title: Post-treatment levels of α-fetoprotein predict incidence of hepatocellular carcinoma after interferon therapy.
abstract: OBJECTIVE
  In patients with chronic hepatitis C virus (HCV) infection, lack of sustained virologic response (SVR) 24 weeks after the end of interferon therapy is a significant risk factor for hepatocellular carcinoma (HCC). Although many pretreatment factors are known to affect HCC incidence, less is known about post-treatment factors-many change during the course of interferon therapy.
  
  
  METHODS
  We performed a prospective study, collecting data from 2659 patients with chronic hepatitis C without a history of HCC who had been treated with pegylated interferon (Peg-IFN) plus ribavirin from 2002 through 2008 at hospitals in Japan. Biopsy specimens were collected before treatment; all patients received Peg-IFN plus ribavirin for 48 to 72 weeks (HCV genotype 1) or 24 weeks (HCV genotype 2). Hematologic, biochemical, and virologic data were collected every 4 weeks during treatment and every 6 months after treatment. HCC was diagnosed based on angiography, computed tomography, and/or magnetic resonance imaging findings.
  
  
  RESULTS
  HCC developed in 104 patients during a mean observation period of 40 months. Older age, male sex, lower platelet counts and higher levels of α-fetoprotein at baseline, and lack of an SVR were significant risk factors for HCC. The cumulative incidence of HCC was significantly lower in patients without SVRs who relapsed than those with no response to treatment. Levels of α-fetoprotein 24 weeks after the end of treatment (AFP24) were significantly lower than levels of α-fetoprotein at baseline in patients with SVRs and those who relapsed, but not in nonresponders. Post-treatment risk factors for HCC among patients with SVRs included higher AFP24 level and older age; among those without SVRs, risk factors included higher AFP24 level, integrated level of alanine aminotransferase, older age, and male sex. AFP24 (≥10 ng/mL, 10-5 ng/mL, and then <5 ng/mL) was a better predictor of HCC incidence than pretreatment level of AFP among patients with and without SVRs.
  
  
  CONCLUSIONS
  In patients with chronic HCV infection, levels of α-fetoprotein decrease during interferon therapy. High post-treatment levels of α-fetoprotein predict HCC, regardless of whether patients achieve an SVR. University Hospital Medical Information Network Clinical Trials Registry: C000000196, C000000197.
authors: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Tsugiko
authors: T
authors: Oze
authors: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. Electronic address: hiramatsu@gh.med.osaka-u.ac.jp.
authors: Naoki
authors: N
authors: Hiramatsu
authors: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Takayuki
authors: T
authors: Yakushijin
authors: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Masanori
authors: M
authors: Miyazaki
authors: Sumitomo Hospital, Osaka, Osaka, Japan.
authors: Akira
authors: A
authors: Yamada
authors: Osaka Police Hospital, Osaka, Osaka, Japan.
authors: Masahide
authors: M
authors: Oshita
authors: Kansai Rosai Hospital, Amagasaki, Hyogo, Japan.
authors: Hideki
authors: H
authors: Hagiwara
authors: National Hospital Organization Osaka National Hospital, Osaka, Osaka, Japan.
authors: Eiji
authors: E
authors: Mita
authors: Osaka Koseinenkin Hospital, Osaka, Osaka, Japan.
authors: Toshifumi
authors: T
authors: Ito
authors: Yao Municipal Hospital, Yao, Osaka, Japan.
authors: Hiroyuki
authors: H
authors: Fukui
authors: Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo, Japan.
authors: Yoshiaki
authors: Y
authors: Inui
authors: National Hospital Organization Osaka Minami Medical Center, Kawachinagano, Osaka, Japan.
authors: Taizo
authors: T
authors: Hijioka
authors: Toyonaka Municipal Hospital, Toyonaka, Osaka, Japan.
authors: Masami
authors: M
authors: Inada
authors: Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Osaka, Japan.
authors: Kazuhiro
authors: K
authors: Katayama
authors: Minoh City Hospital, Minoh, Osaka, Japan.
authors: Shinji
authors: S
authors: Tamura
authors: Osaka Rosai Hospital, Sakai, Osaka, Japan.
authors: Harumasa
authors: H
authors: Yoshihara
authors: Osaka General Medical Center, Osaka, Osaka, Japan.
authors: Atsuo
authors: A
authors: Inoue
authors: Ikeda Municipal Hospital, Ikeda, Osaka, Japan.
authors: Yasuharu
authors: Y
authors: Imai
authors: Kinki Central Hospital of Mutual Aid Association of Public School Teachers, Itami, Osaka, Japan.
authors: Eijiro
authors: E
authors: Hayashi
authors: National Hospital Organization Minami Wakayama Medical Center, Tanabe, Wakayama, Japan.
authors: Michio
authors: M
authors: Kato
authors: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Takuya
authors: T
authors: Miyagi
authors: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Yuichi
authors: Y
authors: Yoshida
authors: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Tomohide
authors: T
authors: Tatsumi
authors: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Akinori
authors: A
authors: Kasahara
authors: Department of Biomedical Statistics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Toshimitsu
authors: T
authors: Hamasaki
authors: Kansai Rosai Hospital, Amagasaki, Hyogo, Japan.
authors: Norio
authors: N
authors: Hayashi
authors: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors: Tetsuo
authors: T
authors: Takehara
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology*; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D016898:Interferon-alpha / Q000627:therapeutic use; D007564:Japan / Q000453:epidemiology; D008113:Liver Neoplasms / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D012307:Risk Factors; D000509:alpha-Fetoproteins / Q000032:analysis*
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D000509:alpha-Fetoproteins; D012254:Ribavirin
keywords: ALT; Liver Cancer; Outcome; Response to Therapy; Risk Factor