Impact of alpha-fetoprotein on hepatocellular carcinoma development during entecavir treatment of chronic hepatitis B virus infection.
BACKGROUND
Entecavir (ETV) is one of the first-line nucleoside analogs for treating patients with chronic hepatitis B virus (HBV) infection. However, the hepatocellular carcinoma (HCC) risk for ETV-treated patients remains unclear.


METHODS
A total of 496 Japanese patients with chronic HBV infection undergoing ETV treatment were enrolled in this study. The baseline characteristics were as follows: age 52.6 ± 12.0 years, males 58%, positive for hepatitis B e antigen 45 %, cirrhosis 19%, and median HBV DNA level 6.9 log copies (LC) per milliliter. The mean treatment duration was 49.9 ± 17.5 months.


RESULTS
The proportions of HBV DNA negativity (below 2.6 LC/mL) were 68% at 24 weeks and 86% at 1 year, and the rates of alanine aminotransferase (ALT) level normalization were 62 and 72%, respectively. The mean serum alpha-fetoprotein (AFP) levels decreased significantly at 24 weeks after ETV treatment initiation (from 29.0 ± 137.1 to 5.7 ± 27.9 ng/mL, p < 0.001). The cumulative incidence of HCC at 3, 5, and 7 years was 6.0, 9.6, and 17.2%, respectively, among all enrolled patients. In a multivariate analysis, advanced age [55 years or older, hazard ratio (HR) 2.84; p = 0.018], cirrhosis (HR 5.59, p < 0.001), and a higher AFP level (10 ng/mL or greater) at 24 weeks (HR 2.38, p = 0.034) were independent risk factors for HCC incidence. HCC incidence was not affected by HBV DNA negativity or by ALT level normalization at 24 weeks.


CONCLUSIONS
The AFP level at 24 weeks after ETV treatment initiation can be the on-treatment predictive factor for HCC incidence among patients with chronic HBV infection.
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Ryoko
R
Yamada
Naoki
N
Hiramatsu
Tsugiko
T
Oze
Naoki
N
Morishita
Naoki
N
Harada
Takayuki
T
Yakushijin
Sadaharu
S
Iio
Yoshinori
Y
Doi
Akira
A
Yamada
Akira
A
Kaneko
Hideki
H
Hagiwara
Eiji
E
Mita
Masahide
M
Oshita
Toshifumi
T
Itoh
Hiroyuki
H
Fukui
Taizo
T
Hijioka
Kazuhiro
K
Katayama
Shinji
S
Tamura
Harumasa
H
Yoshihara
Yasuharu
Y
Imai
Michio
M
Kato
Takuya
T
Miyagi
Yuichi
Y
Yoshida
Tomohide
T
Tatsumi
Akinori
A
Kasahara
Toshimitsu
T
Hamasaki
Norio
N
Hayashi
Tetsuo
T
Takehara
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000453:epidemiology / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008113:Liver Neoplasms / Q000097:blood* / Q000453:epidemiology / Q000209:etiology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult; D000509:alpha-Fetoproteins / Q000378:metabolism*
D000998:Antiviral Agents; D014408:Biomarkers, Tumor; D000509:alpha-Fetoproteins; C413685:entecavir; D006147:Guanine