Korean J Hepatol.  2008 Mar;14(1):58-66. 10.3350/kjhep.2008.14.1.58.

Factors affecting initial virologic response and emergence of resistant mutants after adefovir treatment in lamivudine-resistant chronic hepatitis B patients

• Cho JH
• Cheong JY
• Kang JK
• Park JS
• Lee MH
• Lim NK
• Hong SP
• Kim SO
• Yoo WD
• Cho SW

• KMID: 1073330
• DOI: http://doi.org/10.3350/kjhep.2008.14.1.58

Abstract

BACKGROUND/AIMS: Adefovir dipivoxil (adefovir) effectively inhibits both wild-type and lamivudine-resistant hepatitis B virus (HBV) replication. The development of adefovir resistance is both delayed and infrequent compared with lamivudine resistance. The aim of this study was to characterize the serologic, biochemical, and virologic response to adefovir, and to explore the factors affecting initial virologic response (IVR, defined as a decrease in serum HBV below 4 log10copies/mL after 6 month of treatment) and adefovir resistance in lamivudine resistant HBV-infected patients. METHODS: This study population comprised 76 patients with lamivudine-resistance who had received adefovir for more than 12 months between March 2004 and December 2006. The adefovir-resistant mutant was assayed at 6 months and 12 months during adefovir administration. Restriction-fragment mass polymorphism analysis was used for detecting YMDD and adefovir mutants. RESULTS: After adefovir administration, an IVR was observed in 31% of the patients with lamivudine resistance. Factors associated with an IVR were HBeAg negativity (P=0.04) and the presence of liver cirrhosis (P=0.04). Age, sex, pretreatment levels of alanine aminotransferase and aspartate aminotransferase, pretreatment HBV DNA levels, presence of precore mutation, and type of YMDD mutants were not related to an IVR during adefovir treatment. The prevalence of adefovir resistance was 5% and 13% at 6 months and 12 months after therapy, respectively. Mixed infection of the precore mutant was a risk factors for the emergence of adefovir resistance (P=0.01). CONCLUSIONS: Lamivudine-resistant HBV patients exhibiting HBeAg negativity and liver cirrhosis were more likely to achieve an IVR after adefovir therapy. Adefovir resistance was associated with mixed infection of the precore mutant.

Keyword

Adefovir; Hepatitis B; Lamivudine; Drug resistance

MeSH Terms

Adenine/*analogs & derivatives/therapeutic use
Adult
Alanine Transaminase/blood
Antiviral Agents/*therapeutic use
Aspartate Aminotransferases/blood
DNA, Viral/blood
Drug Resistance, Viral/genetics
Female
Hepatitis B e Antigens/metabolism
Hepatitis B virus/genetics
Hepatitis B, Chronic/*drug therapy/virology
Humans
Lamivudine/*therapeutic use
Male
Middle Aged
Mutation
Phosphonic Acids/*therapeutic use
Polymorphism, Restriction Fragment Length