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Expression level of serum HBV RNA in HBeAg-positive chronic hepatitis B patients at different periods and its value of measurement
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摘要:
目的 探讨血清HBV RNA在HBeAg阳性慢性乙型肝炎(CHB)患者不同时期的表达水平及潜在临床价值。 方法 选取2019年8月—2020年12月于杭州市西溪医院肝病科门诊及住院部就诊的CHB患者61例，根据HBeAg阳性CHB患者的抗病毒治疗情况分为3组：HBeAg阳性CHB[HBeAg(+)、HBV DNA(+)]未治患者(A组)，HBeAg血清学转换前[HBeAg(+)、HBV DNA(-)]经治患者(B组)，HBeAg血清学转换后[HBeAg(-)、HBV DNA(-)]经治患者(C组)，检测不同时期患者外周血HBV RNA载量，并分析其与HBsAg、HBV D NA的相关性。符合正态分布的计量资料2组间比较采用t检验；非正态分布的计量资料2组间比较采用Mann-Whitney U检验；计数资料2组间比较采用χ2检验；采用Pearson或Spearman相关分析描述两变量间的相关性。 结果 3组患者HBV RNA阳性率分别为100%(22/22)、88.2%(15/17)、22.7%(6/22)。HBeAg阳性CHB未治患者HBV RNA与HBsAg、HBV DNA均呈正相关(r值分别为0.612、0.922，P值均＜0.01)，在HBeAg血清学转换前和HBeAg血清学转换后的经治患者中，HBV RNA与HBsAg无相关性。经治HBeAg阳性组的HBV RNA、HBsAg均高于HBeAg阴性组，差异均有统计学意义(Z值分别为-4.44、-2.41，P值均＜0.05)。HBV DNA阳性组HBV RNA显著高于HBV DNA阴性组，差异有统计学意义(Z=-6.16, P＜0.01)。 结论 CHB患者经核苷(酸)类药物抗病毒治疗HBV DNA阴转后仍有部分患者能检测出血清HBV RNA；且HBV RNA只能来自肝内cccDNA, 因此HBV RNA比HBV DNA更能反映肝内病毒复制活性，对CHB人群管理有着一定的临床价值。 Abstract:Objective To investigate the expression level and potential clinical value of serum HBV RNA in HBeAg-positive chronic hepatitis B (CHB) patients at different periods. Methods A total of 61 CHB patients who attended the outpatient and inpatient services of Department of Hepatology, Hangzhou Xixi Hospital, from August 2019 to December 2020 were enrolled, and according to the antiviral therapy for HBeAg-positive CHB patients, they can be divided into group A with untreated HBeAg-positive CHB (HBeAg+ and HBV DNA+) patients, group B with treatment-experienced patients before HBeAg seroconversion (HBeAg+ and HBV DNA-), and group C with treatment-experienced patients after HBeAg seroconversion (HBeAg- and HBV DNA-). Peripheral blood HBV RNA load was measured at different periods, and its correlation with HBsAg and HBV DNA was analyzed. The t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between groups; a Pearson or Spearman correlation analysis was used to describe the correlation between two variables. Results The positive rates of HBV RNA in these three groups were 100% (22/22), 88.2% (15/17), and 22.7% (6/22), respectively. In group A, HBV RNA was positively correlated with HBsAg and HBV DNA (r=0.612 and 0.922, both P < 0.01), while in groups B and C, there was no correlation between HBV RNA and HBsAg. Group B had significantly higher levels of HBV RNA and HBsAg than group C (Z=-4.44 and -2.41, both P < 0.05). The HBV DNA-positive group had a significantly higher level of HBV RNA than the HBV DNA-negative group (Z=-6.16, P < 0.01). Conclusion After HBV DNA clearance achieved by antiviral therapy with nucleos(t)ide analogues in CHB patients, serum HBV RNA can still be detected in some of these patients. Since HBV RNA only comes from cccDNA in the liver, it can better reflect viral replication activity in the liver than HBV DNA and thus has a certain clinical value in the management of CHB patients. -
Key words:
- Hepatitis B, Chronic /
- Hepatitis B virus /
- RNA, Viral /
- DNA, Viral /
- Hepatitis B e Antigens
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表 1 纳入患者分组情况及基线资料
组别 例数 男 女 年龄(岁) HBeAg(+)、HBV DNA(+) 22 13 9 35.36±7.55 HBeAg(+)、HBV DNA(-) 17 11 6 39.35±7.98 HBeAg(-)、HBV DNA(-) 22 13 9 45.00±11.16 
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表 2 经治患者HBeAg阳性组与HBeAg阴性组临床资料比较
项目 HBeAg阳性组(n=17) HBeAg阴性组(n=22) 统计值 P值 男/女(例) 11/6 13/9 0.753 年龄(岁) 39.35±7.98 45.00±11.16 t=-1.77 0.086 HBV RNA阳性[例(%)] 15(88.2) 6(27.3) ＜0.001 HBV RNA(log10拷贝/mL) 4.05(3.01~5.18) 1.40(1.40~1.83) Z=-4.44 ＜0.001 HBsAg(log10IU/mL) 3.24(2.86~3.50) 2.76(2.07~3.35) Z=-2.41 0.016 ALT(U/L) 22.24±10.83 25.09±11.76 t=-0.78 0.442 AST(U/L) 23.00±4.48 23.9±14.23 t=-0.65 0.521
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表 3 HBV DNA阳性组与HBV DNA阴性组临床资料比较
项目 HBV DNA阳性组(n=22) HBV DNA阴性组(n=39) 统计值 P值 男/女(例) 13/9 24/15 χ2=0.035 0.851 年龄(岁) 35.36±7.55 42.54±10.18 t=-2.88 0.005 HBV RNA(log10拷贝/mL) 7.62(6.51~8.55) 1.94(1.40~4.04) Z=-6.16 ＜0.001 HBsAg(log10IU/mL) 3.94(3.26~4.23) 2.90(2.61~3.44) Z=-4.07 ＜0.001 ALT(U/L) 249.50(114.25~664.50) 20.00(16.00~31.00) Z=-6.45 ＜0.001 AST(U/L) 106.00(63.75~418.75) 23.00(21.00~27.00) Z=-6.45 ＜0.001 HBV DNA(log10IU/ml) 7.21±1.23 -
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[1] TANG L, COVERT E, WILSON E, et al. Chronic hepatitis B infection: A review[J]. JAMA, 2018, 319(17): 1802-1813. DOI: 10.1001/jama.2018.3795. [2] LIU J, LIANG W, JING W, et al. Countdown to 2030: Eliminating hepatitis B disease, China[J]. Bull World Health Organ, 2019, 97(3): 230-238. DOI: 10.2471/BLT.18.219469. [3] CUI FQ. Achievements in prevention and control of viral hepatitis since the founding of the people's Republic of China[J]. Int J Virol, 2019, 26(5): 289-292. DOI: 10.3760/cma.j.issn.1673-4092.2019.05.001.崔富强. 中国建国以来病毒性肝炎的防控成就[J]. 国际病毒学杂志, 2019, 26(5): 289-292. DOI: 10.3760/cma.j.issn.1673-4092.2019.05.001. [4] NASSAL M. HBV cccDNA: Viral persistence reservoir and key obstacle for a cure of chronic hepatitis B[J]. Gut, 2015, 64(12): 1972-1984. DOI: 10.1136/gutjnl-2015-309809. [5] KUMAR R, PÉREZ-DEL-PULGAR S, TESTONI B, et al. Clinical relevance of the study of hepatitis B virus covalently closed circular DNA[J]. Liver Int, 2016, 36(Suppl 1): 72-77. DOI: 10.1111/liv.13001. [6] ROUSSELET MC, MICHALAK S, DUPRÉ F, et al. Sources of variability in histological scoring of chronic viral hepatitis[J]. Hepatology, 2005, 41(2): 257-264. DOI: 10.1002/hep.20535. [7] LU FM, DOU XG, ZHANG WH, et al. Clinical significance of serum HBV RNA measurement in chronic hepatitis B patients[J]. J Clin Hepatol, 2018, 34(5): 934-938. DOI: 10.3969/j.issn.1001-5256.2018.05.005.鲁凤民, 窦晓光, 张文宏, 等. 慢性乙型肝炎患者血清HBV RNA检测的临床意义[J]. 临床肝胆病杂志, 2018, 34(5): 934-938. DOI: 10.3969/j.issn.1001-5256.2018.05.005. [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. 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] ROTH GA, ABATE D, ABATE KH, et al. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: A systematic analysis for the Global Burden of Disease Study 2017[J]. Lancet, 2018, 392(10159): 1736-1788. DOI: 10.1016/S0140-6736(18)32203-7. [10] GIERSCH K, ALLWEISS L, VOLZ T, et al. Serum HBV pgRNA as a clinical marker for cccDNA activity[J]. J Hepatol, 2017, 66(2): 460-462. DOI: 10.1016/j.jhep.2016.09.028. [11] TSUGE M, MURAKAMI E, IMAMURA M, et al. Serum HBV RNA and HBeAg are useful markers for the safe discontinuation of nucleotide analogue treatments in chronic hepatitis B patients[J]. J Gastroenterol, 2013, 48(10): 1188-1204. DOI: 10.1007/s00535-012-0737-2. [12] MAK LY, CLOHERTY G, WONG DK, et al. HBV RNA profiles in patients with chronic hepatitis B under different disease phases and antiviral therapy[J]. Hepatology, 2021, 73(6): 2167-2179. DOI: 10.1002/hep.31616. 期刊类型引用(17)
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