Long-term effect of lamivudine treatment on the incidence of hepatocellular carcinoma in patients with hepatitis B virus infection.
BACKGROUND
Nucleotide analogues have recently been approved for the treatment of patients with hepatitis B virus (HBV) infection. However, it is still controversial whether the decrease of HBV-DNA amount induced by treatment with nucleotide analogues can reduce the risk of hepatocellular carcinoma (HCC) development in HBV patients.


METHODS
A total of 293 HBV patients without HCC who were treated with lamivudine (LAM) were enrolled in a multicenter trial. The incidence of HCC was examined after the start of LAM therapy, and the risk factors for liver carcinogenesis were analyzed. The mean follow-up period was 67.6 ± 27.4 months.


RESULTS
On multivariate analysis for HCC development in all patients, age ≥50 years, platelet count <14.0 × 10(4)/mm(3), cirrhosis, and median HBV-DNA levels of ≥4.0 log copies/ml during LAM treatment were significant risk factors. The cumulative carcinogenesis rate at 5 years was 3% in patients with chronic hepatitis and 30% in those with cirrhosis. For the chronic hepatitis patients, the log-rank test showed the significant risk factors related to HCC development to be age ≥50 years, platelet count <14.0 × 10(4)/mm(3), and hepatitis B e antigen negativity, but median HBV-DNA levels of <4.0 log copies/ml (maintained viral response, MVR) did not significantly suppress the development of HCC. In cirrhosis patients, however, the attainment of MVR during LAM treatment was revealed to reduce the risk of HCC development.


CONCLUSIONS
These results suggest that the incidence of HCC in HBV patients with cirrhosis can be reduced in those with an MVR induced by consecutive LAM treatment.
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Mika
M
Kurokawa
Naoki
N
Hiramatsu
Tsugiko
T
Oze
Takayuki
T
Yakushijin
Masanori
M
Miyazaki
Atsushi
A
Hosui
Takuya
T
Miyagi
Yuichi
Y
Yoshida
Hisashi
H
Ishida
Tomohide
T
Tatsumi
Shinichi
S
Kiso
Tatsuya
T
Kanto
Akinori
A
Kasahara
Sadaharu
S
Iio
Yoshinori
Y
Doi
Akira
A
Yamada
Masahide
M
Oshita
Akira
A
Kaneko
Kiyoshi
K
Mochizuki
Hideki
H
Hagiwara
Eiji
E
Mita
Toshifumi
T
Ito
Yoshiaki
Y
Inui
Kazuhiro
K
Katayama
Harumasa
H
Yoshihara
Yasuharu
Y
Imai
Eijirou
E
Hayashi
Norio
N
Hayashi
Tetsuo
T
Takehara
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006515:Hepatitis B virus / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D019259:Lamivudine / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D004279:DNA, Viral; D019259:Lamivudine