738
PERSISTENTLY DETECTABLE SERUM HBV DNA AND PGRNA
IS ASSOCIATED WITH SUBSEQUENT HCC DEVELOPMENT IN
CHRONIC HEPATITIS B PATIENTS RECEIVING CHRONIC NRTI
TREATMENT
Lung Yi Mak1, Qi Huang2, Ka Ho Danny Wong3, Ran Yan2,
Lea Ouyang2, James Fung3, Wai Kay Walter Seto4 and Man
Fung Yuen3, (1)State Key Laboratory for Liver Research,
The University of Hong Kong, (2)Assembly Biosciences,
(3)Medicine, The University of Hong Kong, (4)State Key
Laboratory of Liver Research, The University of Hong Kong
Background: Although antiviral therapy reduces the risk
of hepatocellular carcinoma (HCC) in chronic hepatitis B
(CHB) patients, HCC risk is not eliminated in those achieving
undetectable serum hepatitis B virus (HBV) DNA by standard
assays We aimed to assess whether HBV DNA and pgRNA
detected by highly sensitive assays are associated with HCC
development in a retrospective case-control study Methods:
A total of 104 patients [52 HCC cases and 52 non-HCC
controls (matched with age, gender and treatment duration)
on ≥3 years of entecavir (ETV) with undetectable HBV DNA
by Cobas Taqman assay version 2 0 (Roche Diagnostics;
lower limit of detection [LLOD] 20 IU/mL) were included
Stored serum from 3 (-3 years), 2 (-2 years) and 1 (-1 year)
prior to HCC diagnosis or last follow-up (LFU) were assessed
using highly sensitive HBV DNA and pgRNA assays Total
viral nucleic acid was extracted and subjected to HBV DNA
and total nucleic acid (HBV DNA + pgRNA) measurements,
Detection of HBV DNA was performed using a semiquantitative
PCR assay with LLOD of 10 IU/mL Quantitation
of pgRNA was derived from the difference between the total
nucleic acid levels and HBV DNA levels, with a lower limit of
quantification (LLOQ) of 300 copies/mL and LLOD of 10 IU/
mL Results: Among the 104 patients (59 6% male, median
age 61 2 years old, duration of ETV 45 5 months), 93 and 96
had retrievable samples at -3 and -2 years prior to HCC or
LFU, respectively For HCC patients, only 34 1%, 38 5% and
38 5% had undetectable HBV DNA and only 4 3%, 10 3% and
9 6% had undetectable pgRNA by the highly sensitive assays
at time -3, -2 and -1 year, respectively For non-HCC patients,
only 43 9%, 51% and 65 4% had undetectable HBV DNA and
only 11 1%, 22 4% and 36 5% had undetectable pgRNA by the
highly sensitive assays at time -3, -2 and -1 year, respectively
(Figure 1). The median pgRNA was significantly higher in
patients with HCC compared to those without HCC at -3 years
[(1857 (IQR 300 – 172500) vs 300 (IQR 300 – 1819) copies/
mL, p=0 005) Detectable viral nucleic acid at all 3 time points
was significantly associated with HCC development (log rank
P<0 05 for all 3 comparisons) Conclusion: More than half of
CHB patients on ETV with HBV DNA < LLOQ by a standard
assay had persistent HBV DNA and pgRNA detected by highly
sensitive assays which was associated with subsequent HCC
development More profound viral suppression is needed for
further reduction of HCC risk in CHB patients. 作者: StephenW 时间: 2020-10-23 16:43