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405
Switching to Peginterferon for Chronic
Hepatitis B Patients with Hepatitis B e Antigen
Seroconversion on Entecavir – a Prospective
Study
Henry Lik Yuen Chan1, Fiona Wai Sze Chan2, Aric Josun Hui3,
Michael Kin Kong Li4, Kam Hon Chan5, Grace Lai Hung Wong6,
Ching Kong Loo2, Angel Mei Ling Chim6, Chi Hang Tse7 and
Vincent Wai Sun Wong7, (1)Institute of Digestive Disease,
Department of Medicine and Therapeutics, and State Key
Laboratory of Digestive Disease, The Chinese University of
Hong Kong, Hong Kong, (2)Kwong Wah Hospital, (3)Alice
Ho Miu Ling Nethersole Hospital, (4)Tuen Mun Hospital,
(5)North District Hospital, (6)Department of Medicine and
Therapeutics, The Chinese University of Hong Kong, (7)The
Chinese University of Hong Kong
Background: Nucleos(t)ide analogues (NA) are effective
in suppressing hepatitis B virus (HBV) replication, but most
patients require long-term treatment. Previous studies have
reported approximately 9%-10% hepatitis B surface antigen
(HBsAg) loss among HBeAg-negative patients on entecavir
shifted to 1 year of peginterferon. With this background,
we hypothesized that patients who developed HBeAg
seroconversion on NA would benefit from immune modulation
by peginterferon treatment. This study evaluated the efficacy
and safety of switching to peginterferon among patients who
had HBeAg seroconversion on NA treatment. Methods: This
is a prospective, multi-center, single-arm, open-label study
(NCT 02068365). HBeAg-positive chronic hepatitis B patients
who developed HBeAg seroconversion during NA treatment
were studied. All patients received open-label peginterferon
alfa-2a 180mcg/week for 48 weeks, and NA was stopped
at week 4 of peginterferon treatment. Primary endpoint was
sustained response, which was defined as negative HBeAg,
positive anti-HBe and HBV DNA <2000 IU/ml at week 72.
Other secondary endpoints including HBsAg loss at week
72 were also studied. Results: Forty-one patients treated
by entecavir for 56±23 months were recruited. Sustained
response was achieved in 30 patients (73%, 95% confidence
interval 58%-84%). At week 72, 31 (76%) patients had HBeAg
seroconversion, 23 (56%) patients had undetectable HBV
DNA, 31 (76%) patients had normal ALT, and 6 patients (15%)
had HBsAg loss. Three patients had entecavir restarted at
week 68-72 due to elevated HBV DNA (143,004 to 637,860
IU/ml) with ALT of 36-67 U/l, and they were regarded as
treatment failure at week 72. On logistic regression analysis,
lower HBsAg level at baseline was the strongest predictor
of sustained response [odds ratio 0.12 (95% CI 0.02-0.77)]
and HBsAg loss [odds ratio of 0.08 (95% CI 0.01-0.62) ]. By
receiver operating characteristic (ROC) curve analysis, the
best HBsAg cutoff for sustained response was <1500 IU/ml
[area under ROC curve 0.75 (95% CI 0.58-0.92)] and that
for HBsAg loss was <500 IU/ml [area under ROC curve 0.88
(95% CI 0.75-1.00)]. Twenty-two of 25 (88%) patients with
baseline HBsAg <1500 IU/ml had sustained response. Five of
10 (50%) patients with baseline HBsAg <500 IU/ml developed
HBsAg loss. Five patients have laboratory abnormalities
requiring dose reduction of peginterferon. Peginterferon was
generally safe with no serious adverse event related to the
study drug. Conclusion: Switching to peginterferon can be
considered as a treatment option in NA-treated patients with
HBeAg seroconversion. The rate of HBsAg loss is high (15%),
and it can be up to 50% among those with HBsAg levels <500
IU/ml.
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发表于 2018-10-16 08:36
