Efficacy of lamivudine treatment in Japanese patients with hepatitis B virus-related cirrhosis.
BACKGROUND
Several clinical trials have suggested that lamivudine therapy is effective in patients with hepatitis B virus (HBV)-related cirrhosis. However, there are few studies of lamivudine therapy in Japanese patients with HBV cirrhosis. The aim of this study was to evaluate the efficacy of lamivudine therapy in Japanese patients with cirrhosis, and to evaluate the clinical course after the emergence of YMDD mutants.


METHODS
Fifty-four consecutive adult Japanese patients with HBV-related cirrhosis were enrolled and continuously treated with lamivudine, daily for 6-35 months (median, 25 months). Twelve of the 54 patients were hepatitis B envelope antigen (HBeAg)-positive. The clinical courses of 21 of the patients were evaluated using the Child-Pugh-Turcott (CPT) score.


RESULTS
Lamivudine suppressed serum HBV-DNA to undetectable levels (<3.7 LGE/ml) in 77.8% of patients at 12 months and in 61.3% at 24 months. Before the emergence of YMDD mutants, clinical improvement, defined as a decrease in the CPT score of 2 points or more, was apparent in 6 of 21 (29%) patients. No change in CPT score was evident in 14 of 21 patients (67%). YMDD mutants emerged in 19 of 54 (35%) patients. The cumulative emergence rates increased each year. The emergence rate of YMDD mutants in patients with HBV cirrhosis was higher than that in patients with chronic hepatitis. After the emergence of YMDD mutants, 3 of 12 (25%) patients with YMDD mutants showed CPT score increases of 2 points or more.


CONCLUSIONS
Lamivudine therapy improved the clinical course in some cirrhotic patients. However, in patients with Child's B and C cirrhosis, the emergence of YMDD mutants sometimes led to deterioration of liver function.
Ooga
Hiromi
H
Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, 105-8470, Tokyo, Japan.
Suzuki
Fumitaka
F
Tsubota
Akihito
A
Arase
Yasuji
Y
Suzuki
Yoshiyuki
Y
Akuta
Norio
N
Sezaki
Hitomi
H
Hosaka
Tetsuya
T
Someya
Takashi
T
Kobayashi
Masahiro
M
Saitoh
Satoshi
S
Ikeda
Kenji
K
Kobayashi
Mariko
M
Matsuda
Marie
M
Satoh
Junko
J
Kumada
Hiromitsu
H
D005260:Female; D006509:Hepatitis B / Q000150:complications*; D006513:Hepatitis B e Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D013997:Time Factors
D006513:Hepatitis B e Antigens; D019259:Lamivudine