[Clinical and virologic characteristics of lamivudine resistance in HBV-associated chronic liver disease].
OBJECTIVE
Lamivudine therapy in chronic hepatitis B has been shown to be effective in inhibiting HBV replication. However, lamivudine resistance has been developed with prolonged use. We studied to determine the prevalence, predictive factors, and clinical outcomes of lamivudine resistance. Mutations in YMDD motif of HBV polymerase, which have been associated with lamivudine resistance, were also assessed.


METHODS
170 patients with HBV-associated chronic liver disease who have received lamivudine for at least one year, were studied. The clinical, biochemical, and virologic characteristics were analyzed and compared according to presence (resistance group) or absence (non-resistance group) of DNA breakthrough. Their clinical outcomes were regularly followed. Stored sera before treatment and after DNA breakthrough were examined for detection of HBV polymerase mutation by direct sequencing and/or RFLP.


RESULTS
Cumulative rates of lamivudine resistance after one and two years of treatment were 11% and 34%, respectively. In the resistance group, as compared to the non-resistance group, age, the presence of HBeAg before treatment, and disappearance of HBeAg during treatment, were significantly different. The predictive factors associated with lamivudine resistance were not found. ALT and HBV-DNA level after lamivudine resistance was variable, but jaundice or hepatic failure was absent. Mutation in YMDD motif was detected in 73% and other variable mutations were detected before treatment and after DNA breakthrough.


CONCLUSIONS
Lamivudine resistance increases the longer the duration of treatment and clinical outcomes are variable. The mutation in YMDD motif was found in about 2/3 of cases. Other causes for lamivudine resistance may be considered.
Kim
Sun Suk
SS
Department of Internal Medicine, Gachon Medical School, Gil Medical Center, Inchon, Korea. ssk@ghil.com
Chung
Moon Gi
MG
Ju
Ki Tak
KT
Park
Dong Kyun
DK
Kwon
Oh Sang
OS
Koo
Yang Suh
YS
Kim
Yu Kyung
YK
Choi
Duck Ju
DJ
Hwang
Yu Jin
YJ
Kim
Ju Hyun
JH
D000328:Adult; D020816:Amino Acid Motifs / Q000235:genetics; D000998:Antiviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D006515:Hepatitis B virus / Q000187:drug effects*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation
D000998:Antiviral Agents; D019259:Lamivudine