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P0649
CHARACTERIZATION OF HBsAg LOSS IN PATIENTS WITH CHRONIC
HEPATITIS B (CHB) TREATED WITH NUCLEOS/TIDE ANALOGS
(NUCS): A RETROSPECTIVE MULTICENTER STUDY (HEBESAS)
E. Sua´ rez1, M.A. Simo´ n2, M. Buti3, M. Prieto4, J.M. Pascasio5,
M. Rodr´ıguez6, T. Casanovas7, J. Crespo8, J. Arenas9, R. G´omez10,
B. Figueruela1, M. Diago11, R. Morillas12, J.M. Zozaya13, J.L. Calleja14,
M. Casado15, E. Molina16, J. Fuentes17. 1Gastroenterology,
Hospital Valme, Sevilla, 2Hepatology, Hospital Cl´ınico Lozano Blesa,
Zaragoza, 3Hepatology, Hospital Vall d’Hebr´on-CIBERehd, Barcelona,
4Hepatology, Hopsital La Fe-CIBERehd, Valencia, 5Gastroenterology,
Hospital Virgen del Roc´ıo, Sevilla, 6Hepatology, Hospital Central
de Asturias, Oviedo, 7Hepatology, Hospital Bellvitge, L’Hospitalet,
8Gastroenterology, Hospital Valdecilla, Santander, 9Gastroenterology,
Hospital Donostia, San sebasti´an, 10Gastroenterology, Hospital
Virgen de la Salud, Toledo, 11Hepatology, Cl´ınica Quir´on-Universidad
Cat´olica de Valencia, Valencia, 12Hepatology, Hospital Germans Tr´ıas i
Pujol, Badalona, 13Gastroenterology, Hospital de Navarra, Pamplona,
14Gastroenterology, Hospital Puerta de Hierro-CIBERehd, Madrid,
15Gastroenterology, Hospital Torrec´ardenas, Almer´ıa, 16Hepatology,
Hospital Complex, Santiago de Compostela, 17Hepatology, Hospital
Miguel Servet, Zaragoza, Spain
E-mail: [email protected]
Background and Aims: HBsAg loss is the optimal goal of CHB
treatment but it is difficult to achieve in patients treated with NUCs,
mainly in HBeAg negative patients. The aim of this study was to
investigate the patient characteristics associated with HBsAg loss.
Methods: Retrospective multicenter study of CHB patients treated
with NUCs that lost HBsAg after 2007. Exclusion criteria were
spontaneous or occurred during IFN/PEG-IFN therapy HBsAg
loss, HCV, HDV or HIV coinfection, liver transplantation or HBV
reactivation due to immunosuppressive therapies.
Results: A total of 86 patients were included, 91% male and 94%
Caucasian, median age of 51 years at the time of HBsAg loss. 53%
(45/85) were HBeAg positive at the start of NUCs. Genotype was
available in 32 patients, the majority being D (44%) and A (34%).
Severe fibrosis or cirrhosis was present in 31% (15/49).
HBVDNA was persistently undetectable in 69% patients before
HBsAg loss: median duration 1.19 yr in HBeAg positive and 2.97 yr
in HBeAg negative patients (p = 0.014). Upon HBsAg loss, HBVDNA
was detectable (52 IU/ml) only in one patient and 34% (25/73) had
developed antiHBs. The time between diagnosis of CHB and HBsAg
loss was significantly longer in HBeAg negative than in HBeAg
positive patients: median, 10.5 vs. 3.1 yr, respectively (p < 0.0001).
Although the time from NUCs initiation to HBsAg loss differed
between HBeAg negative and HBeAg positive patients (median,
3.2 vs. 1.9 yr, respectively), it did not reach statistical significance
(p = 0.086).
HBsAg loss occurred in 62.8% patients treated with TDF (39.5%)
or ETV (23.3%), followed by LAM (15.1%) and ADV (9.3%). The
mean time from NUCs initiation to HBsAg loss was 1.8 yr with
ETV/TDF and 6.2 yr with ADV/LAM (difference was 4.4 yr, CI:
3.5–5.3, p < 0.0001) [Box plot].
Treatment was discontinued in 75.6% patients after HBsAg loss
(median, 8.7 months). HBVDNA was undetectable in all patients
and 59% (36/61) had developed antiHBs at the time of NUCs
discontinuation. No HBsAg seroreversion occurred during a median
of 12 months follow-up (range, 2–55 months). No patient developed
hepatic complications or hepatocellular carcinoma.
Conclusions: These data suggest the time between the diagnosis
of CHB and HBsAg loss is longer in HBeAg negative than in HBeAg
positive patients. In addition, HBsAg loss occurred faster with
TDF/ETV than with LAM/ADV. HBsAg loss was maintained in all
patients after discontinuation of NUCs.
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