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Volume 37 Issue 10
Oct.  2021
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Article Contents

Expert consensus on diagnosis and treatment of chronic hepatitis B virus with persistently normal alanine aminotransferase

DOI: 10.3969/j.issn.1001-5256.2021.10.007
Research funding:

National Science and Technology Key Project on “Major Infectious Diseases such as HIV/AIDS, Viral Hepatitis Preventon and Treatment” (2013ZX10005002);

National Science and Technology Key Project on “Major Infectious Diseases such as HIV/AIDS, Viral Hepatitis Preventon and Treatment” (2017ZX1020101201-006);

National Science and Technology Key Project on “Major Infectious Diseases such as HIV/AIDS, Viral Hepatitis Preventon and Treatment” (2018ZX10725506)

  • Received Date: 2021-08-26
  • Accepted Date: 2021-08-26
  • Published Date: 2021-10-20
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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. 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]
    CHENG JL, WANG XL, YANG SG, et al. Non-ALT biomarkers for markedly abnormal liver histology among Chinese persistently normal alanine aminotransferase-chronic hepatitis B patients[J]. World J Gastroenterol, 2017, 23(15): 2802-2810. DOI: 10.3748/wjg.v23.i15.2802.
    [3]
    CHAO DT, LIM JK, AYOUB WS, et al. Systematic review with meta-analysis: The proportion of chronic hepatitis B patients with normal alanine transaminase ≤ 40 IU/L and significant hepatic fibrosis[J]. Aliment Pharmacol Ther, 2014, 39(4): 349-358. DOI: 10.1111/apt.12590.
    [4]
    CHANG XJ, WANG J, CHEN Y, et al. A novel nomogram to predict evident histological liver injury in patients with HBeAg-positive chronic hepatitis B virus infection[J]. EBioMedicine, 2021, 67: 103389. DOI: 10.1016/j.ebiom.2021.103389.
    [5]
    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.
    [6]
    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.
    [7]
    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.
    [8]
    HARBOUR R, MILLER J. A new system for grading recommendations in evidence based guidelines[J]. BMJ, 2001, 323(7308): 334-336. DOI: 10.1136/bmj.323.7308.334.
    [9]
    SHANG H, CHEN WX, PAN BS, et al. Reference intervals for common tests of liver function, electrolytes and blood cell analysis of Chinese adults[J]. Chin J Lab Med, 2013, 36(5): 393-394. DOI: 10.3760/cma.j.issn.1009-9158.2013.05.003.

    尚红, 陈文祥, 潘柏申, 等. 中国成人常用肝功能和电解质及血细胞分析项目参考区间[J]. 中华检验医学杂志, 2013, 36(5): 393-394. DOI: 10.3760/cma.j.issn.1009-9158.2013.05.003.
    [10]
    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.
    [11]
    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.
    [12]
    CHEN EQ, HUANG FJ, HE LL, et al. Histological changes in chinese chronic hepatitis B patients with ALT lower than two times upper limits of normal[J]. Dig Dis Sci, 2010, 55(2): 432-437. DOI: 10.1007/s10620-009-0724-5.
    [13]
    CHANG Y, RYU S, SUNG E, et al. Higher concentrations of alanine aminotransferase within the reference interval predict nonalcoholic fatty liver disease[J]. Clin Chem, 2007, 53(4): 686-692. DOI: 10.1373/clinchem.2006.081257.
    [14]
    KIM BK, HAN KH, AHN SH. "Normal" range of alanine aminotransferase levels for Asian population[J]. J Gastroenterol Hepatol, 2011, 26(2): 219-220. DOI: 10.1111/j.1440-1746.2010.06603.x.
    [15]
    TERRAULT NA, BZOWEJ NH, CHANG KM, et al. AASLD guidelines for treatment of chronic hepatitis B[J]. Hepatology, 2016, 63(1): 261-283. DOI: 10.1002/hep.28156.
    [16]
    SOHN W, JUN DW, KWAK MJ, et al. Upper limit of normal serum alanine and aspartate aminotransferase levels in Korea[J]. J Gastroenterol Hepatol, 2013, 28(3): 522-529. DOI: 10.1111/j.1440-1746.2012.07143.x.
    [17]
    TANAKA K, HYOGO H, ONO M, et al. Upper limit of normal serum alanine aminotransferase levels in Japanese subjects[J]. Hepatol Res, 2014, 44(12): 1196-1207. DOI: 10.1111/hepr.12293.
    [18]
    ZHENG MH, SHI KQ, FAN YC, et al. Upper limits of normal for serum alanine aminotransferase levels in Chinese Han population[J]. PLoS One, 2012, 7(9): e43736. DOI: 10.1371/journal.pone.0043736.
    [19]
    TSENG TC, LIU CJ, HSU CY, et al. High level of hepatitis B core-related antigen associated with increased risk of hepatocellular carcinoma in patients with chronic HBV infection of intermediate viral load[J]. Gastroenterology, 2019, 157(6): 1518-1529. e3. DOI: 10.1053/j.gastro.2019.08.028.
    [20]
    MARTINOT-PEIGNOUX M, BOYER N, COLOMBAT M, et al. Serum hepatitis B virus DNA levels and liver histology in inactive HBsAg carriers[J]. J Hepatol, 2002, 36(4): 543-546. DOI: 10.1016/s0168-8278(02)00004-1.
    [21]
    IKEDA K, ARASE Y, SAITOH S, et al. Long-term outcome of HBV carriers with negative HBe antigen and normal aminotransferase[J]. Am J Med, 2006, 119(11): 977-985. DOI: 10.1016/j.amjmed.2006.04.036.
    [22]
    TAN YW, ZHOU XB, YE Y, et al. Diagnostic value of FIB-4, aspartate aminotransferase-to-platelet ratio index and liver stiffness measurement in hepatitis B virus-infected patients with persistently normal alanine aminotransferase[J]. World J Gastroenterol, 2017, 23(31): 5746-5754. DOI: 10.3748/wjg.v23.i31.5746.
    [23]
    WANG D, ZHANG P, ZHANG M. Predictors for advanced liver fibrosis in chronic hepatitis B virus infection with persistently normal or mildly elevated alanine aminotransferase[J]. ExpTher Med, 2017, 14(6): 5363-5370. DOI: 10.3892/etm.2017.5219.
    [24]
    CHEN CJ, YANG HI. Natural history of chronic hepatitis B REVEALed[J]. J Gastroenterol Hepatol, 2011, 26(4): 628-638. DOI: 10.1111/j.1440-1746.2011.06695.x.
    [25]
    SHIM JJ, KIM JW, OH CH, et al. Serum alanine aminotransferase level and liver-related mortality in patients with chronic hepatitis B: A large national cohort study[J]. Liver Int, 2018, 38(10): 1751-1759. DOI: 10.1111/liv.13705.
    [26]
    CHOI GH, KIM GA, CHOI J, et al. High risk of clinical events in untreated HBeAg-negative chronic hepatitis B patients with high viral load and no significant ALT elevation[J]. Aliment Pharmacol Ther, 2019, 50(2): 215-226. DOI: 10.1111/apt.15311.
    [27]
    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.
    [28]
    ORMECI A, AYDIN Y, SUMNU A, et al. Predictors of treatment requirement in HBeAg-negative chronic hepatitis B patients with persistently normal alanine aminotransferase and high serum HBV DNA levels[J]. Int J Infect Dis, 2016, 52: 68-73. DOI: 10.1016/j.ijid.2016.09.007.
    [29]
    WANG H, XUE L, YAN R, et al. Comparison of histologic characteristics of Chinese chronic hepatitis B patients with persistently normal or mildly elevated ALT[J]. PLoS One, 2013, 8(11): e80585. DOI: 10.1371/journal.pone.0080585.
    [30]
    ALAM MM, MAHTAB MA, AKBAR SM, et al. Hepatic necroinflammation and severe liver fibrosis in patients with chronic hepatitis B with undetectable HBV DNA and persistently normal alanine aminotransferase[J]. Bangladesh Med Res Counc Bull, 2014, 40(3): 92-96. DOI: 10.3329/bmrcb.v40i3.25229.
    [31]
    OU WN, ZHANG N, WANG XM, et al. The related factors of antiviral response in ALT normal or mild elevated patients with chronic hepatitis B[J/CD]. Chin J Exp Clin Infect Dis(Electronic Edition), 2016, 10(4): 417-421. DOI: 10.3877/cma.j.issn.1674-1358.2016.04.007.

    欧蔚妮, 张娜, 王笑梅, 等. 丙氨酸氨基转移酶正常或轻度升高的慢性乙型肝炎患者抗病毒疗效的影响因素[J/CD]. 中华实验和临床感染病杂志(电子版), 2016, 10(4): 417-421. DOI: 10.3877/cma.j.issn.1674-1358.2016.04.007.
    [32]
    XIANG TX, TAO XP, LI XN, et al. Study on interferon gamma spot level of chronic hepatitis B infection in different immune stages and optimal opportunity of antiviral treatment in low levels of ALT patients[J]. Int J Virol, 2015, 22(3): 157-161. DOI: 10.3760/cma.j.issn.1673-4092.2015.03.004.

    向天新, 陶学萍, 李细女, 等. 慢性乙肝病毒感染者不同免疫阶段IFN-γ斑点水平及其在低丙氨酸氨基转移酶抗病毒治疗中的作用[J]. 国际病毒学杂志, 2015, 22(3): 157-161. DOI: 10.3760/cma.j.issn.1673-4092.2015.03.004.
    [33]
    TAN Y, YE Y, ZHOU X, et al. Age as a predictor of significant fibrosis features in HBeAg-negative chronic hepatitis B virus infection with persistently normal alanine aminotransferase[J]. PLoS One, 2015, 10(4): e0123452. DOI: 10.1371/journal.pone.0123452.
    [34]
    KIM WR, BERG T, ASSELAH T, et al. Evaluation of APRI and FIB-4 scoring systems for non-invasive assessment of hepatic fibrosis in chronic hepatitis B patients[J]. J Hepatol, 2016, 64(4): 773-780. DOI: 10.1016/j.jhep.2015.11.012.
    [35]
    SONNEVELD MJ, BROUWER WP, CHAN HL, et al. Optimisation of the use of APRI and FIB-4 to rule out cirrhosis in patients with chronic hepatitis B: Results from the SONIC-B study[J]. Lancet Gastroenterol Hepatol, 2019, 4(7): 538-544. DOI: 10.1016/S2468-1253(19)30087-1.
    [36]
    DING W, QIU Q, LIU G, et al. Metadata checklist: Identification of CHI3L1 and MASP2 as a biomarker pair for liver cancer through integrative secretome and transcriptome analysis[J]. OMICS, 2014, 18(10): 658-661. DOI: 10.1089/omi.2014.0090.
    [37]
    WANG L, LIU T, ZHOU J, et al. Changes in serum chitinase 3-like 1 levels correlate with changes in liver fibrosis measured by two established quantitative methods in chronic hepatitis B patients following antiviral therapy[J]. Hepatol Res, 2018, 48(3): e283-e290. DOI: 10.1111/hepr.12982.
    [38]
    LIU KH, LI FL, WANG H. Value of cytokeratin 18 in the diagnosis of chronic liver disease[J]. Chin Hepatol, 2013, 18(10): 710-714. DOI: 10.3969/j.issn.1008-1704.2013.10.018.

    刘柯慧, 李凤棣, 王晖. 细胞角蛋白18在慢性肝病诊断中的价值[J]. 肝脏, 2013, 18(10): 710-714. DOI: 10.3969/j.issn.1008-1704.2013.10.018.
    [39]
    JIA J, HOU J, DING H, et al. Transient elastography compared to serum markers to predict liver fibrosis in a cohort of Chinese patients with chronic hepatitis B[J]. J Gastroenterol Hepatol, 2015, 30(4): 756-762. DOI: 10.1111/jgh.12840.
    [40]
    SINGH S, VENKATESH SK, WANG Z, et al. Diagnostic performance of magnetic resonance elastography in staging liver fibrosis: A systematic review and meta-analysis of individual participant data[J]. Clin Gastroenterol Hepatol, 2015, 13(3): 440-451. e6. DOI: 10.1016/j.cgh.2014.09.046.
    [41]
    Chinese Portal Hypertension Diagnosis and Monitoring Study Group (CHESS); Minimally Invasive Intervention Collaborative Group, Chinese Society of Gastroenterology; Emergency Intervention Committee, Chinese College of Interventionalists, et al. Consensus on clinical application of hepatic venous pressure gradient in China (2018)[J]. J Clin Hepatol, 2018, 34(12): 2526-2536. DOI: 10.3969/j.issn.1001-5256.2018.12.008.

    中国门静脉高压诊断与监测研究组(CHESS), 中华医学会消化病学分会微创介入协作组, 中国医师协会介入医师分会急诊介入专业委员会, 等. 中国肝静脉压力梯度临床应用专家共识(2018版)[J]. 临床肝胆病杂志, 2018, 34(12): 2526-2536. DOI: 10.3969/j.issn.1001-5256.2018.12.008.
    [42]
    ZHANG WH, ZHANG DZ, DOU XG, et al. Consensus on pegylated interferon alpha in treatment of chronic hepatitis B[J]. Chin J Hepatol, 2017, 25(9): 678-686. DOI: 10.3760/cma.j.issn.1007-3418.2017.09.007.

    张文宏, 张大志, 窦晓光, 等. 聚乙二醇干扰素α治疗慢性乙型肝炎专家共识[J]. 中华肝脏病杂志, 2017, 25(9): 678-686. DOI: 10.3760/cma.j.issn.1007-3418.2017.09.007.
    [43]
    ZHU P. How to treat antiviral treatment in patients with chronic hepatitis B[J]. Ganboshi, 2019, (3): 31-32. https://www.cnki.com.cn/Article/CJFDTOTAL-GBSH201903017.htm

    朱萍. 慢乙肝患者该如何抗病毒治疗[J]. 肝博士, 2019, (3): 31-32. https://www.cnki.com.cn/Article/CJFDTOTAL-GBSH201903017.htm
    [44]
    LI JL. Antiviral treatment of hepatitis B related primary liver cancer[J]. J Mod Med Health, 2019, 35(22): 3409-3410, 3413. DOI: 10.3969/j.issn.1009-5519.2019.22.001.

    李俊利. 乙型肝炎相关原发性肝癌的抗病毒药物治疗选择[J]. 现代医药卫生, 2019, 35(22): 3409-3410, 3413. DOI: 10.3969/j.issn.1009-5519.2019.22.001.
    [45]
    REN TQ, YANG QQ, MA HM, et al. Research progress of TAF in the treatment of chronic hepatitis B[J]. Chin Hepatol, 2019, 24(11): 1319-1322. DOI: 10.3969/j.issn.1008-1704.2019.11.037.

    任天棋, 杨倩倩, 马鹤铭, 等. TAF治疗慢性乙型肝炎的研究进展[J]. 肝脏, 2019, 24(11): 1319-1322. DOI: 10.3969/j.issn.1008-1704.2019.11.037.
    [46]
    DIAO QF, HUANG B. Comparison of adefovir and lamivudine against hepatitis B virus[J]. Chin J Clin Ration Drug Use, 2020, 13(14): 73-74. DOI: 10.15887/j.cnki.13-1389/r.2020.14.042.

    刁勤峰, 黄斌. 阿德福韦酯与拉米夫定抗乙型肝炎病毒效果比较[J]. 临床合理用药杂志, 2020, 13(14): 73-74. DOI: 10.15887/j.cnki.13-1389/r.2020.14.042.
    [47]
    CHEN CH, HSU YC, LU SN, et al. The incidence and predictors of HBV relapse after cessation of tenofovir therapy in chronic hepatitis B patients[J]. J Viral Hepat, 2018, 25(5): 590-597. DOI: 10.1111/jvh.12851.
    [48]
    YAO CC, HUNG CH, HU TH, et al. Incidence and predictors of HBV relapse after cessation of nucleoside analogues in HBeAg-negative patients with HBsAg≤200 IU/mL[J]. Sci Rep, 2017, 7(1): 1839. DOI: 10.1038/s41598-017-02010-w.
    [49]
    XIONG WJ. Meta analysis of Chinese patent medicine in the national medical insurance drug catalogue in the treatment of chronic hepatitis B[D]. Beijing: Beijing University of Chinese Medicine, 2016.

    熊文婧. 国家医保药物目录中成药治疗慢性乙型肝炎的网状Meta分析[D]. 北京: 北京中医药大学, 2016.
    [50]
    CHEN YY, WANG Z, NAN JY, et al. Development of TCM treatment for Chronic Hepatitis B[J]. World J Integr Tradit Western Med, 2020, 15(4): 779-784. DOI: 10.3969/j.issn.1673-7202.2011.01.049.

    陈寅萤, 王忠, 南景一, 等. 中医药治疗慢性乙型肝炎的研究进展[J]. 世界中西医结合杂志, 2020, 15(4): 779-784. DOI: 10.3969/j.issn.1673-7202.2011.01.049.
    [51]
    Hepatobiliary Specialized Committee of China Association of Chinese Medicine, Liver Diseases Specialized Committee of China Medical Association of Minorities. The clinical guidelines of diagnosis and treatment of chronic hepatitis B with traditional Chinese medicine(2018)[J]. J Clin Hepatol, 2018, 34(12): 2520-2525. DOI: 10.3969/j.issn.1001-5256.2018.12.007.

    中华中医药学会肝胆病专业委员会, 中国民族医药学会肝病专业委员会. 慢性乙型肝炎中医诊疗指南(2018年版)[J]. 临床肝胆病杂志, 2018, 34(12): 2520-2525. DOI: 10.3969/j.issn.1001-5256.2018.12.007.
    [52]
    WANG L, TAN DM, GONG GZ, et al. A randomized, double-blind, positive control, multicenter clinical study of lefuneng in the treatment of chronic hepatitis B for 12 weeks[C]. The 13th National Conference on infectious diseases of Chinese Medical Association, 2014.

    汪玲, 谭德明, 龚国忠, 等. 乐复能治疗慢性乙型肝炎12周随机、双盲、阳性对照、多中心临床研究分析[C]. 中华医学会第十三次全国感染病学术会议论文汇编, 2014.
    [53]
    LIANG L, BI Q, DONG JC, et al. Progress on the development of natural medicines with hepatoprotective effects[J]. Biotic Resources, 2018, 40(2): 148-158. DOI: 10.14188/j.ajsh.2018.02.009.

    梁丽, 毕倩, 董金材, 等. 具有保肝作用的天然药物开发进展[J]. 生物资源, 2018, 40(2): 148-158. DOI: 10.14188/j.ajsh.2018.02.009.
    [54]
    XIA Y, GUO H. Hepatitis B virus cccDNA: Formation, regulation and therapeutic potential[J]. Antiviral Res, 2020, 180: 104824. DOI: 10.1016/j.antiviral.2020.104824.
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