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Article: Profound suppression of hepatitis B virus replication with lamivudine

TitleProfound suppression of hepatitis B virus replication with lamivudine
Authors
Issue Date2000
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/32763
Citation
Journal Of Medical Virology, 2000, v. 61 n. 3, p. 367-373 How to Cite?
AbstractThe therapeutic goals in chronic hepatitis B are to prevent or decrease cirrhosis and hepatocellular carcinoma in patients with pre-cirrhotic or early cirrhotic disease and to stabilise patients with end-stage cirrhosis. Lamivudine is an oral nucleoside analogue that suppresses hepatitis B virus (HBV) replication, and so may achieve both these treatment objectives. The active 5'-triphosphate metabolite of lamivudine has two modes of viral suppression. First, it mimics deoxycytidine triphosphate and is incorporated into newly synthesised HBV DNA to cause chain termination. Second, it demonstrates competitive inhibition of viral DNA-dependent and RNA-dependent DNA polymerase activity (i.e., reverse transcriptase activity). Lamivudine may, therefore, act at four possible stages during HBV replication: reverse transcription of pre-genomic mRNA into nascent minus-strand DNA; formation of plus strand DNA from nascent minus-strand DNA; completion of double-stranded DNA; and formation of covalently closed circular DNA. In clinical studies, lamivudine therapy reduced serum HBV DNA and this was associated with significant improvements in liver histology and significant and sustained enhancement of the proliferative CD4-mediated response to HBeAg and hepatitis B core antigen (HBcAg), and an increased frequency of HBeAg-specific T cells. HBV DNA concentrations often returned to pre-treatment values when therapy ended prior to the loss of hepatitis B e antigen (HBeAg). Although the emergence of HBV variants with a mutation in the YMDD (tyrosine-methionine- aspartate-aspartate) motif has been observed, such variants show reduced susceptibility to lamivudine due to limited replication competence, and their emergence is not a signal to cease lamivudine therapy. In conclusion, viral suppression with lamivudine offers a means of disease improvement and immunological control in chronic hepatitis B. (C) 2000 Wiley-Liss. Inc.
Persistent Identifierhttp://hdl.handle.net/10722/77171
ISSN
2015 Impact Factor: 1.998
2015 SCImago Journal Rankings: 1.015
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLai, CLen_HK
dc.contributor.authorYuen, MFen_HK
dc.date.accessioned2010-09-06T07:29:02Z-
dc.date.available2010-09-06T07:29:02Z-
dc.date.issued2000en_HK
dc.identifier.citationJournal Of Medical Virology, 2000, v. 61 n. 3, p. 367-373en_HK
dc.identifier.issn0146-6615en_HK
dc.identifier.urihttp://hdl.handle.net/10722/77171-
dc.description.abstractThe therapeutic goals in chronic hepatitis B are to prevent or decrease cirrhosis and hepatocellular carcinoma in patients with pre-cirrhotic or early cirrhotic disease and to stabilise patients with end-stage cirrhosis. Lamivudine is an oral nucleoside analogue that suppresses hepatitis B virus (HBV) replication, and so may achieve both these treatment objectives. The active 5'-triphosphate metabolite of lamivudine has two modes of viral suppression. First, it mimics deoxycytidine triphosphate and is incorporated into newly synthesised HBV DNA to cause chain termination. Second, it demonstrates competitive inhibition of viral DNA-dependent and RNA-dependent DNA polymerase activity (i.e., reverse transcriptase activity). Lamivudine may, therefore, act at four possible stages during HBV replication: reverse transcription of pre-genomic mRNA into nascent minus-strand DNA; formation of plus strand DNA from nascent minus-strand DNA; completion of double-stranded DNA; and formation of covalently closed circular DNA. In clinical studies, lamivudine therapy reduced serum HBV DNA and this was associated with significant improvements in liver histology and significant and sustained enhancement of the proliferative CD4-mediated response to HBeAg and hepatitis B core antigen (HBcAg), and an increased frequency of HBeAg-specific T cells. HBV DNA concentrations often returned to pre-treatment values when therapy ended prior to the loss of hepatitis B e antigen (HBeAg). Although the emergence of HBV variants with a mutation in the YMDD (tyrosine-methionine- aspartate-aspartate) motif has been observed, such variants show reduced susceptibility to lamivudine due to limited replication competence, and their emergence is not a signal to cease lamivudine therapy. In conclusion, viral suppression with lamivudine offers a means of disease improvement and immunological control in chronic hepatitis B. (C) 2000 Wiley-Liss. Inc.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/32763en_HK
dc.relation.ispartofJournal of Medical Virologyen_HK
dc.rightsJournal of Medical Virology. Copyright © John Wiley & Sons, Inc.en_HK
dc.subject.meshAntiviral Agents - pharmacology - therapeutic useen_HK
dc.subject.meshHepatitis B virus - drug effects - physiologyen_HK
dc.subject.meshHepatitis B, Chronic - drug therapy - virologyen_HK
dc.subject.meshHumansen_HK
dc.subject.meshLamivudine - pharmacology - therapeutic useen_HK
dc.subject.meshVirus Replication - drug effectsen_HK
dc.titleProfound suppression of hepatitis B virus replication with lamivudineen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0146-6615&volume=61&issue=3&spage=367&epage=373&date=2000&atitle=Profound+suppression+of+hepatitis+B+virus+replication+with+lamivudineen_HK
dc.identifier.emailLai, CL:hrmelcl@hku.hken_HK
dc.identifier.emailYuen, MF:mfyuen@hkucc.hku.hken_HK
dc.identifier.authorityLai, CL=rp00314en_HK
dc.identifier.authorityYuen, MF=rp00479en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/1096-9071(200007)61:3<367::AID-JMV15>3.0.CO;2-Aen_HK
dc.identifier.pmid10861648-
dc.identifier.scopuseid_2-s2.0-0000590610en_HK
dc.identifier.hkuros59909en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0000590610&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume61en_HK
dc.identifier.issue3en_HK
dc.identifier.spage367en_HK
dc.identifier.epage373en_HK
dc.identifier.isiWOS:000087395300015-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLai, CL=7403086396en_HK
dc.identifier.scopusauthoridYuen, MF=7102031955en_HK

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