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HBV cccDNA、HBsAg、HBV pgRNA联合检测对恩替卡韦治疗HBeAg阳性慢性乙型肝炎效果的预测价值
DOI: 10.3969/j.issn.1001-5256.2020.05.012
Value of combined measurement of hepatitis B virus covalently closed circular DNA,HBsAg,and hepatitis B virus pregenomic RNA in predicting the treatment outcome of HBeAg-positive chronic hepatitis B patients treated with entecavir
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摘要:
目的研究血清HBV共价闭合环状DNA（HBV cccDNA）、HBsAg、HBV前基因组RNA（HBV pgRNA）联合检测对恩替卡韦（ETV）治疗HBeAg阳性慢性乙型肝炎（CHB）患者的效果预测价值。方法将2015年5月-2017年5月经苏州大学附属第二医院确诊为HBeAg阳性的87例CHB患者纳入研究。根据患者ETV治疗48周后是否获得完全应答,分为获得组（n=38）和未获得组（n=49）。均采取ETV治疗,疗程48周,观测患者基线及治疗12、24、48周时血清HBV cccDNA、HBsAg、HBV pgRNA的水平。正态分布的计量资料组间比较采用t检验,非正态分布的采用Mann-WhitneyU检验。计数资料组间比较采用χ2检验;等级资料组间比较采用Mann-WhitneyU检验。采用Pearson相关分析探讨肝组织HBV cccDNA与血清HBsAg、HBV pgRNA的相关性。采用多因素logistic回归分析完全应答的预测因素,并采用受试者工作特征曲线（ROC曲线）评价血清HBV cccDNA、HBsAg、HBV pgRNA单独或联合检测对完全应答...
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关键词:
- 乙型肝炎,慢性 /
- DNA,环状 /
- HBV前基因组RNA /
- 恩替卡韦
Abstract:Objective To investigate value of combined measurement of serum hepatitis B virus(HBV) covalently closed circular DNA(cccDNA), HBsAg, and HBV pregenomic RNA(pgRNA) in predicting the treatment outcome of HBeAg-positive chronic hepatitis B(CHB) patients treated with entecavir(ETV).Methods A total of 87 HBeAg-positive CHB patients who were diagnosed and treated inThe Second Affiliated Hospital of Suzhou University from May 2015 to May 2017 were enrolled. All patients were treated with ETV for 48 weeks, and the serum levels of HBV cccDNA, HBsAg, and HBV pgRNA were measured at baseline and at weeks 12, 24, and 48 of treat-ment. Thet-test was used for comparison of normally distributed continuous data between groups, and the Mann-WhitneyUtest was usedfor comparison of non-normally distributed continuous data between groups. The chi-square test was used for comparison of categorical da-ta between groups, and the Mann-WhitneyUtest was used for comparison of ranked data between groups. A Pearson correlation analysiswas performed to determine the correlation of liver HBV cccDNA with serum HBsAg and HBV pgRNA. A multivariate logistic regression analysis was used to investigate the predictive factors for complete response, and the receiver operating characteristic(ROC) curve was usedto evaluate the value of serum HBV cccDNA, HBsAg, and HBV pgRNA measured alone or in combination in predicting complete response.Results Of all 87 HBeAg-positive CHB patients after 48 weeks of ETV treatment, 38 achieved complete response and 49 did not achievecomplete response. Compared with the non-complete response group, the complete response group had significant reductions in the levels ofHBV cccDNA at baseline and at weeks 24 and 48 of treatment(Z =-2. 452,-2. 518, and-2. 266, allP< 0. 001), HBsAg at baselineand at weeks 12, 24, and 48 of treatment(Z=-2. 431,-2. 750,-2. 386, and-2. 536, allP< 0. 001), and HBV pgRNA at weeks12, 24, and 48 of treatment(Z=-2. 674,-2. 503, and-2. 528, allP< 0. 001). Compared with the non-complete response group,the complete response group had significantly greater reductions in HBV cccDNA at week 24 of treatment, HBsAg at week 12 of treatment,and HBV pgRNA at week 12 of treatment(Z=-2. 352,-2. 566, and-2. 389,P= 0. 006, 0. 001, and 0. 004). Serum HBsAg andHBV pgRNA were positively correlated with HBV cccDNA in liver tissue(r= 0. 553 and 0. 757, bothP< 0. 001). The levels of HBVcccDNA at week 24 of treatment(odds ratio [OR] = 6. 248, 95% confidence interval [CI]: 1. 574-14. 262,P< 0. 05), HBsAg at week12 of treatment(OR = 5. 452, 95% CI: 2. 048-16. 888,P< 0. 05), and HBV pgRNA at week 12 of treatment(OR = 5. 670, 95% CI:1. 201-16. 183,P< 0. 05) were predictive factors for complete response. As for the area under the ROC curve(AUC), HBV cccDNA,HBsAg, or HBV pgRNA measured alone had a significantly lower AUC than the combined measurement of the three indices(0. 845/0. 741/0. 773 vs 0. 913, allP< 0. 001), and the patients with a value of < 9. 7 could achieve complete response at week 48 of treatment.Conclusion Combined measurement of serum HBV cccDNA, HBsAg, and HBV pgRNA has a good value in predicting the treatment outcome ofHBeAg-positive CHB patients treated with ETV.
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Key words:
- hepatitis B,chronic /
- DNA,circular /
- HBV pgRNA /
- entecavir
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[1] PAN HY, PAN HY, SONG WY, et al. Long-term outcome of telbivudine versus entecavir in treating higher viral load chronic hepatitis B patients without cirrhosis[J]. J Viral Hepat, 2017,24(Suppl 1):29-35. [2] PAPATHEODORIDIS GV, SYPSA V, DALEKOS G, et al. Eightyear survival in chronic hepatitis B patients under long-term entecavir or tenofovir therapy is similar to the general population[J].J Hepatol, 2018, 68(6):1129-1136. [3] Chinese Society of Infectious Disease, Chinese Society of Hepatology, Chinese Medical Association. The expert consensus on functional cure of chronic hepatitis B[J]. J Clin Hepatol, 2019, 35(8):1693-1701.(in Chinese）中华医学会感染病学分会，中华医学会肝病学分会．慢性乙型肝炎临床治愈（功能性治愈）专家共识[J]．临床肝胆病杂志，2019, 35(8):1693-1701. [4] Chinese Society of Hepatology and Chinese Society of Infectious Disease,Chinese Medical Association. Guidelines for the Prevention and treatment of chronic Hepatitis B(updated V2015)[J]. J Clin Hepatol, 2015, 31(12):1941-1960.(in Chinese）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. [5] YAO GB, REN H, XU DZ, et al. Continuous treatment of entecavir in patients with chronic hepatitis B for 3 years[J]. Chin J Hepatol, 2009,17(12):884-886.(in Chinese）姚光弼，任红，徐道振，等．慢性乙型肝炎患者持续应用恩替卡韦的疗效[J]．中华肝脏病杂志，2009, 17(12):884-886. [6] VLACHOGIANNAKOS J, PAPATHEODORIDIS GV. Optimal therapy of chronic hepatitis B:How do I treat HBeAg-positive patients?[J]. Liver Int, 2015, 35(Suppl 1):100-106. [7] GUO Y, LI Y, MU S, et al. Evidence that methylation of hepatitis B virus covalently closed circular DNA in liver tissues of patients with chronic hepatitis B modulates HBV replication[J]. J Med Virol, 2009, 81(7):1177-1183. [8] SPANGENBERG HC, THIMME R, BLUM HE. Tracking cccDNA in chronic HBV infection[J]. Hepatology, 2004, 39(6):1736-1738. [9] CHONG CL, CHEN ML, WU YC, et al. Dynamics of HBV cccDNA expression and transcription in different cell growth phase[J]. J Biomed Sci, 2011, 18:96. [10] WU M, LI J, YUE L, et al. Establishment of Cre-mediated HBV recombinant cccDNA(rcccDNA)cell line for cccDNA biology and antiviral screening assays[J]. Antiviral Res, 2018,152:45-52. [11] BUTLER EK, GERSCH J, MCNAMARA A, et al. Hepatitis B virus serum DNA andRNA levels in nucleos(t)ide analog-treated or untreated patients during chronic and acute infection[J]. Hepatology, 2018, 68(6):2106-2117. [12] GAO N, WU RH, WANG XM, et al. Predictive value of HBsAg quantitative test for prognosis of patients with chronic severe hepatitis B[J]. J Clin Hepatol, 2016, 32(4):192-194.(in Chinese）高娜，吴瑞红，王晓美，等．HBsAg定量检测对慢性重型乙型肝炎患者预后的预测价值[J]．临床肝胆病杂志，2016, 32(4):192-194. [13] ZHOU YQ, LI C. Value of HBsAg quantification in individualized anti-HBV treatment with nucleos(t)ide analogues[J]. J Clin Hepatol, 2019, 35(8):1821-1823.(in Chinese）周友乾，李翠．HBsAg定量在核苷（酸）类似物个体化抗HBV治疗中的应用价值[J]．临床肝胆病杂志，2019, 35(8):1821-1823. [14] PENG H, WEI F, LIU JY, et al. Response-guided therapy of regimens based on PEG-interferon for chronic hepatitis B using on-treatment hepatitis B surface antigen quantification:A meta-analysis[J]. Hepatol Int, 2015, 9(4):543-557. [15] van BOMMMEL F, BERG T. Stopping long-term treatment with nucleos(t)ide analogues is a favourable option for selected patients with HBeAg-negative chronic hepatitis B[J]. Liver Int, 2018, 38(Suppl 1):90-96. [16] TAN N, LUO H, XU XY. Significance of hepatitis B virus pregenomic RNA in the progression of chronic hepatitis B[J]. J Clin Hepatol, 2018, 34(10):2221-2223.(in Chinese）谭宁，罗皓，徐小元．HBV pgRNA在慢性乙型肝炎进程中的可能意义[J]．临床肝胆病杂志，2018, 34(10):2221-2223. [17] ZHANG S, SUN J, XING HC. Progress on new anti-hepatitis B viral drugs[J/CD]. Chin J Exp Clin Infect Dis(Electronic Edition), 2019, 13(1):6-11.(in Chinese）张珊，孙静，邢卉春．新型抗乙型肝炎病毒药物研究进展[J/CD]．中华实验和临床感染病杂志（电子版），2019, 13(1):6-11. [18] CAREY I, GERSCH J, WANG B, et al. Pre-genomic HBV RNA and HBcrAg predict outcomes in HBeAg negative chronic hepatitis B patients suppressed on nucleos(t)ide analogue therapy[J]. Hepatology, 2019.[Online ahead of print]. [19] YIN XR, FAN R, HOU JL. A 10-year prospective, random, observational study involving 24 countries in the world for long-term treatment of chronic hepatitis B with entecavir or other oral antiviral drugs[J]. J Clin Hepatol, 2019, 35(9):2005.(in Chinese）尹雪如，樊蓉，侯金林．一项为期10年、涉及全球24国的恩替卡韦或其他口服抗病毒药物长期治疗慢性乙型肝炎的前瞻性、随机、观察性研究结果[J]．临床肝胆病杂志，2019, 35(9):2005. 期刊类型引用(5)
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