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Long-term adefovir dipivoxil monotherapy for up to 5 years in lamivudine-resistant chronic hepatitis B

 Jung Min Lee  ;  Jun Yong Park  ;  Do Young Kim  ;  Tin Nguyen  ;  Sun Pyo Hong  ;  Soo Ok Kim  ;  Chae Yoon Chon  ;  Kwang-Hyub Han  ;  Sang Hoon Ahn 
 ANTIVIRAL THERAPY, Vol.15(2) : 235-241, 2010 
Journal Title
Issue Date
Adenine/administration & dosage ; Adenine/analogs & derivatives* ; Adenine/pharmacology ; Adenine/therapeutic use ; Adult ; Aged ; Antiviral Agents/administration & dosage ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use* ; DNA, Viral/blood ; Drug Resistance, Viral* ; Female ; Hepatitis B e Antigens/blood ; Hepatitis B virus/drug effects* ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/drug therapy* ; Hepatitis B, Chronic/virology ; Humans ; Korea ; Lamivudine/administration & dosage ; Lamivudine/pharmacology* ; Lamivudine/therapeutic use ; Male ; Middle Aged ; Organophosphonates/administration & dosage ; Organophosphonates/pharmacology ; Organophosphonates/therapeutic use* ; Reverse Transcriptase Inhibitors/administration & dosage ; Reverse Transcriptase Inhibitors/pharmacology ; Reverse Transcriptase Inhibitors/therapeutic use* ; Time Factors ; Treatment Outcome ; Young Adult
BACKGROUND: Large clinical studies assessing long-term adefovir dipivoxil salvage monotherapy in patients with lamivudine-resistant chronic hepatitis B (CHB) are lacking, particularly in patients positive for hepatitis B e antigen (HBeAg). We assessed the efficacy and resistance profile of adefovir dipivoxil monotherapy for up to 5 years in a large cohort of Korean patients with lamivudine-resistant CHB. METHODS: A total of 320 patients (81.3% HBeAg-positive; 100% genotype C) with confirmed genotypic lamivudine-resistant CHB were switched to adefovir dipivoxil 10 mg once daily. Liver function tests and HBV DNA were monitored every 3 months. Genotypic resistance to adefovir dipivoxil was performed in patients with detectable HBV DNA. RESULTS: The overall cumulative virological response rate at 5 years of adefovir dipivoxil therapy was 48.8%. The virological response rate was significantly higher in HBeAg-negative patients (62.0% versus 45.9%; P=0.010). Most cases of virological response (131/134, 97.8%) occurred within the first 36 months of therapy. The 5-year cumulative probability of genotypic resistance and virological breakthrough was 65.6% and 61.8%, respectively. Predictive factors for a virological response included baseline HBeAg seronegativity, HBV DNA< or =8 log(10) copies/ml and achievement of an on-treatment initial virological response. CONCLUSIONS: Adefovir dipivoxil salvage monotherapy for lamivudine-resistant CHB resulted in a modest cumulative virological response rate at 5 years, which was associated with progressive antiviral resistance. Consequently, adefovir monotherapy is not preferable as a first-line strategy for lamivudine resistance where combination lamivudine plus adefovir dipivoxil therapy is available.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Do Young(김도영)
Park, Jun Yong(박준용) ORCID logo https://orcid.org/0000-0001-6324-2224
Ahn, Sang Hoon(안상훈) ORCID logo https://orcid.org/0000-0002-3629-4624
Lee, Jung Min(이중민)
Chon, Chae Yoon(전재윤)
Han, Kwang-Hyub(한광협) ORCID logo https://orcid.org/0000-0003-3960-6539
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