2021J0239)

More Information
  • Corresponding author: LIU Huaie, liuhuaie@163.com (ORCID: 0000-0003-0962-2474)
  • Received Date: 2022-07-12
  • Accepted Date: 2022-09-02
  • Published Date: 2023-03-20
  • Antiviral therapy is the basic treatment method for improving prognosis recommended in the management guidelines of chronic hepatitis B in China and globally. For patients with chronic HBV infection and normal transaminases, it is difficult in clinical practice to accurately evaluate the progression of hepatitis and identify suitable patients who need antiviral therapy. In order to objectively and accurately evaluate the degree of liver inflammatory activity in such patients, more and more noninvasive evaluation indicators have been used in addition to conventional liver biopsy. This article reviews the new serological indicators that can reflect the degree of liver inflammation and/or fibrosis in patients with chronic HBV infection and normal aminotransferase levels, hoping to provide a reference for antiviral decision-making in these patients.

     

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  • [1]
    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. CHB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]. Clin Liver Dis (Hoboken), 2018, 12(1): 33-34. DOI: 10.1002/cld.728.
    [3]
    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.
    [4]
    CHEN JD, ZHAI RR, LIU C, et al. Study on the correlation between serum HBV core antibody and Alanine transaminase and HBV DNA copy number 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.
    [5]
    WANG J, YAN X, CHEN Y, et al. Characteristics of hepatitis B core antibody level in the natural history of chronic hepatitis B[J]. Discov Med, 2018, 26(143): 119-125.
    [6]
    ZHOU J, SONG L, ZHAO H, et al. Serum hepatitis B core antibody as a biomarker of hepatic inflammation in chronic hepatitis B patients with normal alanine aminotransferase[J]. Sci Rep, 2017, 7(1): 2747. DOI: 10.1038/s41598-017-03102-3.
    [7]
    WU Z, DONG X, WANG G, et al. Clinical noninvasive markers for antiviral therapy decision in chronic hepatitis B with alanine aminotransferase less than two times upper limit of normal[J]. J Viral Hepat, 2019, 26(2): 287-296. DOI: 10.1111/jvh.13030.
    [8]
    CHEN LY, QI CX, AN WN, et al. Levels and predictive value of HBcrAg in CHB patients with HBeAg positive in treatment with entecavir[J/CD]. Chin J Liver Dis (Electronic Version), 2022, 14(2): 50-56. DOI: 10.3969/j.issn.1674-7380.2022.02.008.

    陈来印, 齐聪幸, 安伟娜, 等. HBeAg阳性CHB患者恩替卡韦治疗中HBcrAg水平变化及其对疗效预测价值[J/CD]. 中国肝脏病杂志(电子版), 2022, 14(2): 50-56. DOI: 10.3969/j.issn.1674-7380.2022.02.008.
    [9]
    WONG DK, TANAKA Y, LAI CL, et al. Hepatitis B virus core-related antigens as markers for monitoring chronic hepatitis B infection[J]. J Clin Microbiol, 2007, 45(12): 3942-3947. DOI: 10.1128/JCM.00366-07.
    [10]
    ZHANG ZQ, SHI BS, LU W, et al. Quantitative HBcrAg and HBcAb versus HBsAg and HBV DNA in predicting liver fibrosis levels of chronic hepatitis B patients[J]. Gastroenterol Hepatol, 2020, 43(9): 526-536. DOI: 10.1016/j.gastrohep.2020.03.017.
    [11]
    ZHANG ZQ, LU W, WANG YB, et al. Measurement of the hepatitis B core-related antigen is valuable for predicting the pathological status of liver tissues in chronic hepatitis B patients[J]. J Virol Methods, 2016, 235: 92-98. DOI: 10.1016/j.jviromet.2016.05.016.
    [12]
    TADA T, KUMADA T, TOYODA H, et al. Hepatitis B virus core-related antigen levels predict progression to liver cirrhosis in hepatitis B carriers[J]. J Gastroenterol Hepatol, 2018, 33(4): 918-925. DOI: 10.1111/jgh.13989.
    [13]
    CHEN EQ, TANG H. A promising new HBV serum marker—HBcrAg[J]. J Clin Hepatol, 2019, 35(10): 2159-2162. DOI: 10.3969/j.issn.1001-5256.2019.10.006.

    陈恩强, 唐红. 一种有前途的新型HBV血清标志物——HBcrAg[J]. 临床肝胆病杂志, 2019, 35(10): 2159-2162. DOI: 10. 3969/j. issn. 1001-5256. 2019. 10. 006.
    [14]
    WANG J, YU Y, LI G, et al. Relationship between serum HBV-RNA levels and intrahepatic viral as well as histologic activity markers in entecavir-treated patients[J]. J Hepatol, 2017. DOI: 10.1016/j.jhep.2017.08.021.[Online ahead of print]
    [15]
    HUANG CL, QI X, XU W, et al. Diagnostic value of serum hepatitis B virus RNA for significant inflammation in patients with chronic hepatitis B with normal or slightly elevated alanine aminotransferase[J]. Chin J Infect, 2020, 38(9): 569-574. DOI: 10.3760/cma.j.cn311365-20191217-00515.

    黄晨璐, 戚勋, 许伟, 等. 血清乙型肝炎病毒RNA对丙氨酸转氨酶正常或轻度升高的CHB患者显著性炎症的诊断价值[J]. 中华传染病杂志, 2020, 38(9): 569-574. DOI: 10.3760/cma.j.cn311365-20191217-00515.
    [16]
    LU FM, ZHANG Y. Application of serum Golgi glycoprotein 73 in the diagnosis of liver cirrhosis and its related mechanism[J]. J Clin Hepatol, 2018, 26(5): 321-324. DOI: 10.3969/j.issn.1001-5256.

    鲁凤民, 张芸. 血清高尔基体糖蛋白73在肝硬化诊断中的应用及其相关机制[J]. 中华肝脏病杂志, 2018, 26(5): 321-324. DOI: 10.3969/j.issn.1001-5256.
    [17]
    CAO Z, LI Z, WANG Y, et al. Assessment of serum Golgi protein 73 as a biomarker for the diagnosis of significant fibrosis in patients with chronic HBV infection[J]. J Viral Hepat, 2017, 24 (Suppl 1): 57-65. DOI: 10.1111/jvh.12786.
    [18]
    GATSELIS NK, TORNAI T, SHUMS Z, et al. Golgi protein-73: A biomarker for assessing cirrhosis and prognosis of liver disease patients[J]. World J Gastroenterol, 2020, 26(34): 5130-5145. DOI: 10.3748/wjg.v26.i34.5130.
    [19]
    WEI M, XU Z, PAN X, et al. Serum GP73 - an additional biochemical marker for liver inflammation in chronic HBV infected patients with normal or slightly raised ALT[J]. Sci Rep, 2019, 9(1): 1170. DOI: 10.1038/s41598-018-36480-3.
    [20]
    YAO M, WANG L, YOU H, et al. Serum GP73 combined AST and GGT reflects moderate to severe liver inflammation in chronic hepatitis B[J]. Clin Chim Acta, 2019, 493: 92-97. DOI: 10.1016/j.cca.2019.02.019.
    [21]
    MIYAAKI H, ICHIKAWA T, KAMO Y, et al. Significance of serum and hepatic microRNA-122 levels in patients with non-alcoholic fatty liver disease[J]. Liver Int, 2014, 34(7): e302-e307. DOI: 10.1111/liv.12429.
    [22]
    FANG Q, CHEN W, JIAN Y, et al. Serum expression level of MicroRNA-122 and its significance in patients with hepatitis B virus infection[J]. J Healthc Eng, 2022, 2022: 8430276. DOI: 10.1155/2022/8430276.
    [23]
    CHENG JL, ZHAO H, YANG SG, et al. Plasma miRNA-122-5p and miRNA-151a-3p identified as potential biomarkers for liver injury among CHB patients with PNALT[J]. Hepatol Int, 2018, 12(3): 277-287. DOI: 10.1007/s12072-018-9871-0.
    [24]
    GAO M, LIU R, ZHANG Q. The predictive value of serum mirna-122 and Wisteria multiflora lectin positive Mac-2 binding protein on the degree of liver fibrosis in patients with chronic viral hepatitis[J] J Clin Hepatol, 2018, 34(4): 764-769. DOI: 10.3969/J.issn.1001-5256,2018.04.014.

    高敏, 刘蓉, 张庆. 血清miRNA-122和紫藤多花凝集素阳性Mac-2结合蛋白对慢性病毒性肝炎患者肝纤维化程度的预测价值[J]. 临床肝胆病杂志, 2018, 34(4): 764-769. DOI: 10.3969/J.issn.1001-5256,2018.04.014.
    [25]
    KUNO A, IKEHARA Y, TANAKA Y, et al. A serum "sweet-doughnut" protein facilitates fibrosis evaluation and therapy assessment in patients with viral hepatitis[J]. Sci Rep, 2013, 3: 1065. DOI: 10.1038/srep01065.
    [26]
    URA K, FURUSYO N, OGAWA E, et al. Serum WFA(+) -M2BP is a non-invasive liver fibrosis marker that can predict the efficacy of direct-acting anti-viral-based triple therapy for chronic hepatitis C[J]. Aliment Pharmacol Ther, 2016, 43(1): 114-124. DOI: 10.1111/apt.13431.
    [27]
    KAMADA Y, ONO M, HYOGO H, et al. Use of Mac-2 binding protein as a biomarker for nonalcoholic fatty liver disease diagnosis[J]. Hepatol Commun, 2017, 1(8): 780-791. DOI: 10.1002/hep4.1080.
    [28]
    FENG S, WANG Z, ZHAO Y, et al. Wisteria floribunda agglutinin-positive Mac-2-binding protein as a diagnostic biomarker in liver cirrhosis: an updated meta-analysis[J]. Sci Rep, 2020, 10(1): 10582. DOI: 10.1038/s41598-020-67471-y.
    [29]
    MAK LY, WONG DK, CHEUNG KS, et al. Role of Serum M2BPGi levels in predicting persistence of advanced fibrosis in chronic hepatitis B virus infection[J]. Dig Dis Sci, 2022, 67(11): 5127-5136. DOI: 10.1007/s10620-022-07429-4.
    [30]
    MUSHTAQ S, GHANI E, AZAM K, et al. Comparison of chitinase-3-like protein 1, aspartate aminotransferase-to-platelet ratio index, and fibrosis-4 index with shear-wave elastography[J]. Eur J Gastroenterol Hepatol, 2019, 31(3): 357-362. DOI: 10.1097/MEG.0000000000001291.
    [31]
    JIANG Z, WANG S, JIN J, et al. The clinical significance of serum chitinase 3-like 1 in hepatitis B-related chronic liver diseases[J]. J Clin Lab Anal, 2020, 34(5): e23200. DOI: 10.1002/jcla.23200.
    [32]
    HUANG H, WU T, MAO J, et al. CHI3L1 is a liver-enriched, noninvasive biomarker that can be used to stage and diagnose substantial hepatic fibrosis[J]. OMICS, 2015, 19(6): 339-345. DOI: 10.1089/omi.2015.0037.
    [33]
    YAN L, DENG Y, ZHOU J, et al. Serum YKL-40 as a biomarker for liver fibrosis in chronic hepatitis B patients with normal and mildly elevated ALT[J]. Infection, 2018, 46(3): 385-393. DOI: 10.1007/s15010-018-1136-2.
    [34]
    ZHOU C, CHENG H, QIN W, et al. Pygopus2 inhibits the efficacy of paclitaxel-induced apoptosis and induces multidrug resistance in human glioma cells[J]. Oncotarget, 2017, 8(17): 27915-27928. DOI: 10.18632/oncotarget.15843.
    [35]
    ZHU CL, ZHU TT, WANG K, et al. Evaluation value of serum Pygo2 level in patients with chronic hepatitis C on the degree of liver fibrosis[J]. J Prac Hepatol, 2017, 20(2): 161-164. DOI: 10.3969/j.issn.1672-5069.2017.02.009.

    朱传龙, 朱甜甜, 王坤, 等. 慢性丙型肝炎患者血清Pygo2水平对肝纤维化程度的评估价值探讨[J]. 实用肝脏病杂志, 2017, 20(2): 161-164. DOI: 10.3969/j.issn.1672-5069.2017.02.009.
    [36]
    YU LH, WANG H, QIN L, et al. Expression of m2bpgi in serum of patients with chronic hepatitis B liver fibrosis and its combined diagnostic value[J]. J Med Sci Cent South China, 2021, 49(2): 197-202. DOI: 10. 15972/j. cnki.43-1509/r. 2021. 02. 016.

    于丽华, 王宏, 秦丽, 等. Pygo2、M2BPGi在CHB肝纤维化患者血清中的表达及联合诊断价值[J]. 中南医学科学杂志, 2021, 49(2): 197-202. DOI: 10. 15972/j. cnki.43-1509/r. 2021. 02. 016.
    [37]
    LIN L, SHEN M, RUAN JW. Expression of programmed death receptor 1 in liver tissue of patients with autoimmune hepatitis and its clinical significance[J]. J Prac Hepatol, 2019, 22(2): 204-207. DOI: 10.3969/j.issn.1672-5069.2019.02.013.

    林兰, 沈敏, 阮健文. 自身免疫性肝炎患者肝组织程序性死亡受体1表达及其临床意义探讨[J]. 实用肝脏病杂志, 2019, 22(2): 204-207. DOI: 10.3969/j.issn.1672-5069.2019.02.013.
    [38]
    YANG M, DOU WW, SUN GH, et al. Programmed cell death-1 in patients with primary liver cancer and its effect on prognosis[J]. J Buon, 2019, 24(3): 1167-1174.
    [39]
    DENG M, WU YH, DING RY, et al. Study on the correlation between peripheral blood PD-1, PD-L1, M30, M65 and liver inflammation in hepatitis B virus carriers[J]. Preventive Med, 2020, 32(12): 1242-1245. DOI: 10.19485/j.cnki.issn2096-5087.2020.12.013.

    邓敏, 吴云辉, 丁韧烨, 等. 乙型肝炎病毒携带者外周血PD-1、PD-L1、M30、M65与肝脏炎症的相关性研究[J]. 预防医学, 2020, 32(12): 1242-1245. DOI: 10.19485/j.cnki.issn2096-5087.2020.12.013.
    [40]
    RUJEERAPAIBOON N, TANTIWORAWIT A, PIRIYAKHUNTORN P, et al. Correlation between serum ferritin and viral hepatitis in thalassemia patients[J]. Hemoglobin, 2021, 45(3): 175-179. DOI: 10.1080/03630269.2021.1926277.
    [41]
    QI NX, WEI LJ. Changes of serum ferritin (SF) level in patients with chronic hepatitis B cirrhosis and its clinical value[J]. Chin Hepatol, 2019, 24(4): 471-472. DOI: 10.14000/j.cnki.issn.1008-1704.2019.04.043.

    齐宁霞, 韦丽娟. CHB肝硬化患者血清铁蛋白(SF)水平变化及其临床价值[J]. 肝脏, 2019, 24(4): 471-472. DOI: 10.14000/j.cnki.issn.1008-1704.2019.04.043.
    [42]
    YAN Y, LI XQ. Value analysis of constructing a combined detection factor model for the diagnosis of primary liver cancer based on logistic regression analysis[J]. Internal Med China, 2021, 16(5): 602-607. DOI: 10.16121/j.cnki.cn45-1347/r.2021.05.11.

    闫圆, 李小全. 基于Logistic回归分析构建联合检测因子模型诊断原发性肝癌的价值分析[J]. 内科, 2021, 16(5): 602-607. DOI: 10.16121/j.cnki.cn45-1347/r.2021.05.11.
    [43]
    YANG Q, LIU HE, YOU J, et al. Noninvasive diagnotisc mod- els for chronic hepatitis B liver fibrosis[J]. J Clin Hepatol, 2021, 37(10): 2420-2424. DOI: 10.3969/j.issn.1001-5256.2021.10.034.

    杨琴, 刘怀鄂, 游晶, 等. CHB肝纤维化的无创诊断模型[J]. 临床肝胆病杂志, 2021, 37(10): 2420-2424. DOI: 10.3969/j.issn.1001-5256.2021.10.034.
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