乙型肝炎病毒S基因的整合影响抗病毒治疗患者的乙型肝炎表

StephenW

J Gastroenterol Hepatol. 2017 Dec 20. doi: 10.1111/jgh.14075. [Epub ahead of print]
Integration of hepatitis B virus S gene impacts on hepatitis B surface antigen levels in patients with antiviral therapy.Hu B1,2, Wang R1,2, Fu J1,2, Su M1,2, Du M1,2, Liu Y1,2, Li H1,2, Wang H1,2, Lu F3, Jiang J1,2.
Author information
1Department of Infectious Disease, the First Affiliated Hospital of Guangxi Medical University, Nanning, China.2Guangxi Key Laboratory of AIDS Prevention and Treatment, Guangxi Medical University, Nanning, China.3Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center. Beijing, China.

AbstractBACKGROUND & AIMS: To investigate the impact of hepatitis B virus (HBV) S gene integration on serum hepatitis B surface antigen (HBsAg) levels in chronic hepatitis B (CHB) with long-term nucleos(t)ide analogue (NUCs) therapy.
METHODS: CHB patients who performed liver biopsy at baseline and treated with long-term NUCs therapy were recruited. The integration of HBV S gene in baseline liver biopsy specimen was detected by Alu-PCR method. Serum HBsAg levels were measured at baseline, the second year and the fourth year after NUCs therapy by Roche reagent respectively. Serum HBsAg levels between HBV S gene integrated group and non-integrated group were compared and analyzed.
RESULTS: Seventy patients were eligible for this study. Among them 11 (15.7%) were found HBV S gene integration in their baseline liver biopsy specimens. Similar significant decrease of HBsAg levels were found in both integrated and non-integrated groups (2.63 log IU/ml vs. 2.65 log IU/ml, P = 0.478) after the first two years NUCs therapy. Thereafter, the decrease of HBsAg level from 2 years to 4 years after therapy was largely unchanged in integrated group as compared to that in non-integrated group (2.53 log IU/ml vs. 0.1 log IU/ml, P = 0.002), with statistically difference.
CONCLUSIONS: Serum HBsAg could be originated from the expression of the integrated HBV S gene in patients with S gene integration, which implicated the limitations when regarding HBsAg as a surrogate biomarker of cccDNA activity and as an indicator of safe NUCs discontinuation.

This article is protected by copyright. All rights reserved.

KEYWORDS: HBV S gene; HBsAg; hepatitis B virus; integration

PMID:29266382DOI:10.1111/jgh.14075

StephenW

J Gastroenterol Hepatol。 2017年12月20日doi：10.1111 / jgh.14075。 [电子版提前打印]
乙型肝炎病毒S基因的整合影响抗病毒治疗患者的乙型肝炎表面抗原水平。
胡B1,2，王R1,2，付1 1,2，苏M1,2，杜M1,2，刘Y1,2，李H1,2，王H1,2，陆F3，姜1 1,2。
作者信息
抽象
背景与目的：

探讨乙型肝炎病毒（HBV）S基因整合对慢性乙型肝炎（CHB）患者血清乙型肝炎表面抗原（HBsAg）水平的影响，探讨长期核苷（酸）类似物（NUCs）治疗对乙型肝炎表面抗原（HBsAg）
方法：

CHB患者在基线进行肝活检并接受长期NUC治疗。采用Alu-PCR方法检测HBV S基因在基线肝活检标本中的整合情况。在基线，罗氏试剂NUC治疗后的第二年和第四年测定血清HBsAg水平。比较和分析HBV S基因整合组与非整合组之间的血清HBsAg水平。
结果：

70名患者有资格参加这项研究。其中11例（15.7％）在基线肝活检标本中发现HBV S基因整合。在NUCs治疗的头两年，整合组和非整合组的HBsAg水平同样显着下降（2.63 log IU / ml比2.65 log IU / ml，P = 0.478）。治疗后2年至4年HBsAg水平下降与未整合组相比差异无统计学意义（2.53 log IU / ml vs. 0.1 log IU / ml，P = 0.002）区别。
结论：

血清HBsAg可能来源于S基因整合患者整合型HBV S基因的表达，这提示HBsAg作为cccDNA活性的替代生物标志物和作为安全NUCs终止指标的局限性。

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关键词：

HBV S基因;乙肝表面抗原;乙肝病毒;积分

结论：
29266382
DOI：
10.1111 / jgh.14075

StephenW

很有意义的研究!

"In conclusion, the results of this study suggest that, in addition to relying on cccDNA
transcriptional   expression   of   the   classical   pathway, the   production   of  HBsAg
can alternatively  from  the integrated HBV  S  gene,which indicating  that there  is  a  certain probability of false positive to use HBsAg levels as a marker of cccDNA aactivity, also the clearance of  HBsAg  as  a  unique  endpoint  of  clinical  cure  for  CHB  patients  has some limitation. "
"综上所述，本研究结果提示，除依靠cccDNA外
经典途径的转录表达，HBsAg的产生
也可能来自整合的HBV S基因，表明用HBsAg水平作为cccDNA活性的标志物存在一定的假阳性概率，同时作为CHB患者临床治疗独特终点的HBsAg清除率也有一定的局限性。"

Study showed:
1. Continual decrease of cccDNA during NUC treatment
2.  cccDNA maybe zero (i.e. cured) but HBsAg still positive because of integrated S gene in the liver cells.

研究显示：
1.在NUC治疗期间，cccDNA持续减少
2. cccDNA可能为零（即治愈），但由于肝细胞中整合的S基因，HBsAg仍然为阳性。