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Predictability of Serum Hbcrag, HBsAg and
Interferon Inducible Protein 10 (IP10) Levels
in Non-Cirrhotic Hbeag-Negative Chronic
Hepatitis B Patients Who Discontinue Entecavir
(ETV) or Tenofovir (TDF) Therapy: Results from
the Prospective Daring-B Study
Margarita Papatheodoridi1, Emilia Hadziyannis2, Francoise
Berby3, Eirini Rigopoulou4, Kalliopi Zachou4, Barbara Testoni3,
Aggeliki Lyberopoulou4, Nikolaos K. Gatselis5, Ioannis
Vlachogiannakos6, Spilios Manolakopoulos1,7, George N.
Dalekos5, Fabien Zoulim8 and George V. Papatheodoridis6, (1)
Department of Gastroenterology, Medical School of National
and Kapodistrian University of Athens, Laiko General Hospital
of Athens, (2)2nd Department of Internal Medicine, Medical
School of National & Kapodistrian University of Athens,
Hippokratio General Hospital of Athens, (3)Department of
Hepatology, Hospices Civils De Lyon, Crcl-Inserm U1052,
Lyon University, (4)Department of Internal Medicine, Thessalia
University Medical School, (5)Department of Medicine
and Research Laboratory of Internal Medicine, University
of Thessaly, (6)Department of Gastroenterology, Medical
School of National & Kapodistrian University of Athens, Laiko
General Hospital, Athens, (7)2nd Academic Department of
Internal Medicine, Medical School of National & Kapodistrian
University of Athens, Hippokratio General Hospital of Athens,
(8)Department of Hepatology, Croix Rousse Hospital,
Hospices Civils De Lyon, France
Background: Discontinuation of ETV/TDF is discussed as
a strategy to induce HBsAg loss in HBeAg-negative chronic
hepatitis B (CHBe-) but is also associated with variable relapse/
retreatment rates. We examined predictors of HBsAg loss and
retreatment in non-cirrhotic CHBe- patients who discontinued
long-term effective ETV/TDF therapy. Methods: We included
60 CHBe- patients without pre-treatment cirrhosis who were
prospectively enrolled and followed in the DARING-B study.
All were followed for ≥12 months (mos) or until retreatment
(baseline, monthly for first 3 mos and every 2/3 mos thereafter
for detectable/undetectable HBVDNA). Main retreatment
criteria were ALT>10xULN, ALT>3xULN & HBV DNA>100,000
IU/mL, ALT>ULN & HBV DNA>2000 IU/mL on 3 sequential
occasions. HBcrAg, HBsAg and IP10 levels were determined
by enzyme immunoassays (Lumipulse, Fujirebio; Elecsys,
Roche; Instant Elisa, eBioscience) in serial serum samples
stored at each visit after stopping ETV/TDF. Results: Mean
patient follow-up has been 19±9 mos. The cumulative rates
of HBsAg loss and retreatment at 0, 6, 12, 18-21 mos were
5%, 10%, 20%, 29% and 0%, 23%, 25%, 27%, respectively.
Subsequent HBsAg loss was associated with lower baseline
HBsAg [HR/100 IU/L: 0.74 (0.59-0.92), p=0.008] or baseline
HBsAg<100 IU/L [HR:20.6 (5.04-84.3), p<0.001], lower HBsAg
at month 1 [HR/100 IU/L:0.76 (0.62-0.94), p=0.011], higher ALT
at month 1 [HR/10 IU/L: 1.12 (1.01-1.26), p=0.033] and higher
IP10 at month 1 [HR/10 pg/mL: 1.09 (1.01-1.19), p=0.021],
but not with HBcrAg levels. Retreatment was independently
associated with severe pretreatment fibrosis [HR:4.21 (1.45-
12.32), p=0.009] and higher HBcrAg levels [HR=1.86 (1.11-
3.11), p=0.018] or HBcrAg ≥2 log U/mL at ETV/TDF cessation
[HR=3.64 (1.23-10.75), p=0.019]. Median HBcrAg levels were
significantly higher at 1 month before retreatment compared
to all other time points (3.4 vs <2 log U/mL, p<0.001) offering
high accuracy for prediction of retreatment (AUROC: 0.852,
p<0.001). Conclusion: Of CHBe- patients stopping effective
long-term ETV/TDF therapy, >25% may achieve HBsAg loss
and <30% may require retreatment over 18 mos. HBsAg
loss is mainly associated with lower HBsAg levels at therapy
discontinuation, while the probability of retreatment is
associated with the severity of pretreatment fibrosis as well
as with serum HBcrAg levels at ETV/TDF discontinuation and
more importantly at 1 month before retreatment. |
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发表于 2018-10-16 08:41