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.作者: StephenW 时间: 2018-10-23 15:37