Effect of Initial Virologic Response to Adefovir on the Development of Resistance to Adefovir in Lamivudine-resistant Chronic Hepatitis B.
10.3350/kjhep.2007.13.3.349
- Author:
In Hee KIM
1
;
Seong Hun KIM
;
Hyun Chul KIM
;
Kyoung Deok SHIN
;
Sang Wook KIM
;
Seung Ok LEE
;
Soo Teik LEE
;
Dae Ghon KIM
Author Information
1. Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Korea. daeghon@chonbuk.ac.kr
- Publication Type:Original Article ; English Abstract
- Keywords:
Adefovir;
Drug resistance;
Hepatitis B, chronic;
Lamivudine
- MeSH:
Adenine/*analogs & derivatives/therapeutic use;
Adult;
Alanine Transaminase/blood;
Antiviral Agents/*therapeutic use;
DNA, Viral/blood;
Drug Resistance, Viral;
Female;
Hepatitis B e Antigens/blood;
Hepatitis B virus/drug effects/genetics;
Hepatitis B, Chronic/*drug therapy/virology;
Humans;
Lamivudine/*therapeutic use;
Male;
Middle Aged;
Phosphonic Acids/*therapeutic use;
Predictive Value of Tests;
Retrospective Studies
- From:The Korean Journal of Hepatology
2007;13(3):349-362
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND/AIMS: Adefovir dipivoxil (ADV) resistance in patients with lamivudine-resistant chronic hepatitis B is not well understood. This study examined the initial virologic response (IVR) to ADV, the rate of ADV resistance and the factors associated with ADV resistance. METHODS: Eighty one lamivudine-resistant HBeAg-positive patients were enrolled in this study. IVR was defined as HBV DNA < 4 log10 copies/mL after 6 months of therapy. RESULTS: IVR was observed in 37/81(45.7%) patients and it was associated with higher pretreatment ALT (P=0.002), and low pretreatment HBV DNA level (P=0.015). The HBV DNA levels were significantly higher in the non-IVR patients than the IVR patients at 12, 18 and 24 months (4.73 vs 2.59, 4.53 vs 2.31, 4.39 vs 2.40 log10 copies/mL, respectively; P<0.01). During the follow-up period, 17(21.0%) patients showed phenotypic resistance to ADV and 9 (11.1%) patients had ADV-resistant mutations. The cumulative probabilities of the phenotypic resistance to ADV at 12 and 24 months were 8.7% and 32.5%, respectively. The cumulative probabilities of the genotypic resistance to ADV at 12 and 24 months were 0% and 14.6%, respectively. Resistance to ADV was associated with a higher pretreatment HBV DNA (P=0.019), and non-IVR (P<0.001). CONCLUSIONS: The cumulative probabilities of the phenotypic and genotypic resistance to ADV at 24 months were 32.5% and 14.6%. The high pretreatment HBV DNA and non-IVR (HBV DNA > or = 4 log10 copies/mL after 6 months of therapy) were associated with ADV resistance.
