1858
On-treatment alpha-fetoprotein levels have a strong association with hepatocellular carcinoma development among chronic hepatitis B patients receiving entecavir
Ryoko Yamada1, Naoki Hiramatsu1, Yuki Tahata1, Naoki Mor-ishita1, Naoki Harada1, Tsugiko Oze1, Takayuki Yakushijin1, Sadaharu Iio2, Yoshinori Doi3, Eiji Mita4, Masahide Oshita5, Toshifumi Ito6, Taizo Hijioka7, Kazuhiro Katayama8, Shinji Tamura9, Harumasa Yoshihara10, Yasuharu Imai11, Takuya Miy-agi1, Yuichi Yoshida1, Tomohide Tatsumi1, Norio Hayashi12, Tet-suo Takehara1;
1Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan; 2Higashiosaka City Central Hospital, Higashiosaka, Japan; 3Ote-mae Hospital, Osaka, Japan; 4National Hospital Organization Osaka National Hospital, Osaka, Japan; 5Osaka Police Hospital, Osaka, Japan; 6Japan Community Health care Organization Osaka Hospital, Osaka, Japan; 7National Hospital Organization Osaka Minami Medical Center, Kawachinagano, Japan; 8Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan; 9Minoh City Hospital, Minoh, Japan; 10Osaka Rosai Hospital, Sakai, Japan; 11Ikeda Municipal Hospital, Ikeda, Japan; 12Kansai Rosai Hospital, Amagasaki, Japan
Entecavir (ETV) is one of the first-line nucleoside analogues (NA) for patients with chronic hepatitis B virus (HBV) infection. However, risk factors for hepatocellular carcinoma (HCC) during ETV treatment remain unclear. We investigated risk factors for HCC among pre-treatment factors and on-treatment factors in patients with chronic HBV infection undergoing ETV treatment. A total of 496 NA-naïve patients without history of HCC at baseline or HCC development within one year of ETV treatment were enrolled in this study. The baseline characteristics were as follows: age, 52.6 ± 12.0 years old; males, 58%; positive for HB e antigen, 45%; cirrhosis, 19 %and median HBV DNA, 6.9 log copies/mL (LC/mL). The mean treatment duration was 49.9 ± 17.5 months. Achievement rates of HBV DNA negativity (< 2.6 LC/mL) and ALT normalization (< 30 IU/L) at 24 weeks after initiation of ETV treatment were 68 %and 62%, respectively. The median serum AFP level decreased significantly from 5.7 (ng/mL) at baseline to 4.0 at 24 weeks (p < 0.001) (non-cirrhosis, from 5.0 to 4.0, p < 0.001; cirrhosis, from 10.0 to 6.0, p < 0.001). HCC occurred in 42 patients. The cumulative incidence of HCC at 3, 5 and 7 years was 6.0%, 9.6 %and 17.2 %among all enrolled patients. In a multivariate analysis, advanced age (≥ 55 years) (hazard ratio (HR), 2.84; p = 0.018), cirrhosis (HR, 5.59; p < 0.001) at baseline, and the higher AFP level (> 10 ng/mL) at 24 weeks (HR, 2.38; p = 0.034) were independently associated with HCC incidence. HCC incidence was not associated with HBV DNA negativity or ALT normalization at 24 weeks (p = 0.685, p = 0.076). The risk analysis for HCC incidence adjusted with three risk factors, the AFP level at 24 weeks, age and cirrhosis at baseline was performed. When the AFP level remained high (≥ 10 ng/mL) at 24 weeks, the cumulative incidence of HCC at 5 years were 7.2 %with no other risk factors, 18.0 %with the factor of age ≥ 55 years at baseline, 33.1 %with the factor of cirrhosis at baseline, and 65.4 %with factors of age ≥ 55 years and cirrhosis at baseline. The AFP level at 24 weeks after initiation of ETV treatment seemed not to be the marker indicating the existence of HCC, but to be the representative marker of a potential for HCC development because the AFP level among patients who developed HCC had not increased from 24 weeks (13.2 ± 22.4 ng/mL) to 48 weeks (10.2 ± 17.8 ng/mL) after the initiation of ETV treatment. In conclusion, in the consecutive surveillance for HCC after the initiation of ETV treatment, monitoring the change of the AFP level at 24 weeks is important, especially among patients with advanced age or cirrhosis.