Application of Hepatitis B Virus Surface Antigen Quantification and Its Impact Factors in Patients with Chronic Hepatitis B during Nucleot(s)ide Analogues Treatment from Xinjiang_West China Medical Journal

Authors：

 WangXiaobo , GuoFeng , WangXiaozhong ,  WangYan

Department of Hepatology, Traditional Chinese Medical Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang 830000, P. R. China;

Corresponding author：

WangYan, Email: wangyanxinjiang@aliyun.com

Keywords：

Nucleot(s)ide analogues; Chronic hepatitis B; Hepatitis B virus surface antigen quantification

DOI：

10.7507/1002-0179.201600495

Video：

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Objective To study the value of hepatitis B virus surface antigen (HBsAg) in the evaluation of antiviral efficacy and its influencing factors under a complex population background resulting from various nationalities in Xinjiang. Methods We retrospectively analyzed patients with chronic hepatitis B (CHB) admitted and administrated with nucleot(s)ide analogues (NAs) for the first time in Traditional Chinese Medical Hospital of Xinjiang Uygur Autonomous Region from January 2012 to August 2013. The biological, virological, and serological responses were analyzed as well as the possible factors related to HBsAg levels and its reduction levels. Results There were 63 CHB patients enrolled. After 48 weeks' treatment, all patients achieved biological response, and 59 of them achieved complete virological response in spite of 4 patients with partial response. In all the 30 hepatitis B virus e antigen (HBeAg) positive patients, 5 achieved HBeAg seroconversion. After correlation and regression analysis, it turned out that the history (P=0.033) and HBeAg levels at week 48 (P<0.001) were independent impact factors for HBsAg level at week 48. And the reduction degree of HBsAg at week 48 was influenced by HBsAg at week 48. In 21 patients counting to week 72 maintaining biological response, 18 achieved complete virological response. Unfortunately, all 8 HBeAg positive patients encountered no HBeAg loss or seroconversion. After correlation and regression analysis, it turned out that HBsAg level at week 72 was influenced by HBsAg at week 48 (r=0.700, P<0.001). And the decline degree of HBsAg at week 72 was related to baseline HBsAg level. Conclusion Satisfactory efficacy can be achieved via NAs treatment in CHB patients. But when HBsAg is used separately as an indicator for therapeutic efficacy, we should be aware that intrahepatic covalently closed circular DNA (cccDNA) is not only the impact factor of HBsAg variation, the history, the variations of HBeAg and HBsAg itself during the treatment should also be considered.

Citation： WangXiaobo, GuoFeng, WangXiaozhong, WangYan. Application of Hepatitis B Virus Surface Antigen Quantification and Its Impact Factors in Patients with Chronic Hepatitis B during Nucleot(s)ide Analogues Treatment from Xinjiang. West China Medical Journal, 2016, 31(11): 1801-1806. doi: 10.7507/1002-0179.201600495 Copy

1.	张琳, 吴峰, 石理兰, 等. HBV携带者血清病毒标志物和HBV DNA与肝组织中HBVcccDNA相关性的研究[J].中华实验和临床病毒学杂志, 2011, 25(2):112-113.
2.	Zheng Q, Zhu YY, Chen J, et al. Decline in intrahepatic cccDNA and increase in immune cell reactivity after 12 weeks of antiviral treatment were associated with HBeAg loss[J].J Viral Hepat, 2014, 21(12):909-916.
3.	李韦杰, 李伯安, 赵景民, 等. 54例慢性乙型肝炎患者肝组织乙型肝炎病毒共价闭合环状DNA与血清HBsAg定量检测结果分析[J].中华肝脏病杂志, 2011, 19(11):815-817.
4.	Chuaypen N, Sriprapun M, Praianantathavorn K, et al. Kinetics of serum HBsAg and intrahepatic cccDNA during pegylated interferon therapy in patients with HBeAg-positive and HBeAg-negative chronic hepatitis B[J/OL].J Med Virol, 2016. https://dx.doi.org/10.1002/jmv.24601.
5.	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(2010年版)[J].中国肝脏病杂志:电子版, 2011, 19(1):13-24.
6.	王文真, 卢丽霞, 王丽春. 慢性乙型肝炎核苷类似物抗病毒治疗应答的影响因素[J].华西医字, 2014, 29(9):776-779.
7.	李莹, 韩涛, 马晓艳, 等. 原发性肝细胞癌患者乙型肝炎病毒表面抗原与肝组织HBVDNA水平的相关性[J].中国病毒病杂志, 2011, 36(1):32-34.
8.	Volz T, Lutgehetmann M, Wachtler P, et al. Impaired intrahepatic hepatitis B virus productivity contributes to low viremia in most HBeAg-negative patients[J].Gastroenterology, 2007, 133(3):843-852.
9.	Wursthorn K, Lutgehetmann M, Dandri M, et al. Peginterferon alpha-2b plus adefovir induce strong cccDNA decline and HBsAg reduction in patients with chronic hepatitis B[J].Hepatology, 2006, 44(3):675-684.
10.	Nguyen T, Thompson AJ, Bowden S, et al. Hepatitis B surface antigen levels during the natural history of chronic hepatitis B:a perspective on Asia[J].J Hepatol, 2010, 52(4):508-513.
11.	Jaroszewicz J, Calle Serrano B, Wursthorn K, et al. Hepatitis B surface antigen (HBsAg) levels in the natural history of hepatitis B virus (HBV)-infection:a European perspective[J].J Hepatol, 2010, 52(4):514-522.
12.	Chan HL, Wong VW, Wong GL, et al. A longitudinal study on the natural history of serum hepatitis B surface antigen changes in chronic hepatitis B[J].Hepatology, 2010, 52(4):1232-1241.
13.	Su TH, Hsu CS, Chen CL, et al. Serum hepatitis B surface antigen concentration correlates with HBV DNA level in patients with chronic hepatitis B[J].Antivir Ther, 2010, 15(8):1133-1139.
14.	Liaw YF, Brunetto MR, Hadziyannis S. The natural history of chronic HBV infection and geographical differences[J].Antivir Ther, 2010, 15(Suppl 3):25-33.
15.	Lin C, Zou H, Wang S. Hepatitis B e antigen seroconversion is related with the function of dendritic cells in chronic hepatitis B virus infection[J].Gastroenterol Res Pract, 2014, 2014:413952.
16.	Marcellin P, Lada O, Asselah T. Treatment of chronic hepatitis B with the combination of pegylated interferon with lamivudine[J].Hepatol Res, 2007, 37(s1):S55-S61.
17.	Sonneveld MJ, Rijckborst V, Boucher CA, et al. Prediction of sustained response to peginterferon alfa-2b for hepatitis B e antigen-positive chronic hepatitis B using on-treatment hepatitis B surface antigen decline[J].Hepatology, 2010, 52(4):1251-1257.

1. 张琳, 吴峰, 石理兰, 等. HBV携带者血清病毒标志物和HBV DNA与肝组织中HBVcccDNA相关性的研究[J].中华实验和临床病毒学杂志, 2011, 25(2):112-113.
2. Zheng Q, Zhu YY, Chen J, et al. Decline in intrahepatic cccDNA and increase in immune cell reactivity after 12 weeks of antiviral treatment were associated with HBeAg loss[J].J Viral Hepat, 2014, 21(12):909-916.
3. 李韦杰, 李伯安, 赵景民, 等. 54例慢性乙型肝炎患者肝组织乙型肝炎病毒共价闭合环状DNA与血清HBsAg定量检测结果分析[J].中华肝脏病杂志, 2011, 19(11):815-817.
4. Chuaypen N, Sriprapun M, Praianantathavorn K, et al. Kinetics of serum HBsAg and intrahepatic cccDNA during pegylated interferon therapy in patients with HBeAg-positive and HBeAg-negative chronic hepatitis B[J/OL].J Med Virol, 2016. https://dx.doi.org/10.1002/jmv.24601.
5. 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(2010年版)[J].中国肝脏病杂志:电子版, 2011, 19(1):13-24.
6. 王文真, 卢丽霞, 王丽春. 慢性乙型肝炎核苷类似物抗病毒治疗应答的影响因素[J].华西医字, 2014, 29(9):776-779.
7. 李莹, 韩涛, 马晓艳, 等. 原发性肝细胞癌患者乙型肝炎病毒表面抗原与肝组织HBVDNA水平的相关性[J].中国病毒病杂志, 2011, 36(1):32-34.
8. Volz T, Lutgehetmann M, Wachtler P, et al. Impaired intrahepatic hepatitis B virus productivity contributes to low viremia in most HBeAg-negative patients[J].Gastroenterology, 2007, 133(3):843-852.
9. Wursthorn K, Lutgehetmann M, Dandri M, et al. Peginterferon alpha-2b plus adefovir induce strong cccDNA decline and HBsAg reduction in patients with chronic hepatitis B[J].Hepatology, 2006, 44(3):675-684.
10. Nguyen T, Thompson AJ, Bowden S, et al. Hepatitis B surface antigen levels during the natural history of chronic hepatitis B:a perspective on Asia[J].J Hepatol, 2010, 52(4):508-513.
11. Jaroszewicz J, Calle Serrano B, Wursthorn K, et al. Hepatitis B surface antigen (HBsAg) levels in the natural history of hepatitis B virus (HBV)-infection:a European perspective[J].J Hepatol, 2010, 52(4):514-522.
12. Chan HL, Wong VW, Wong GL, et al. A longitudinal study on the natural history of serum hepatitis B surface antigen changes in chronic hepatitis B[J].Hepatology, 2010, 52(4):1232-1241.
13. Su TH, Hsu CS, Chen CL, et al. Serum hepatitis B surface antigen concentration correlates with HBV DNA level in patients with chronic hepatitis B[J].Antivir Ther, 2010, 15(8):1133-1139.
14. Liaw YF, Brunetto MR, Hadziyannis S. The natural history of chronic HBV infection and geographical differences[J].Antivir Ther, 2010, 15(Suppl 3):25-33.
15. Lin C, Zou H, Wang S. Hepatitis B e antigen seroconversion is related with the function of dendritic cells in chronic hepatitis B virus infection[J].Gastroenterol Res Pract, 2014, 2014:413952.
16. Marcellin P, Lada O, Asselah T. Treatment of chronic hepatitis B with the combination of pegylated interferon with lamivudine[J].Hepatol Res, 2007, 37(s1):S55-S61.
17. Sonneveld MJ, Rijckborst V, Boucher CA, et al. Prediction of sustained response to peginterferon alfa-2b for hepatitis B e antigen-positive chronic hepatitis B using on-treatment hepatitis B surface antigen decline[J].Hepatology, 2010, 52(4):1251-1257.

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Application of Hepatitis B Virus Surface Antigen Quantification and Its Impact Factors in Patients with Chronic Hepatitis B during Nucleot(s)ide Analogues Treatment from Xinjiang

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