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Conference Paper: Predictive value of HBV DNA levels at frequent time points during early and maintenance phase of 5-year laminudine and mutational profiles of reverse transcriptase (RT) and surface (S) genes

TitlePredictive value of HBV DNA levels at frequent time points during early and maintenance phase of 5-year laminudine and mutational profiles of reverse transcriptase (RT) and surface (S) genes
Authors
Issue Date2006
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/
Citation
Hepatology, 2006, v. 44 suppl. S1, p. 557A, abstract no. 991 How to Cite?
AbstractBACKGROUND: The optimal time points and levels of HBV DNA during initial therapy with lamivudine (LAM) to predict the 5-year outcome are unknown. AIMS: To identify 1) the optimal time and HBV DNA levels during early treatment phase associated with good response (GR) (HBV DNA level 2000 copies/mL); 2) the mutational profiles after 5-year LAM treatment. PATIENTS AND METHODS: HBV DNA levels at baseline, week (wk) 0,2,4,8,16,24,32 and yearly till 5 years were measured by VERSANT® HBV DNA 3.0 assay (Bayer HealthCare LLC, NY) in 74 Chinese chronic hepatitis B patients on continuous LAM treatment. Determination of parts of the nucleotide sequence of RT and S genes by TRUGENE® HBV Genotyping Kit (Bayer HealthCare LLC) were completed in 50 patients. RESULTS: 20 (27%) patients had GR at year 5. Table shows the percentages of patients achieving GR at 5 years according to the cut-off HBV DNA levels of 4 logs at different early time points. Compared to patients with HBV DNA levels still 4 logs at wk 12, patients with HBV DNA level 4 logs had significantly higher rate of HBeAg seroconversion (20.3 vs. 90%, p0.001), ALT normalization (51.5% vs. 100%, p 0.008) and lower chance of YMDD mutations (62.8% vs. 0%, p 0.002) at year 5. The corresponding figures as assessed at wk 24 are 18.6% vs. 73.3%, p 0.001; 48.3% vs. 92.3%, p 0.007; 62.5% vs. 20%, p 0.03 respectively. The sensitivity and specificity of using this cut-off level for determination of GR at 5 years are 50% and 100% for wk 12, and 60% and 96.2% for wk 24. Mutations of YMDD motif with M204I/V were associated with L180M and V173L (both p0.05). Because of the overlapping of RT and S genes, corresponding S mutations with E164D (with V173L), I195M (with M204I), W196L/M/S/V/X (with M204V)(all p0.05) were observed. These S mutants decrease the anti-HBs binding affinity (Torresi et al., 2002). 2 patients had the vaccine escape S mutation G145R/A at baseline, while 6 developed this mutation during LAM treatment. CONCLUSIONS: HBV DNA level 4 logs copies/mL at wk 12 during LAM treatment had excellent predictive value for long-term outcome. GR only occurred in 15.6% of patients who failed to achieve this target. Only 4.5% of patients with HBV DNA levels 4 logs at wk 48 achieved GR at year 5. Potential impact of RT mutations associated with S mutations affecting anti-HBs binding affinity should be addressed. Week
Persistent Identifierhttp://hdl.handle.net/10722/102362
ISSN
2015 Impact Factor: 11.711
2015 SCImago Journal Rankings: 4.752

 

DC FieldValueLanguage
dc.contributor.authorYuen, RMFen_HK
dc.contributor.authorWong, DKHen_HK
dc.contributor.authorFung, JYYen_HK
dc.contributor.authorYuen, JCHen_HK
dc.contributor.authorLai, CLen_HK
dc.date.accessioned2010-09-25T20:27:35Z-
dc.date.available2010-09-25T20:27:35Z-
dc.date.issued2006en_HK
dc.identifier.citationHepatology, 2006, v. 44 suppl. S1, p. 557A, abstract no. 991en_HK
dc.identifier.issn0270-9139en_HK
dc.identifier.urihttp://hdl.handle.net/10722/102362-
dc.description.abstractBACKGROUND: The optimal time points and levels of HBV DNA during initial therapy with lamivudine (LAM) to predict the 5-year outcome are unknown. AIMS: To identify 1) the optimal time and HBV DNA levels during early treatment phase associated with good response (GR) (HBV DNA level 2000 copies/mL); 2) the mutational profiles after 5-year LAM treatment. PATIENTS AND METHODS: HBV DNA levels at baseline, week (wk) 0,2,4,8,16,24,32 and yearly till 5 years were measured by VERSANT® HBV DNA 3.0 assay (Bayer HealthCare LLC, NY) in 74 Chinese chronic hepatitis B patients on continuous LAM treatment. Determination of parts of the nucleotide sequence of RT and S genes by TRUGENE® HBV Genotyping Kit (Bayer HealthCare LLC) were completed in 50 patients. RESULTS: 20 (27%) patients had GR at year 5. Table shows the percentages of patients achieving GR at 5 years according to the cut-off HBV DNA levels of 4 logs at different early time points. Compared to patients with HBV DNA levels still 4 logs at wk 12, patients with HBV DNA level 4 logs had significantly higher rate of HBeAg seroconversion (20.3 vs. 90%, p0.001), ALT normalization (51.5% vs. 100%, p 0.008) and lower chance of YMDD mutations (62.8% vs. 0%, p 0.002) at year 5. The corresponding figures as assessed at wk 24 are 18.6% vs. 73.3%, p 0.001; 48.3% vs. 92.3%, p 0.007; 62.5% vs. 20%, p 0.03 respectively. The sensitivity and specificity of using this cut-off level for determination of GR at 5 years are 50% and 100% for wk 12, and 60% and 96.2% for wk 24. Mutations of YMDD motif with M204I/V were associated with L180M and V173L (both p0.05). Because of the overlapping of RT and S genes, corresponding S mutations with E164D (with V173L), I195M (with M204I), W196L/M/S/V/X (with M204V)(all p0.05) were observed. These S mutants decrease the anti-HBs binding affinity (Torresi et al., 2002). 2 patients had the vaccine escape S mutation G145R/A at baseline, while 6 developed this mutation during LAM treatment. CONCLUSIONS: HBV DNA level 4 logs copies/mL at wk 12 during LAM treatment had excellent predictive value for long-term outcome. GR only occurred in 15.6% of patients who failed to achieve this target. Only 4.5% of patients with HBV DNA levels 4 logs at wk 48 achieved GR at year 5. Potential impact of RT mutations associated with S mutations affecting anti-HBs binding affinity should be addressed. Week-
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.rightsHepatology . Copyright © John Wiley & Sons, Inc.en_HK
dc.titlePredictive value of HBV DNA levels at frequent time points during early and maintenance phase of 5-year laminudine and mutational profiles of reverse transcriptase (RT) and surface (S) genesen_HK
dc.typeConference_Paperen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0270-9139&volume=44&issue=4 suppl 1&spage=991&epage=&date=2006&atitle=Predictive+value+of+HBV+DNA+levels+at+frequent+time+points+during+early+and+maintenance+phase+of+5-year+laminudine+and+mutational+profiles+of+reverse+transcriptase+(RT)+and+surface+(S)+genesen_HK
dc.identifier.emailYuen, RMF: mfyuen@hkucc.hku.hken_HK
dc.identifier.emailWong, DKH: danywong@hku.hken_HK
dc.identifier.emailFung, JYY: jfung@sicklehut.comen_HK
dc.identifier.emailYuen, JCH: jchyuen@HKUCC.hku.hken_HK
dc.identifier.emailLai, CL: hrmelcl@hku.hken_HK
dc.identifier.authorityYuen, RMF=rp00479en_HK
dc.identifier.authorityWong, DKH=rp00492en_HK
dc.identifier.authorityFung, JYY=rp00518en_HK
dc.identifier.authorityLai, CL=rp00314en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1002/hep.21398-
dc.identifier.hkuros130892en_HK
dc.identifier.volume44en_HK
dc.identifier.issuesuppl. S1en_HK
dc.identifier.spage557A, abstract no. 991en_HK
dc.identifier.epage557A, abstract no. 991-

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