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KMID : 1103920120180010075
Korean Journal of Hepatology
2012 Volume.18 No. 1 p.75 ~ p.83
High efficacy of adefovir and entecavir combination therapy in patients with nucleoside-refractory hepatitis B
Chae Hee-Bok

Kim Mi-Jin
Seo Eui-Keun
Choi Yong-Hyeok
Lee Hee-Seung
Han Joung-Ho
Yoon Soon-Man
Park Seon-Mee
Youn Sei-Jin
Abstract
Background/Aims: Newly developed and potent antiviral agents suffer from the problem of drug resistance. Multidrug resistance is a major impediment in the treatment of patients with chronic hepatitis B (CHB). In line with American Association for the Study of Liver Diseases guidelines, adefovir dipivoxil (ADV) add-on therapy is recommended in the case of lamivudine resistance, while tenofovir disoproxil fumarate (TDF) is recommended for ADV or entecavir (ETV) resistance. TDF is currently not available in Korea. ADV+ETV combination therapy may be a viable alternative to TDF in patients with either ADV or ETV resistance. However, the efficacy of ADV+ETV combination therapy in patients with CHB and multidrug resistance is unclear. This study investigated the efficacy of ADV+ETV combination therapy in patients with multidrug resistance.

Methods: Twenty-five patients were enrolled and were administered ADV+ETV combination therapy for at least 6 months. Blood was drawn at baseline and at 3, 6, 9, and 12 months after commencing treatment, and the following blood parameters were analyzed: alanine transaminase, hepatitis B e-antigen (HBeAg), anti-hepatitis B e-antigen, and hepatitis B virus (HBV) DNA levels. The initial virological response (IVR) was defined as an HBV DNA level of <4 log10 copies/mL after 6 months of combination therapy.

Results: The IVR rate was 76%. The proportion of patients with a high viral load (¡Ã5.0 log) dropped from 76% at baseline to only 5% after 6 months of treatment. The biochemical response rate during the first 6 months was 71%. HBeAg was lost in 2 patients (10%).

Conclusions: ADV+ETV combination therapy induced a good IVR in CHB patients who were refractory to more than 2 antiviral agents. This regimen may be a good alternative to TDF in Korea, where that drug is not available.
KEYWORD
Adefovir, Entecavir, Combination drug therapy, Drug resistance, Treatment efficacy
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