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发表于 2003-11-23 18:28
The American Journal of Gastroenterology
Volume 98 , Issue 11 , Pages 2505-2515
[B]Treatment of chronic hepatitis B virus infection via oral immune regulation
toward hepatitis B virus proteins[/B]
Rifaat Safadi a , Eran Israeli a , Orit Papo b , Oren Shibolet a , Alaa
Melhem a , Aharon Bloch a , Mina Rowe a , Ruslana Alper a , Athalia Klein a
, Nilla Hemed a , Ori Segol c , Barbara Thalenfeld c , Dean Engelhardt d ,
Elazar Rabbani d and Yaron Ilan a *
Received: 12/30/2002. Accepted: 4/4/2003.
Abstract
Objectives
Hepatitis B virus (HBV) is a noncytopathic virus, and hepatocellular injury
is mediated by a defective host antiviral immune response. We have
previously shown that antiviral immunity can be modulated through oral
feeding of viral proteins. The aims of this study were to determine the
safety and efficacy of treatment of patients with chronic HBV by means of
p.o. administration of HBV envelope proteins.
Methods
A total of 42 chronic HBV patients were treated p.o. with HBV envelope
proteins (HBsAg+preS1+preS2), three times/wk for 20-30 wk, and followed for
an additional 20 wk. Patients were monitored for HBV-DNA levels, liver
enzymes, and liver histology. HBV-directed T cell immune modulation was
assessed in vitro by HBV specific T cell-proliferation, cytotoxicity, IFN?,
and IL10 ELISPOT assays, and reverse transcription-polymerase chain reaction
cytokines assay.
Results
Favorable response in one of the primary endpoints was achieved in 28/42
patients (66.6%) by means of p.o. immune regulation. A significant decrease
in viral load was observed in 15 patients (35.7%). HBsAg/HBcAg biopsy scores
improved in 41% and 57.1% of patients, respectively. Histological
improvement in liver necroinflammatory score was noted in 12/40 patients
(30%). In all, 80% showed biochemical response. Five of 19 HBeAg positive
patients (26.3%) became negative for HBeAg. A favorable augmentation in
anti-HBV specific T cell response, with increased HbsAg specific T cell
proliferation (78%), cytotoxicity (75%), and IFN? positive T cell clones
(62.9%) was noted. In addition, a decrease in the IL10 ? positive T cell
clones was achieved (48.1%). Natural killer T (NKT) lymphocytes increased
significantly in all treated patients.
Conclusions
Immune regulation of the anti-HBV immune response via p.o. administration of
HBV envelope proteins alleviated the immune-mediated liver injury while
augmenting the effective antiviral immunity.
--------------------------------------------------------------------------------
Affiliations:
a Liver Unit, Department of Medicine, Hadassah-Hebrew University Medical
Center, Jerusalem, Israel. b Department of Pathology, Hadassah-Hebrew
University Medical Center, Jerusalem, Israel. c Emek Medical Center, Afula,
Israel. d ENZO Biochem, New York, New York, USA.
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