Impact of alpha-fetoprotein on hepatocellular carcinoma development during entecavir treatment of chronic hepatitis B virus infection.

Abstract

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.

• Authors: Ryoko Yamada, Naoki Hiramatsu, Tsugiko Oze, Naoki Morishita, Naoki Harada, Takayuki Yakushijin, Sadaharu Iio, Yoshinori Doi, Akira Yamada, Akira Kaneko, Hideki Hagiwara, Eiji Mita, Masahide Oshita, Toshifumi Itoh, Hiroyuki Fukui, Taizo Hijioka, Kazuhiro Katayama, Shinji Tamura, Harumasa Yoshihara, Yasuharu Imai, Michio Kato, Takuya Miyagi, Yuichi Yoshida, Tomohide Tatsumi, Akinori Kasahara, Toshimitsu Hamasaki, Norio Hayashi, Tetsuo Takehara, Osaka Liver Forum
• Journal: Journal of gastroenterology (J Gastroenterol) Vol. 50 Issue 7 Pg. 785-94 (Jul 2015) ISSN: 1435-5922 [Electronic] Japan
• PMID: 25384794 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Biomarkers, Tumor
• alpha-Fetoproteins
• entecavir
• Guanine

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antiviral Agents (therapeutic use)
• Biomarkers, Tumor (blood)
• Carcinoma, Hepatocellular (blood, epidemiology, etiology)
• Female
• Follow-Up Studies
• Guanine (analogs & derivatives, therapeutic use)
• Hepatitis B, Chronic (complications, drug therapy)
• Humans
• Incidence
• Japan (epidemiology)
• Liver Neoplasms (blood, epidemiology, etiology)
• Male
• Middle Aged
• Retrospective Studies
• Risk Factors
• Young Adult
• alpha-Fetoproteins (metabolism)