中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 39 Issue 8
Aug.  2023
Turn off MathJax
Article Contents
Article Navigation >  Journal of Clinical Hepatology  > 2023  >  39(8): 1769-1774

Should antiviral treatment be initiated for chronic hepatitis B patients with high-normal alanine aminotransferase?

DOI: 10.3969/j.issn.1001-5256.2023.08.001

  • Department of Microbiology and Center of Infectious Diseases, Peking University Health Science Center, Beijing 100191, China

More Information
  • Corresponding author: ZHUANG Hui, zhuangbmu@126.com (ORCID: 0000-0001-9119-6325)
  • Received Date: 2023-08-06
  • Accepted Date: 2023-08-07
  • Published Date: 2023-08-20
    Abstract
  • Current guidelines recommend antiviral treatment for chronic hepatitis B (CHB) patients with elevated alanine aminotransferase (ALT) and positive HBV DNA. However, more and more studies have shown that CHB patients with high-normal ALT 0.5 to 1 times the upper limit of normal have significant necroinflammation and/or fibrosis in the liver and the risk of progressive liver diseases such as liver cirrhosis, hepatocellular carcinoma, hepatitis B-related complications, and even death. This article discusses the definition of high-normal ALT and the clinical and virological features of CHB patients with high-normal ALT, as well as whether antiviral treatment should be initiated for such patients.

     

    • FullText(HTML)
  • loading
    • References(46)
  • [1]
    LIAW YF, KAO JH, PIRATVISUTH T, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update[J]. Hepatol Int, 2012, 6(3): 531-561. DOI: 10.1007/s12072-012-9365-4.
    [2]
    LIAW YF, LEUNG N, GUAN R, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2005 update[J]. Liver Int, 2005, 25(3): 472-489. DOI: 10.1111/j.1478-3231.2005.01134.x.
    [3]
    LOK AS, MCMAHON BJ. Chronic hepatitis B[J]. Hepatology, 2007, 45(2): 507-539. DOI: 10.1002/hep.21513.
    [4]
    LIAW YF, LEUNG N, KAO JH, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update[J]. Hepatol Int, 2008, 2(3): 263-283. DOI: 10.1007/s12072-008-9080-3.
    [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]
    World Health Organization. Global hepatitis report, 2017[R/OL]. Geneva, Switzerland: World Health Organization, 2017. https://www.who.int/publications/i/item/9789241565455.
    [7]
    Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Infectious Diseases, Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B (version 2022)[J]. Infect Dis Info, 2023, 36(1): 1-17. DOI: 10.3969/j.issn.1007-8134.2023.01.01.

    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(2022年版)[J]. 传染病信息, 2023, 36(1): 1-17. DOI: 10.3969/j.issn.1007-8134.2023.01.01.
    [8]
    Ministry of Health of the PRC. Reference intervals for common clinical biochemistry tests. Part 1: Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and γ-glutamyltansferase[S]. Beijing: Standards Press of China, 2012.

    中华人民共和国卫生部. WS/T 404.1—2012临床常用生化检验项目参考区间第1部分: 血清丙氨酸氨基转移酶、天门冬氨酸氨基转移酶、碱性磷酸酶和γ-谷氨酰基转移酶[S]. 北京: 中国标准出版社, 2012.
    [9]
    WANG BL, PAN BS. Differentiate between the reference interval and the clinical diagnosis and treatment decision threshold for alanine aminotransferase[J]. Chin J Hepatol, 2021, 29(12): 1213-1217. DOI: 10.3760/cma.j.cn501113-20211009-00495.

    王蓓丽, 潘柏申. ALT的参考区间与临床诊疗决策阈值的辨析[J]. 中华肝脏病杂志, 2021, 29(12): 1213-1217. DOI: 10.3760/cma.j.cn501113-20211009-00495.
    [10]
    KEEFFE EB, DIETERICH DT, HAN SH, et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2008 update[J]. Clin Gastroenterol Hepatol, 2008, 6(12): 1315-1341; quiz 1286. DOI: 10.1016/j.cgh.2008.08.021.
    [11]
    SARRI G, WESTBY M, BERMINGHAM S, et al. Diagnosis and management of chronic hepatitis B in children, young people, and adults: summary of NICE guidance[J]. BMJ, 2013, 346: f3893. DOI: 10.1136/bmj.f3893.
    [12]
    KAO JH, HU TH, JIA J, et al. East Asia expert opinion on treatment initiation for chronic hepatitis B[J]. Aliment Pharmacol Ther, 2020, 52(10): 1540-1550. DOI: 10.1111/apt.16097.
    [13]
    KWO PY, COHEN SM, LIM JK. ACG clinical guideline: evaluation of abnormal liver chemistries[J]. Am J Gastroenterol, 2017, 112(1): 18-35. DOI: 10.1038/ajg.2016.517.
    [14]
    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.
    [15]
    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.
    [16]
    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.
    [17]
    LAI M, HYATT BJ, NASSER I, et al. The clinical significance of persistently normal ALT in chronic hepatitis B infection[J]. J Hepatol, 2007, 47(6): 760-767. DOI: 10.1016/j.jhep.2007.07.022.
    [18]
    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.
    [19]
    DUAN M, CHI X, XIAO H, et al. High-normal alanine aminotransferase is an indicator for liver histopathology in HBeAg-negative chronic hepatitis B[J]. Hepatol Int, 2021, 15(2): 318-327. DOI: 10.1007/s12072-021-10153-2.
    [20]
    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.
    [21]
    NAKAZAWA T, SHIBUYA A, TAKEUCHI A, et al. Viral level is an indicator of long-term outcome of hepatitis B virus e antigen-negative carriers with persistently normal serum alanine aminotransferase levels[J]. J Viral Hepat, 2011, 18(7): e191-e199. DOI: 10.1111/j.1365-2893.2010.01427.x.
    [22]
    YUEN MF, YUAN HJ, WONG DK, et al. Prognostic determinants for chronic hepatitis B in Asians: therapeutic implications[J]. Gut, 2005, 54(11): 1610-1614. DOI: 10.1136/gut.2005.065136.
    [23]
    KIM HC, NAM CM, JEE SH, et al. Normal serum aminotransferase concentration and risk of mortality from liver diseases: prospective cohort study[J]. BMJ, 2004, 328(7446): 983. DOI: 10.1136/bmj.38050.593634.63.
    [24]
    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.
    [25]
    LI Q, LU C, LI W, et al. The independent predictors of significant liver histological changes in chronic hepatitis B virus infection patients with persistently high-normal or low-normal alanine transaminase levels[J]. Discov Med, 2017, 23(124): 19-25.
    [26]
    LI S, SHI LC, XU XQ, et al. Systematic review and metaanalysis: significant histological changes among treatment-naïve chronic hepatitis B patients with normal alanine aminotransferase levels by different criteria[J]. Aliment Pharmacol Ther, 2023. DOI: 10.1111/apt.17658.[Epub ahead of print].
    [27]
    LEE MH, YANG HI, LIU J, et al. Prediction models of long-term cirrhosis and hepatocellular carcinoma risk in chronic hepatitis B patients: risk scores integrating host and virus profiles[J]. Hepatology, 2013, 58(2): 546-554. DOI: 10.1002/hep.26385.
    [28]
    TSENG TC, LIU CJ, YANG HC, et al. High levels of hepatitis B surface antigen increase risk of hepatocellular carcinoma in patients with low HBV load[J]. Gastroenterology, 2012, 142(5): 1140-1149. e3; quiz e13-e14. DOI: 10.1053/j.gastro.2012.02.007.
    [29]
    YUEN MF, TANAKA Y, FONG DY, et al. Independent risk factors and predictive score for the development of hepatocellular carcinoma in chronic hepatitis B[J]. J Hepatol, 2009, 50(1): 80-88. DOI: 10.1016/j.jhep.2008.07.023.
    [30]
    ISHIGURO S, INOUE M, TANAKA Y, et al. Serum aminotransferase level and the risk of hepatocellular carcinoma: a population-based cohort study in Japan[J]. Eur J Cancer Prev, 2009, 18(1): 26-32. DOI: 10.1097/CEJ.0b013e3282fa9edd.
    [31]
    YANG HI, YEH SH, CHEN PJ, et al. Associations between hepatitis B virus genotype and mutants and the risk of hepatocellular carcinoma[J]. J Natl Cancer Inst, 2008, 100(16): 1134-1143. DOI: 10.1093/jnci/djn243.
    [32]
    SIEST G, SCHIELE F, GALTEAU MM, et al. Aspartate aminotransferase and alanine aminotransferase activities in plasma: statistical distributions, individual variations, and reference values[J]. Clin Chem, 1975, 21(8): 1077-1087. DOI: 10.1093/clinchem/21.8.1077
    [33]
    SHERMAN KE. Alanine aminotransferase in clinical practice. A review[J]. Arch Intern Med, 1991, 151(2): 260-265.
    [34]
    PRATT DS, KAPLAN MM. Evaluation of abnormal liver-enzyme results in asymptomatic patients[J]. N Engl J Med, 2000, 342(17): 1266-1271. DOI: 10.1056/NEJM200004273421707.
    [35]
    DEGERTEKIN B, TOZUN N, DEMIR F, et al. Determination of the upper limits of normal serum alanine aminotransferase (ALT) level in healthy Turkish population[J]. Hepatol Forum, 2020, 1(2): 44-47. DOI: 10.14744/hf.2020.2020.0012.
    [36]
    KAPLAN MM. Alanine aminotransferase levels: what's normal?[J]. Ann Intern Med, 2002, 137(1): 49-51. DOI: 10.7326/0003-4819-137-1-200207020-00012.
    [37]
    SENIOR JR. Healthy ranges for alanine aminotransferase levels[J]. Ann Intern Med, 2003, 138(2): 156-157; author reply 156-157. DOI: 10.7326/0003-4819-138-2-200301210-00020.
    [38]
    ZHUANG H. Should the threshold of alanine aminotransferase level for initiation of treatment for chronic hepatitis B be modified?[J]. Chin J Hepatol, 2021, 29(9): 878-881. DOI: 10.3760/cma.j.cn501113-20210823-00419.

    庄辉. 慢性乙型肝炎启动治疗的ALT阈值应否修订[J]. 中华肝脏病杂志, 2021, 29(9): 878-881. DOI: 10.3760/cma.j.cn501113-20210823-00419.
    [39]
    PRATI D, TAIOLI E, ZANELLA A, et al. Updated definitions of healthy ranges for serum alanine aminotransferase levels[J]. Ann Intern Med, 2002, 137(1): 1-10. DOI: 10.7326/0003-4819-137-1-200207020-00006.
    [40]
    LEE JK, SHIM JH, LEE HC, et al. Estimation of the healthy upper limits for serum alanine aminotransferase in Asian populations with normal liver histology[J]. Hepatology, 2010, 51(5): 1577-1583. DOI: 10.1002/hep.23505.
    [41]
    GAO ZL. Exploring the ALT threshold from the ALT level of patients with chronic hepatitis B for clinical cure in China (Mount Everest Engineering Project)[J]. Chin J Hepatol, 2021, 29(10): 1020-1021. DOI: 10.3760/cma.j.cn501113-20210823-00422.

    高志良. 从中国慢性乙型肝炎临床治愈(珠峰)工程项目患者ALT水平探讨启动治疗的ALT阈值[J]. 中华肝脏病杂志, 2021, 29(10): 1020-1021. DOI: 10.3760/cma.j.cn501113-20210823-00422.
    [42]
    LI SY, HU P. Antiviral therapy initiation with lower ALT threshold level benefits to achieve better long-term clinical outcomes in patients with chronic hepatitis B virus infection[J]. Chin J Hepatol, 2021, 29(10): 1017-1019. DOI: 10.3760/cma.j.cn501113-20210824-00426.

    李世颖, 胡鹏. 较低ALT阈值水平启动慢性乙型肝炎病毒感染者抗病毒治疗有益于获得更好的远期临床结局[J]. 中华肝脏病杂志, 2021, 29(10): 1017-1019. DOI: 10.3760/cma.j.cn501113-20210824-00426.
    [43]
    LIM YS, AHN SH, SHIM JJ, et al. Impact of expanding hepatitis B treatment guidelines: A modelling and economic impact analysis[J]. Aliment Pharmacol Ther, 2022, 56(3): 519-528. DOI: 10.1111/apt.17052.
    [44]
    ZHANG S, WANG C, LIU B, et al. Cost-effectiveness of expanded antiviral treatment for chronic hepatitis B virus infection in China: an economic evaluation[J]. Lancet Reg Health West Pac, 2023, 35: 100738. DOI: 10.1016/j.lanwpc.2023.100738.
    [45]
    WANG H, SHAN S, YOU H, et al. Effect of the change in antiviral therapy indication in increasing the treatment rate of chronic hepatitis B[J]. J Clin Hepatol, 2022, 38(6): 1269-1274. DOI: 10.3969/j.issn.1001-5256.2022.06.011.

    王皓, 单姗, 尤红, 等. 抗病毒治疗适应证变化对提高慢性乙型肝炎治疗率的影响[J]. 临床肝胆病杂志, 2022, 38(6): 1269-1274. DOI: 10.3969/j.issn.1001-5256.2022.06.011.
    [46]
    Country dashboard: China (2019), polaris observatory. CDA foundation[EB/OL]. https://cdafound.org/dashboard/polaris/dashboard.html.
    • 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

    Tables(4)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (673) PDF downloads(194) 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