Noninvasive indicators of indications for antiviral therapy in HBeAg-negative chronic HBV infection patients with alanine aminotransferase ≤40 U/L

Chunxia LI; Bing DONG; Lulu ZHOU; Dandan REN; Ruiqin ZHANG; He GUO; Guanghua XU; Na LIU

doi:10.3969/j.issn.1001-5256.2021.01.011

Volume 37 Issue 1

Jan. 2021

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Article Navigation > Journal of Clinical Hepatology > 2021 > 37(1): 51-55

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Noninvasive indicators of indications for antiviral therapy in HBeAg-negative chronic HBV infection patients with alanine aminotransferase ≤40 U/L

DOI: 10.3969/j.issn.1001-5256.2021.01.011

Department of Infectious Diseases, Affiliated Hospital of Yan'an University, Yan'an, Shaanxi 716000, China

Received Date: 2020-07-06
Accepted Date: 2020-09-07
Published Date: 2021-01-20

Abstract

Abstract

Objective To investigate the noninvasive indicators of indications for antiviral therapy in HBeAg-negative chronic hepatitis B virus (HBV) infection patients with alanine aminotransferase (ALT) ≤40 U/L under the guidance of liver pathology. Methods A retrospective analysis was performed for the clinical data of 377 HBeAg-negative chronic HBV infection patients with ALT ≤40 U/L who were hospitalized in Affiliated Hospital of Yan'an University, from October 2013 to August 2018 and underwent liver biopsy, among whom the patients with inflammatory activity < A2 and fibrosis stage < F2 were enrolled as non-antiviral therapy group(n=266), and the patients with inflammatory activity ≥A2 or fibrosis stage ≥F2 were enrolled as antiviral therapy group(n=111). The chi-square test was used for comparison of categorical data between two groups; the t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; univariate and multivariate binary logistic regression analyses were used to screen out the influencing factors for the initiation of antiviral therapy; the receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic efficiency of each indicator in determining the need for antiviral therapy in HBeAg-negative chronic HBV infection patients with ALT ≤40 U/L. Results Of all 377 patients, 266 (70.6%) did not need antiviral therapy for the time being, and 111 (29.4%) had marked liver damage and thus needed active antiviral therapy. The multivariate analysis showed that liver stiffness measurement (LSM) (odds ratio [HR]=2.003, 95% confidence interval [CI]: 1.647-2.437, P < 0.05), HBsAg (HR=1.563, 95% CI: 1.110-2.200, P < 0.05), HBV DNA (HR=1.519, 95% CI: 1.173-1.966, P < 0.05), and albumin (HR=0.939, 95% CI: 0.884-0.998, P < 0.05) were independent influencing factors for the initiation of antiviral therapy. The ROC curve analysis showed that the area under the ROC curve (AUC) was 0.749 (95% CI: 0.699-0.799) for LSM, 0.642 (95% CI: 0.586-0.699) for HBV DNA, and 0.565 (95% CI: 0.507-0.623) for HBsAg, and the combination of LSM, HBV DNA, and HBsAg had a larger AUC of 0.779 (95% CI: 0.732-0.827). Conclusion The levels of LSM, HBV DNA, and HBsAg have a reference value in determining the initiation of antiviral therapy in HBeAg-negative chronic HBV infection patients with ALT≤40 U/L.
- Hepatitis B Virus,
- Hepatitis B e Antigens,
- Alanine Transaminase,
- Antiviral Treatment

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[1]	LOZANO R, NAGHAVI M, FOREMAN K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: A systematic analysis for the Global Burden of Disease Study 2010[J]. Lancet, 2012, 380(9859): 2095-2128. DOI: 10.1016/S0140-6736(12)61728-0
[2]	Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Infectious Diseases, Chinese Medical Association. The guideline of prevention and treatment for chronic hepatitis B:A 2015 update[J]. J Clin Hepatol, 2015, 23(12): 1941-1960. (in Chinese) 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年更新版)[J]. 临床肝胆病杂志, 2015, 31(12): 1941-1960. DOI: 10.3969/j.issn.1001-5256.2015.12.002
[3]	PAPATHEODORIDIS G, VLACHOGIANNAKOS I, CHOLONGITAS E, et al. Discontinuation of oral antivirals in chronic hepatitis B: A systematic review[J]. Hepatology, 2016, 63(5): 1481-1492. DOI: 10.1002/hep.28438
[4]	TERRAULT NA, LOK ASF, MCMAHON BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance[J]. Hepatology (Baltimore, Md), 2018, 67(4): 1560-1599. DOI: 10.1002/hep.29800
[5]	BERSOFF-MATCHA SJ, CAO K, JASON M, et al. Hepatitis B virus reactivation associated with direct-acting antiviral therapy for chronic hepatitis C virus: A review of cases reported to the U.S. Food and Drug Administration Adverse Event Reporting System[J]. Ann Intern Med, 2017, 166(11): 792-798. DOI: 10.7326/M17-0377
[6]	ZHAO DF.Relationship between ALT, AST, HBeAg and serum HBV DNA content in chronic hepatitis B virus carriers[J/CD]. Chin J Clin Lab Sci(Electronic Edition), 2017, 6(1): 11-13. (in Chinese) 赵冬凤. 慢性乙肝病毒携带者ALT、AST及HBeAg与血清HBV DNA含量的关系[J/CD]. 临床检验杂志(电子版), 2017, 6(1): 11-13.
[7]	ZHOU LL, LIU N, LI CX, et al. Current status of the diagnosis and treatment of chronic hepatitis B virus infection with immune control[J]. J Clin Hepatol, 2020, 36(5): 1134-1137. (in Chinese). DOI: 10.3969/j.issn.1001-5256.2020.05.041 周路路, 刘娜, 李春霞, 等. 慢性HBV感染免疫控制期的抗病毒治疗[J]. 临床肝胆病杂志, 2020, 36(5): 1134-1137. DOI: 10.3969/j.issn.1001-5256.2020.05.041
[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. (in Chinese) 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]	LI Q, CHEN L, ZHOU Y. Diagnostic accuracy of liver stiffness measurement in chronic hepatitis B patients with normal or mildly elevated alanine transaminase levels[J]. Sci Rep, 2018, 8(1): 5224. DOI: 10.1038/s41598-018-23646-2
[10]	BRAVO AA, SHETH SG, CHOPRA S. Liver biopsy[J]. N Engl J Med, 2001, 344(7): 495-500. DOI: 10.1056/NEJM200102153440706
[11]	BEDOSSA P, POYNARD T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group[J]. Hepatology, 1996, 24(2): 289-293. DOI: 10.1002/hep.510240201
[12]	CASTERA L, FORNS X, ALBERTI A. Non-invasive evaluation of liver fibrosis using transient elastography[J]. J Hepatol, 2008, 48(5): 835-847. DOI: 10.1016/j.jhep.2008.02.008
[13]	ZHAO Y, LI YE, QI L, et al. Antiviral curative effects of tenofovir and entecavir in treatment of aged patients with chronic hepatitis B and their regulation on inflammation factors[J]. J Jilin Univ(Med Edit), 2019, 45(1): 117-122. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-BQEB201901022.htm 赵阳, 李烨, 齐玲, 等. 替诺福韦酯和恩替卡韦治疗老年慢性乙型肝炎患者的抗病毒疗效及对致炎细胞因子的调节作用[J]. 吉林大学学报(医学版), 2019, 45(1): 117-122. https://www.cnki.com.cn/Article/CJFDTOTAL-BQEB201901022.htm
[14]	LIM SG. Influencing factors of initiation and timing of discontinuation of treatment for chronic hepatitis B[J/CD]. Chin J Exp Clin Infect Dis (Electronic Edition), 2019, 13(6):528.(in Chinese) Seng-Gee LIM. 慢性乙型肝炎治疗开始和停药时机的影响因素[J/CD]. 中华实验和临床感染病杂志(电子版), 2019, 13(6): 528.
[15]	DOU XG.Anti-virus treatment strategies for chronic hepatitis B virus infection with normal alanine aminotransferase[J]. Chin J Pract Intern Med, 2013, 33(6): 454-456. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-SYNK201306014.htm 窦晓光. 丙氨酸转氨酶正常的慢性乙型肝炎病毒感染人群抗病毒治疗策略[J]. 中国实用内科杂志, 2013, 33(6): 454-456. https://www.cnki.com.cn/Article/CJFDTOTAL-SYNK201306014.htm
[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]	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
[18]	BAI XX, DONG B, GAO HY, et al. Clinical features of immune escape phase and immune control phase of chronic HBV infection[J]. J Clin Hepatol, 2018, 34(12): 2568-2571. (in Chinese) DOI: 10.3969/j.issn.1001－5256.2018.12.012 白萧萧, 东冰, 高红艳, 等. 慢性HBV感染者免疫逃逸期与免疫控制期的临床特征分析[J]. 临床肝胆病杂志, 2018, 34(12): 2568-2571. DOI: 10.3969/j.issn.1001－5256.2018.12.012
[19]	LIU WR, TIAN MX, JIN L, et al. High levels of hepatitis B surface antigen are associated with poorer survival and early recurrence of hepatocellular carcinoma in patients with low hepatitis B viral loads[J]. Ann Surg Oncol, 2015, 22(3): 843-850. DOI: 10.1245/s10434-014-4043-5
[20]	TSENG T C, LIU C J, YANG H C, 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. DOI: 10.1053/j.gastro.2012.02.007
[21]	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
[22]	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. http://www.ncbi.nlm.nih.gov/pubmed/21692932/

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Noninvasive indicators of indications for antiviral therapy in HBeAg-negative chronic HBV infection patients with alanine aminotransferase ≤40 U/L

DOI: 10.3969/j.issn.1001-5256.2021.01.011