[Factors affecting initial virologic response and emergence of resistant mutants after adefovir treatment in lamivudine-resistant chronic hepatitis B patients].
OBJECTIVE
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.
Cho
Jin Hee
JH
Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.
Cheong
Jae Youn
JY
Kang
Joon Koo
JK
Park
Jin Sun
JS
Lee
Myoung Hee
MH
Lim
Nam Kyu
NK
Hong
Sun Pyo
SP
Kim
Soo-Ok
SO
Yoo
Wang Don
WD
Cho
Sung Won
SW
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D006513:Hepatitis B e Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000627:therapeutic use*; D012150:Polymorphism, Restriction Fragment Length
D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D019259:Lamivudine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000225:Adenine; C106812:adefovir dipivoxil