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Conference Paper: Role of regulatory T cells in natural immunity and sustained pharmacological control of chronic hepatitis B infection

TitleRole of regulatory T cells in natural immunity and sustained pharmacological control of chronic hepatitis B infection
Authors
Issue Date2006
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/
Citation
The 57th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), Boston, USA, 27-31 October 2006. In Hepatology, 2006, v. 44 n. 4 Suppl. 1, p. 543A, abstract no. 956 How to Cite?
AbstractBackground/Aim: The effectiveness of hepatitis B virus therapy is reflected not only by the reduction of viral load but also recovery of viral-specific T-cell immunity. Regulatory T cells (Treg) can suppress the functions of CD4 and CD8 effector cells. The aim of the current study is to investigate the role of Treg in nucleoside/ nucleotide analogue (Nucs)-induced and spontaneous sustained Background/Aim: The effectiveness of hepatitis B virus therapy is reflected not only by the reduction of viral load but also recovery of viral-specific T-cell immunity. Regulatory T cells (Treg) can suppress the functions of CD4 and CD8 effector cells. The aim of the current study is to investigate the role of Treg in nucleoside/ nucleotide analogue (Nucs)-induced and spontaneous sustained remission after HBeAg-seroconversion. Methods: We studied 30 hepatitis B e antigen (HBeAg)-positive patients treated with either adefovir dipivoxil (ADV) monotherapy [n 16] or ADV in combination with emtricitabine [n 14] for 96 weeks followed by ADV monotherapy. Nucs was discontinued 6-months after HBeAgseroconversion and patients followed-up for post-treatment relapse (HBV DNA 10,000 copies/ml with ALT 2 times upper limit of normal). Nine historical control patients with spontaneous HBeAg-seroconversion were recruited for comparison. Serial HBV DNA, Treg (defined as CD4 CD25 CD45RO CTLA-4 ) cell frequency by FACS, FoxP3 mRNA expression level by realtime PCR and intracellular cytokine staining for virus-specific CD8 T-cells by FACS were evaluated every 4-8 weekly. Results: At the time of analysis, 10 of 30 patients (33.3%) had HBeAgseroconversion. All these 10 patients had normal serum ALT and HBV DNA 300 copies/ml at the end-of-treatment (ET). After follow-up of mean 16.1 months, 4 of the 10 patients (40.0%) with Nucs-induced HBeAg-seroconversion had sustained response (SR)and 6 patients (60.0%) had post-treatment relapse. A decline in Treg (mean /- SEM 1.89 /- 0.47 vs. 4.35 /- 1.02 respectively, p 0.01) and FoxP3 (mean /- SEM 14.62 /- 7.48 vs. 48.89 /-24.51 respectively, p 0.002) was detected 8-weeks before HBeAgseroconversion in patients with spontaneous HBeAg-seroconversion when compared with baseline. This decrease in Treg and FoxP3 was sustained until 24 weeks after spontaneous HBeAgseroconversion. No change in Treg was detected in Nucs-induced HBeAg-seroconversion. The 4 patients with SR showed a significantly lower percentage of Treg at ET (mean /- SEM 1.50 /-0.63) when compared with the 6 patients with post-treatment relapse (mean /- SEM 4.41 /- 1.34, p 0.03). Post-treatment relapse was preceded by an increase in Treg and FoxP3. Downregulation of Treg was associated with an increase in virus-specific CD8 T-cells. However, no serum ALT flare was detected during T cell recovery. Conclusion: Downregulation of Treg is associated with spontaneous HBeAg seroconversion and sustained post-treatment remission without cytolytic mediated liver damage. A lower Treg at ET contribute to SR upon withdrawal of nucs after HBeAg-seroconversion.
Persistent Identifierhttp://hdl.handle.net/10722/107622
ISSN
2015 Impact Factor: 11.711
2015 SCImago Journal Rankings: 4.752

 

DC FieldValueLanguage
dc.contributor.authorHui, CKen_HK
dc.contributor.authorZhang, HYen_HK
dc.contributor.authorLee, PYen_HK
dc.contributor.authorMommeja-Marin, Hen_HK
dc.contributor.authorYueng, YHen_HK
dc.contributor.authorLeung, KWen_HK
dc.contributor.authorLu, Len_HK
dc.contributor.authorLeung, Nen_HK
dc.contributor.authorLuk, JMCen_HK
dc.contributor.authorNaoumov, NNen_HK
dc.contributor.authorHuang, FPen_HK
dc.contributor.authorLau, Gen_HK
dc.date.accessioned2010-09-26T00:05:26Z-
dc.date.available2010-09-26T00:05:26Z-
dc.date.issued2006en_HK
dc.identifier.citationThe 57th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), Boston, USA, 27-31 October 2006. In Hepatology, 2006, v. 44 n. 4 Suppl. 1, p. 543A, abstract no. 956en_HK
dc.identifier.issn0270-9139en_HK
dc.identifier.urihttp://hdl.handle.net/10722/107622-
dc.description.abstractBackground/Aim: The effectiveness of hepatitis B virus therapy is reflected not only by the reduction of viral load but also recovery of viral-specific T-cell immunity. Regulatory T cells (Treg) can suppress the functions of CD4 and CD8 effector cells. The aim of the current study is to investigate the role of Treg in nucleoside/ nucleotide analogue (Nucs)-induced and spontaneous sustained Background/Aim: The effectiveness of hepatitis B virus therapy is reflected not only by the reduction of viral load but also recovery of viral-specific T-cell immunity. Regulatory T cells (Treg) can suppress the functions of CD4 and CD8 effector cells. The aim of the current study is to investigate the role of Treg in nucleoside/ nucleotide analogue (Nucs)-induced and spontaneous sustained remission after HBeAg-seroconversion. Methods: We studied 30 hepatitis B e antigen (HBeAg)-positive patients treated with either adefovir dipivoxil (ADV) monotherapy [n 16] or ADV in combination with emtricitabine [n 14] for 96 weeks followed by ADV monotherapy. Nucs was discontinued 6-months after HBeAgseroconversion and patients followed-up for post-treatment relapse (HBV DNA 10,000 copies/ml with ALT 2 times upper limit of normal). Nine historical control patients with spontaneous HBeAg-seroconversion were recruited for comparison. Serial HBV DNA, Treg (defined as CD4 CD25 CD45RO CTLA-4 ) cell frequency by FACS, FoxP3 mRNA expression level by realtime PCR and intracellular cytokine staining for virus-specific CD8 T-cells by FACS were evaluated every 4-8 weekly. Results: At the time of analysis, 10 of 30 patients (33.3%) had HBeAgseroconversion. All these 10 patients had normal serum ALT and HBV DNA 300 copies/ml at the end-of-treatment (ET). After follow-up of mean 16.1 months, 4 of the 10 patients (40.0%) with Nucs-induced HBeAg-seroconversion had sustained response (SR)and 6 patients (60.0%) had post-treatment relapse. A decline in Treg (mean /- SEM 1.89 /- 0.47 vs. 4.35 /- 1.02 respectively, p 0.01) and FoxP3 (mean /- SEM 14.62 /- 7.48 vs. 48.89 /-24.51 respectively, p 0.002) was detected 8-weeks before HBeAgseroconversion in patients with spontaneous HBeAg-seroconversion when compared with baseline. This decrease in Treg and FoxP3 was sustained until 24 weeks after spontaneous HBeAgseroconversion. No change in Treg was detected in Nucs-induced HBeAg-seroconversion. The 4 patients with SR showed a significantly lower percentage of Treg at ET (mean /- SEM 1.50 /-0.63) when compared with the 6 patients with post-treatment relapse (mean /- SEM 4.41 /- 1.34, p 0.03). Post-treatment relapse was preceded by an increase in Treg and FoxP3. Downregulation of Treg was associated with an increase in virus-specific CD8 T-cells. However, no serum ALT flare was detected during T cell recovery. Conclusion: Downregulation of Treg is associated with spontaneous HBeAg seroconversion and sustained post-treatment remission without cytolytic mediated liver damage. A lower Treg at ET contribute to SR upon withdrawal of nucs after HBeAg-seroconversion.-
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/en_HK
dc.relation.ispartofHepatologyen_HK
dc.relation.ispartofHepatology-
dc.rightsHepatology. Copyright © John Wiley & Sons, Inc.en_HK
dc.titleRole of regulatory T cells in natural immunity and sustained pharmacological control of chronic hepatitis B infectionen_HK
dc.typeConference_Paperen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0270-9139&volume=44&issue=4&spage=543A&epage=543A&date=2006&atitle=Role+of+regulatory+T+cells+in+natural+immunity+and+sustained+pharmacological+control+of+chronic+hepatitis+B+infectionen_HK
dc.identifier.emailHui, CK: ckh23@cam.ac.uken_HK
dc.identifier.emailLee, PY: nikkilee@hkucc.hku.hken_HK
dc.identifier.emailYueng, YH: yhyueng@HKUCC-COM.hku.hken_HK
dc.identifier.emailLeung, KW: leungkan@graduate.hku.hken_HK
dc.identifier.emailLu, L: lulei427@gmail.comen_HK
dc.identifier.emailLuk, JMC: jmluk@hkucc.hku.hken_HK
dc.identifier.emailLau, G: gkklau@netvigator.comen_HK
dc.identifier.authorityLuk, JMC=rp00349en_HK
dc.identifier.doi10.1002/hep.21398-
dc.identifier.hkuros137291en_HK
dc.identifier.volume44en_HK
dc.identifier.issue4, Suppl. 1en_HK
dc.identifier.spage543en_HK
dc.identifier.epage543en_HK

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