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556
Levels of Intrahepatic HBV RNA Served As a
Potential Virological Set Point for Withdrawal of
NA Therapy
Yiqi Yu1, Jing Wang1, Guojun Li2, Chuan Shen3, Yuxian
Huang1, Jiming Zhang4 and Wenhong Zhang1, (1)Infectious
Diseases, Huashan Hospital, (2)Hepatology, The Second
Hospital of Yinzhou of Ningbo, (3)Infectious Diseases, The
Third Hospital of Hebei Medical University, (4)Department
of Infectious Diseases, Huashan Hospital Affiliated to Fudan
University
Background: Viral rebound developed after nucleos(t)
ide analogue (NA) withdrawal in most patients who had
even achieved suppression of serum HBV DNA to an
undetectable level. The unresolved question regarding the
optimal virological set point for the spontaneous control of
HBV replication remained. We evaluated whether levels of
intrahepatic HBV RNA served as a potential virological set
point for safety withdrawal of NA therapy. Methods: We
compared the levels of the viral replicative forms of HBV in
serum and liver samples between HBeAg-negative patients
who had been successfully treated with entecavir (ETV) for >1
year and inactive carriers. Treatment-naive HBeAg-negative
chronic patients experiencing active hepatitis were also
included for comparison. Results: Significantly lower levels
of serum HBV RNA were observed in ETV-treated HBeAgnegative
patients (2.57 log10 copies/mL, range = 2.00-3.73
log10 copies/mL) than in treatment-naive patients (4.74 log10
copies/mL, range = 2.76-5.75 log10 copies/mL; P < 0.0001) as
shown in Fig. 1A. Serum HBV RNA (<200 copies/mL) was
undetectable in 6/22 (27.3%) ETV-treated patients. However,
cases with undetectable serum HBV RNA were more frequent
(12/16, 75%) among inactive carriers (Fig. 1A, P = 0.0076).
In liver biopsies, intrahepatic HBV RNA was detectable for
all patients. The intrahepatic HBV RNA levels of patients
treated with ETV (2.76 log10 copies/mL, range = 0.30-4.40
log10 copies/mL) were not significantly lower (P = 0.2786)
than those of treatment-naive patients (2.06 log10 copies/
mL, range = 1.09-3.10 log10 copies/mL), and remained higher
than those of inactive carriers (1.21 log10 copies/mL, range =
0-1.87 log10 copies/mL; P = 0.0019) (Fig. 1B). In comparison
to treatment-naive patients, levels of intrahepatic total HBV
DNA (Fig. 1C) and covalently closed circular DNA (cccDNA)
(Fig. 1D) were significantly decreased in ETV-treated patients
and inactive carriers, but no differences were observed
between the latter two groups. Conclusion: These data
suggested that although NA therapy induced the remission
of liver disease and reduced the size of the cccDNA pool, the
levels of intrahepatic HBV RNA could not be reduced to the
comparably low levels of inactive carriers. Lower levels of
intrahepatic HBV RNA approaching those of inactive carriers,
might also be considered a useful and safety virological
endpoint for cessation of NA therapy. |
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发表于 2018-10-25 16:21