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Conference Paper: Profound reduction of HBV covalently closed circular DNA with long-term nucleoside/tide analogue therapy

TitleProfound reduction of HBV covalently closed circular DNA with long-term nucleoside/tide analogue therapy
Authors
KeywordsMedical sciences
Gastroenterology
Issue Date2014
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/
Citation
The 65th Annual Meeting of the American Association for the Study of Liver Diseases (The Liver Meeting 2014 - AASLD), Boston, MA., 7-11 November 2014. In Hepatology, 2014, v. 60 suppl. S1, p. 1090A, abstract no. 1855 How to Cite?
AbstractBACKGROUND: Long-term nucleoside/tide analogue (NA) treatment suppresses serum HBV DNA to undetectable levels in a majority of patients. We aimed to investigate the effect of longterm NA on the suppression of covalently closed circular DNA (cccDNA) and intrahepatic HBV DNA (ihHBV-DNA). METHODS: We recruited 40 patients (median age 44.2 years, range 24.3-63.2) who had been on continuous long-term (5 – 10 years) NA. All patients had 3 liver biopsies: at baseline, after 1 year of treatment and at the last follow-up. Serum HBV DNA and HBsAg were measured by the COBAS TaqMan HBV Test and the Elecsys HBsAg II Assay, respectively (both Roche Diagnostics). ihHBV-DNA and cccDNA were assayed by real-time PCR, with lower limits of detection of 0.001 and 0.005 copies/cell, respectively. RESULTS: The median duration of treatment was 10.5 years (range: 6.0 – 11.9 years). At baseline, 13 patients had 100mg lamivudine, 11 had 600mg telbivudine, 9 had 0.5mg entecavir, 4 had 30mg clevudine, and 3 had 10mg adefovir. At the last follow up, these patients were on 0.5-1.0mg entecavir (n=23), 600mg telbivudine (n=9), 10mg adefovir (n=4), 300mg tenofovir (n=2), or combination therapy of lamivudine plus adefovir/tenofovir (n=2). Histology of the third biopsy showed complete resolution of interface hepatitis in 60% of patients with the remainder showing mild-to-moderate activity. Persistent immunoreactivity for HBsAg was found in 80%, the mean number of hepatocytes positive for HBsAg being 10.4% (range 1-80%). All but 1 (2.5%) was immunoreactive for HBcAg. At baseline, the median serum HBV DNA, HBsAg, ihHBV-DNA and cccDNA levels were 6.84 logIU/mL, 3.38 logIU/mL, 286 copies/cell, and 7.3 copies/cell, respectively. At the time of the last biopsies, 36 (90%) patients had undetectable serum HBV DNA (<20 IU/mL), all but one patient still had detectable HBsAg (median: 2.74 logIU/mL), all had detectable ihHBV-DNA (median: 0.4 copies/cell), but 18 (45%) patients had undetectable cccDNA. There was a trend of reduction of HBsAg, ihHBV-DNA and cccDNA levels from baseline to 1 year to last follow-up (all p<0.0001). The median log drop of HBsAg at last biopsy was 0.55 logIU/mL. The median percentage reductions of HBsAg, ihHBV-DNA and cccDNA at last biopsies were 71.46%, 99.85% and 99.89%, respectively. CONCLUSIONS: Long-term NA treatment significantly reduced cccDNA and ihDNA. 45% of patients had undetectable cccDNA, although small amount of ihHBV-DNA were still detectable in all patients. Integrated HBV DNA may be a possible source of detectable ihHBV-DNA and HBsAg. Continuous long-term NA therapy can reduce cccDNA to undetectable levels, suggesting a possible end-point of treatment.
DescriptionPoster Session 4: Hepatitis B Therapy: no. 1855 / This free journal suppl. entitled: Special Issue: The 65th Annual Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting 2014
Persistent Identifierhttp://hdl.handle.net/10722/211480
ISSN
2015 Impact Factor: 11.711
2015 SCImago Journal Rankings: 4.752

 

DC FieldValueLanguage
dc.contributor.authorLai, CL-
dc.contributor.authorWong, DKH-
dc.contributor.authorIp, P-
dc.contributor.authorKopaniszen, M-
dc.contributor.authorSeto, WK-
dc.contributor.authorFung, J-
dc.contributor.authorHuang, FY-
dc.contributor.authorLee, BP-
dc.contributor.authorCullaro, G-
dc.contributor.authorWu, CH-
dc.contributor.authorCheng, C-
dc.contributor.authorYuen, JCH-
dc.contributor.authorNgai, V-
dc.contributor.authorYuen, MF-
dc.date.accessioned2015-07-15T06:21:17Z-
dc.date.available2015-07-15T06:21:17Z-
dc.date.issued2014-
dc.identifier.citationThe 65th Annual Meeting of the American Association for the Study of Liver Diseases (The Liver Meeting 2014 - AASLD), Boston, MA., 7-11 November 2014. In Hepatology, 2014, v. 60 suppl. S1, p. 1090A, abstract no. 1855-
dc.identifier.issn0270-9139-
dc.identifier.urihttp://hdl.handle.net/10722/211480-
dc.descriptionPoster Session 4: Hepatitis B Therapy: no. 1855 / This free journal suppl. entitled: Special Issue: The 65th Annual Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting 2014-
dc.description.abstractBACKGROUND: Long-term nucleoside/tide analogue (NA) treatment suppresses serum HBV DNA to undetectable levels in a majority of patients. We aimed to investigate the effect of longterm NA on the suppression of covalently closed circular DNA (cccDNA) and intrahepatic HBV DNA (ihHBV-DNA). METHODS: We recruited 40 patients (median age 44.2 years, range 24.3-63.2) who had been on continuous long-term (5 – 10 years) NA. All patients had 3 liver biopsies: at baseline, after 1 year of treatment and at the last follow-up. Serum HBV DNA and HBsAg were measured by the COBAS TaqMan HBV Test and the Elecsys HBsAg II Assay, respectively (both Roche Diagnostics). ihHBV-DNA and cccDNA were assayed by real-time PCR, with lower limits of detection of 0.001 and 0.005 copies/cell, respectively. RESULTS: The median duration of treatment was 10.5 years (range: 6.0 – 11.9 years). At baseline, 13 patients had 100mg lamivudine, 11 had 600mg telbivudine, 9 had 0.5mg entecavir, 4 had 30mg clevudine, and 3 had 10mg adefovir. At the last follow up, these patients were on 0.5-1.0mg entecavir (n=23), 600mg telbivudine (n=9), 10mg adefovir (n=4), 300mg tenofovir (n=2), or combination therapy of lamivudine plus adefovir/tenofovir (n=2). Histology of the third biopsy showed complete resolution of interface hepatitis in 60% of patients with the remainder showing mild-to-moderate activity. Persistent immunoreactivity for HBsAg was found in 80%, the mean number of hepatocytes positive for HBsAg being 10.4% (range 1-80%). All but 1 (2.5%) was immunoreactive for HBcAg. At baseline, the median serum HBV DNA, HBsAg, ihHBV-DNA and cccDNA levels were 6.84 logIU/mL, 3.38 logIU/mL, 286 copies/cell, and 7.3 copies/cell, respectively. At the time of the last biopsies, 36 (90%) patients had undetectable serum HBV DNA (<20 IU/mL), all but one patient still had detectable HBsAg (median: 2.74 logIU/mL), all had detectable ihHBV-DNA (median: 0.4 copies/cell), but 18 (45%) patients had undetectable cccDNA. There was a trend of reduction of HBsAg, ihHBV-DNA and cccDNA levels from baseline to 1 year to last follow-up (all p<0.0001). The median log drop of HBsAg at last biopsy was 0.55 logIU/mL. The median percentage reductions of HBsAg, ihHBV-DNA and cccDNA at last biopsies were 71.46%, 99.85% and 99.89%, respectively. CONCLUSIONS: Long-term NA treatment significantly reduced cccDNA and ihDNA. 45% of patients had undetectable cccDNA, although small amount of ihHBV-DNA were still detectable in all patients. Integrated HBV DNA may be a possible source of detectable ihHBV-DNA and HBsAg. Continuous long-term NA therapy can reduce cccDNA to undetectable levels, suggesting a possible end-point of treatment.-
dc.languageeng-
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/-
dc.relation.ispartofHepatology-
dc.rightsHepatology. Copyright © John Wiley & Sons, Inc.-
dc.subjectMedical sciences-
dc.subjectGastroenterology-
dc.titleProfound reduction of HBV covalently closed circular DNA with long-term nucleoside/tide analogue therapy-
dc.typeConference_Paper-
dc.identifier.emailLai, CL: hrmelcl@hkucc.hku.hk-
dc.identifier.emailWong, DKH: danywong@hku.hk-
dc.identifier.emailIp, P: philipip@hku.hk-
dc.identifier.emailKopaniszen, M: malkop@hku.hk-
dc.identifier.emailSeto, WK: wkseto2@hku.hk-
dc.identifier.emailFung, J: jfung@hkucc.hku.hk-
dc.identifier.emailHuang, FY: fungyu@hkucc.hku.hk-
dc.identifier.emailWu, CH: rchwu@hku.hk-
dc.identifier.emailYuen, JCH: jchyuen@hkucc.hku.hk-
dc.identifier.emailYuen, MF: mfyuen@hku.hk-
dc.identifier.authorityLai, CL=rp00314-
dc.identifier.authorityWong, DKH=rp00492-
dc.identifier.authorityIp, P=rp01890-
dc.identifier.authoritySeto, WK=rp01659-
dc.identifier.authorityFung, J=rp00518-
dc.identifier.authorityYuen, MF=rp00479-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1002/hep.27532-
dc.identifier.hkuros244913-
dc.identifier.hkuros244926-
dc.identifier.volume60-
dc.identifier.issuesuppl. S1-
dc.identifier.spage1090A, abstract no. 1855-
dc.identifier.epage1090A, abstract no. 1855-
dc.publisher.placeUnited States-

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