Lamivudine-to-entecavir switching treatment in type B chronic hepatitis patients without evidence of lamivudine resistance.
OBJECTIVE
A considerable number of chronic hepatitis B (CH-B) patients remain under continuous lamivudine treatment, although switching treatment to entecavir could be beneficial. We investigated the antiviral efficacy of switching treatment to entecavir in CH-B patients without apparent evidence of lamivudine resistance during the preceding lamivudine treatment.


METHODS
Forty-four CH-B patients, who underwent lamivudine treatment for more than 6 months and showed no evidence of lamivudine resistance, switched to entecavir. Serial changes in hepatitis B virus (HBV) DNA were correlated with the patients' baseline HBV DNA at the commencement of entecavir administration. The entecavir-resistant substitution was examined by PCR-direct sequencing. The median follow-up period of entecavir treatment was 20 (10-23) months.


RESULTS
All 31 patients with baseline HBV DNA <2.6 logcopies/ml maintained HBV DNA-negative status during entecavir treatment. Of seven patients having HBV DNA of 2.6-<4.0 logcopies/ml, all achieved undetectable HBV DNA at the end of follow-up. As for six patients having HBV DNA >or=4.0 logcopies/ml, three patients achieved undetectable HBV DNA, whereas virological breakthrough was observed in one patient at month 15. An entecavir-resistant virus having rtM204V, rtL180M and rtS202G substitutions was detected in this patient.


CONCLUSIONS
The lamivudine-to-entecavir switching treatment may be generally recommendable in CH-B patients without evidence of lamivudine resistance during the preceding lamivudine treatment. However, great care should be taken with respect to the emergence of entecavir-resistance, especially in patients who do not respond well to the preceding lamivudine treatment.
Kurashige
Nao
N
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
Ohkawa
Kazuyoshi
K
Hiramatsu
Naoki
N
Yakushijin
Takayuki
T
Mochizuki
Kiyoshi
K
Oze
Tsugiko
T
Kiso
Shinichi
S
Kanto
Tatsuya
T
Takehara
Tetsuo
T
Kasahara
Akinori
A
Doi
Yoshinori
Y
Yamada
Akira
A
Fukuda
Kazuto
K
Oshita
Masahide
M
Mita
Eiji
E
Fukui
Hiroyuki
H
Nagase
Toshihiko
T
Yoshihara
Harumasa
H
Imai
Yasuharu
Y
Kato
Michio
M
Kashihara
Takeshi
T
Hayashi
Norio
N
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral; D005260:Female; D005500:Follow-Up Studies; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006515:Hepatitis B virus / Q000187:drug effects; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D000998:Antiviral Agents; D004279:DNA, Viral; D019259:Lamivudine; C413685:entecavir; D006147:Guanine