AASLD2018[458E]HBV RNA仍可在血清中定量分析 抑郁症后HbeAg阴性患

StephenW

s 458E
HBV RNA Can Still be Quantified in Serum in
HbeAg Negative Patients after Suppression of
HBV DNA By Nuleos(t)Ide Analogues for up to
10 Years
Florian van Bömmel1, Danilo Deichsel1, Alessandro Loglio2,
Floriana Facchetti2, Thomas Berg1 and Pietro Lampertico3,
(1)Department of Gastroenterology and Rheumatology,
Section of Hepatology, University Hospital Leipzig, (2)
Division of Gastroenterology and Hepatology, CRC “a. M. e a.
Migliavacca” Center for Liver Disease Fondazione Irccs Ca’
Granda Ospedale Maggiore Policlinico, University of Milan,
(3)University of Milan
Background: Hepatitis B virus (HBV) RNA is a new serological
marker that correlates with cccDNA levels. Recently, it has
been shown that HBV RNA levels remain detectable in
HBeAg positive patients in spite of suppression of HBV DNA
by treatment with nucleos(t)ide analogues (NAs). However,
in HBeAg negative patients the kinetics of HBV RNA during
long term NA treatment are yet unknown. The aim of our study
was to examine whether HBV RNA may still be detectable
after long term treatment with NA. Methods: A total of 96
patients with HBeAg negative chronic HBV infection (mean
age 65±9 [range, 40-84] years, 74 (77%) male, 50 (52%)
with liver cirrhosis, 96 (100%) HBV genotype D) who had
achieved undetectable HBV DNA levels for > 5 years (mean
88±32 [range, 61-136] months) during NA treatment were
retrospectively analyzed. All patients were HBeAg negative at
the start of NA treatment and had achieved normal ALT during
NA treatment over at least 5 years. Thirty-eight patients had
achieved undetectable HBV DNA for longer than 8 and 9 for
longer than 10 years. The current treatment consisted either
of tenofovir (TDF, n=90) or entecavir (ETV, n=6) and had been
conducted for a mean duration of 52±11 [range, 6-81] months.
HBV RNA levels were measured from serum samples stored
at -20°C using a specific real-time PCR technique (lower limit
of detection (LOD) 160 copies/mL). HBV DNA was quantified
by real time PCR (Roche, LOD 9 IU/mL), and HBsAg by
ELISA (Abbott Architect, LOD 0.5 IU/mL). Results: HBV
RNA levels were detectable in 49/96 (49%) of samples by a
mean of 2.2±0.7 (range, 0.93-3.97) log10 copies/mL including
20 (41%) patients with cirrhosis. At the same time point,
mean HBsAg levels were 806±1,465 [range, 1-11,781] IU/
mL. One of the patients with detectable HBV RNA received
long term treatment with steroids. Detection of HBV RNA was
not associated with HBsAg levels, patient age, presence of
cirrhosis, development of hepatocellular carcinoma, duration
of NA treatment or duration of undetectable HBV DNA (p=n.s.).
Conclusion: In HBeAg negative patients achieving long term
suppression of HBV DNA during NA treatment HBV RNA can
frequently be detected even after long treatment periods.
Therefore, HBV RNA in serum may serve as response marker
for future treatments in those patients.

StephenW

s 458E
HBV RNA仍可在血清中定量分析
抑郁症后HbeAg阴性患者
HBV DNA通过Nuleos（t）Ide类似物达到
10年
FlorianvanBömmel1，Danilo Deichsel1，Alessandro Loglio2，
Floriana Facchetti2，Thomas Berg1和Pietro Lampertico3，
（1）胃肠病学和风湿病学系，
莱比锡大学附属医院肝病科，（2）
CRC的消化内科和肝病学科“a。 M. e。
Migliavacca“肝病中心Irccs Ca”
米兰大学Granda Ospedale Maggiore Policlinico
（3）米兰大学
背景：乙型肝炎病毒（HBV）RNA是一种新的血清学
与cccDNA水平相关的标记物。最近，它有
已经证明HBV RNA水平仍然可检测到
HBeAg阳性患者尽管抑制了HBV DNA
通过用核苷（t）ide类似物（NA）处理。然而，
在HBeAg阴性患者中HBV RNA的动力学过程
长期NA治疗尚不清楚。我们研究的目的
是为了检查HBV RNA是否仍然可检测到
用NA长期治疗后。方法：共96项
HBeAg阴性慢性HBV感染患者（平均值
年龄65±9 [范围，40-84]岁，74（77％）男性，50（52％）
肝硬化患者，96例（100％）HBV基因型D）患者
实现检测不到HBV DNA水平超过5年（平均值
在NA治疗期间，88±32 [范围，61-136]个月）
回顾性分析。所有患者均为HBeAg阴性
NA治疗的开始并且在期间达到了正常的ALT
NA治疗至少5年。 38名患者
实现了不可检测的HBV DNA超过8和9
超过10年。目前的治疗方法包括
替诺福韦（TDF，n = 90）或恩替卡韦（ETV，n = 6）和曾经
平均持续时间为52±11 [范围，6-81]个月。
从储存的血清样品测量HBV RNA水平
在-20°C使用特定的实时PCR技术（下限
检测（LOD）160拷贝/ mL）。定量HBV DNA
通过实时PCR（罗氏，LOD 9 IU / mL）和HBsAg
ELISA（Abbott Architect，LOD 0.5 IU / mL）。结果：HBV
通过a。在49/96（49％）的样品中可检测到RNA水平
平均值为2.2±0.7（范围，0.93-3.97）log10拷贝/ mL，包括
20例（41％）肝硬化患者。在同一时间点，
平均HBsAg水平为806±1,465 [范围，1-11,781] IU /
毫升。其中一名患者接受了可检测的HBV RNA
长期使用类固醇治疗。检测HBV RNA是
与HBsAg水平无关，患者年龄，存在
肝硬化，肝细胞癌的发展，持续时间
NA治疗或不可检测的HBV DNA持续时间（p = n.s。）。
结论：HBeAg阴性患者长期服用
在NA治疗期间抑制HBV DNA HBV RNA可以
即使经过长时间的治疗，也经常会被发现
因此，血清中的HBV RNA可以作为反应标记物
对于那些患者的未来治疗。