AASLD2020[723]慢性循環HBV RNA定量 乙型肝炎患者隨訪。

StephenW

723
CIRCULATING HBV RNA QUANTIFICATION IN CHRONIC
HEPATITIS B PATIENTS FOLLOW-UP.
Maria Francesca Cortese1,2, Mar Riveiro Barciela3,4, Sara
Sopena1, Adriana Palom5, David Tabernero1,4, Francisco
Rodriguez-Algarra6, Ariadna Rando7, Luisa Roade4,5, Roser
Maria Ferrer-Costa8, Alison Kuchta9, Rafael Esteban-Mur10,11,
Maria Asuncion Buti Ferret5,10 and Francisco Rodriguez
Frías1,2,4, (1)Biochemistry and Microbiology/Liver Pathology
Unit, Vall D’hebron University Hospital, (2)Liver Unit, Vall
D’hebron Research Institute, (3)Liver Unit, Internal Medicine
Department. Hospital Universitari Vall d’Hebron, Barcelona,
Spain, University Hospital Vall D’hebron, (4)Centro De
Investigación Biomédica En Red, Enfermedades Hepáticas y
Digestvas (CIBERehd), Instituto De Salud Carlos III, Madrid,
Spain, (5)Liver Unit, Internal Medicine Department. Hospital
Universitari Vall d’Hebron, Barcelona, Spain, (6)The Blizard
Institute- Barts and the London School of Medicine and
Dentistry, Queen Mary University of London, (7)Virology Unit,
Microbiology Department, Hospital Universitari Vall D’hebron,
(8)Department of Biochemistry, Vall D’hebron University
Hospital, Vall D’hebron University Hospital, (9)Roche
Molecular Systems, Inc., (10)Ciberehd, Instituto Carlos III,
Madrid, (11)Liver Unit, Hospital Vall D’hebron
Background: Circulating HBV RNA is a marker of intrahepatic
viral expression that could be useful for monitoring chronic
hepatitis B patients virally suppressed on NUC therapy
Traditionally, quantification has been carried out using various
unstandardized and low sensitive techniques resulting in
unreproducible data Here we present a highly sensitive
novel automated procedure used to identify the utility of
circulating HBV RNA in chronic hepatitis management
Methods: 119 HBV-patients (56 treated and 63 treatmentnaïve)
were included in the study Plasma samples were
collected at different time points Circulating HBV RNA and
DNA were quantified by real-time PCR using the automated
cobas®6800 analyzer (Roche HBV RNA assay- linear range
of 10-1E9 copies/mL; LLOQ of 10 copies/mL) HBcrAg was
quantified by Lumipulse G chemilumiscent assay (Fujirebio)
and HBsAg was quantified by chemiluminescent enzyme
immunoassays (cobas®8000) Univariate and multivariate
analysis were conducted considering the first sample with
undetectable HBV DNA Results: A total of 475 samples were
collected (267 and 208 for naïve and treated patients) during
a median of 3[1 3-3 4] years of follow-up in naïve cases and
2 4 [0 9-5 24] years of treatment HBV RNA was detectable
in 151 samples, including 40/170 samples from treated
patients with undetectable HBV DNA In naïve patients, HBV
DNA was 2 9log higher than HBV RNA throughout follow-up
(p<0 01) and both markers were correlated with one another
(r=0 7, p<0 01) In NUC virally suppressed patients, HBV
RNA showed a titer of 0 6log higher than HBV DNA, mainly
during the first years of treatment. Multivariate analysis
showed that a decreasing or undetectable HBV RNA titer
during treatment was a positive predictor of HBsAg<1000IU/
mL (p=0 04) outcome No relation was observed between
undetectable HBcrAg (<2 5logU/mL) and HBsAg<1000 IU/mL
outcome Conclusion: Automated HBV RNA quantification
using the cobas®6800 is a sensitive technique that enables
a reproducible viral RNA quantification. In naïve patients the
ratio between viral DNA and RNA was higher than previously
reported The presence of detectable HBV RNA virally
suppressed patients is suggestive of persistent transcription
from cccDNA reservoir These data suggest that undetectable
or decreasing HBV RNA levels are more predictive of an
HBsAg<1000 IU/mL outcome than an undetectable HBcrAg
titer Funding: Instituto de Salud Carlos III (grant PI17/02233),
co-financed by the European Regional Development Fund
(ERDF)

StephenW

723
慢性循環HBV RNA定量
乙型肝炎患者隨訪。
瑪麗亞·弗朗西斯卡·科爾蒂斯1,2，馬爾·里維羅·巴西埃拉3,4，薩拉
Sopena1，Adriana Palom5，David Tabernero1,4，Francisco
Rodriguez-Algarra6，Ariadna Rando7，Luisa Roade4,5，Roser
Maria Ferrer-Costa8，Alison Kuchta9，Rafael Esteban-Mur10,11，
瑪麗亞·亞松森·布蒂·費雷5,10和弗朗西斯科·羅德里格斯
Frías1,2,4，（1）生化與微生物學/肝髒病理學
瓦勒德希伯倫大學醫院病房，（2）瓦勒肝髒病房
D'hebron研究所，（3）內科肝病科
部門。巴塞羅那希伯倫大學瓦里達希伯倫分校
西班牙，瓦爾·德希布倫大學醫院，（4）
生物醫學研究會（EnfermedadesHepáticasy）
Digestvas（CIBERehd），馬德里薩洛德·卡洛斯三世研究所，
西班牙，（5）內科肝病科。醫院
西班牙巴塞羅那的瓦拉德赫布倫大學（6）
研究所-巴茨和倫敦醫學院
倫敦瑪麗皇后大學牙科系（7）病毒學科，
Universitari Vall D’hebron醫院微生物學系，
（8）瓦萊德希伯倫大學生物化學系
瓦萊德黑布倫大學醫院醫院，（9）羅氏
Molecular Systems，Inc.（10），Ciberehd，Carlos III研究所，
馬德里（11）瓦爾·德希布倫醫院肝病部門
背景：循環中的HBV RNA是肝內標誌物
病毒表達可用於監測慢性
乙肝患者在NUC治療中受到病毒抑制
傳統上，量化使用
不規範和低敏感度的技術導致
無法再現的數據在這裡，我們提出了一個高度敏感的
新穎的自動化程序，用於識別
循環HBV RNA在慢性肝炎管理中
方法：119名乙肝患者（56例接受治療，63例未接受治療）
包括在研究中
在不同時間點收集循環HBV RNA和
使用自動化的實時PCR定量DNA
cobas®6800分析儀（Roche HBV RNA分析-線性範圍
10-1E9拷貝/ mL L拷貝為10拷貝/ mL）
通過Lumipulse G化學發光測定（Fujirebio）進行定量
並用化學發光酶定量HBsAg
免疫測定（cobas®8000）單變量和多變量
考慮第一個樣品進行分析
無法檢測到HBV DNA結果：總共475個樣本
在（
單純病例的平均隨訪時間為3 [1 3-3 4]年，
2 4 [0 9-5 24]年的治療可檢測到HBV RNA
在151個樣本中，包括來自處理過的40/170個樣本
HBV DNA檢測不到的患者
在整個隨訪期間，DNA比HBV RNA高2 9log
（p <0 01），並且兩個標記都相互關聯
（r = 0 7，p <0 01）在NUC病毒抑制的患者中，HBV
RNA的效價比HBV DNA高0 6log
在治療的頭幾年。多元分析
表明HBV RNA滴度降低或無法檢測
治療期間是HBsAg <1000IU /
mL（p = 0 04）結果之間沒有相關性
HBcrAg（<2 5logU / mL）和HBsAg <1000 IU / mL
結果結論：自動化的HBV RNA定量
使用cobas®6800是一項敏感技術
可重複的病毒RNA定量。在天真的患者中
病毒DNA和RNA之間的比率比以前更高
報告病毒中可檢測到的HBV RNA的存在
受抑制的患者提示持續轉錄
來自cccDNA儲庫的數據這些數據表明無法檢測
或降低HBV RNA水平更能預測
HBsAg <1000 IU / mL比未檢測到的HBcrAg
資金資助：薩洛德·卡洛斯三世研究所（PI17 / 02233贈款），
由歐洲區域發展基金共同資助
（ERDF）