title: α-fetoprotein levels after interferon therapy and risk of hepatocarcinogenesis in chronic hepatitis C.
abstract: The effects of interferon (IFN) treatment and the post-IFN treatment α-fetoprotein (AFP) levels on risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC) are unknown. To determine the relationship between AFP and alanine transaminase (ALT) levels and HCC risk, a cohort consisting of 1,818 patients histologically proven to have CHC treated with IFN were studied. Cumulative incidence and HCC risk were analyzed over a mean follow-up period of 6.1 years using the Kaplan-Meier method and Cox proportional hazard analysis. HCC developed in 179 study subjects. According to multivariate analysis, older age, male gender, advanced fibrosis, severe steatosis, lower serum albumin levels, non sustained virological response (non-SVR), and higher post-IFN treatment ALT or AFP levels were identified as independent factors significantly associated with HCC development. Cutoff values for ALT and AFP for prediction of future HCC were determined as 40 IU/L and 6.0 ng/mL, respectively, and negative predictive values of these cutoffs were high at 0.960 in each value. The cumulative incidence of HCC was significantly lower in patients whose post-IFN treatment ALT and AFP levels were suppressed to less than the cutoff values even in non-SVR patients. This suppressive effect was also found in patients whose post-IFN treatment ALT and AFP levels were reduced to less than the cutoff values despite abnormal pretreatment levels.
  
  
  CONCLUSIONS
  Post-IFN treatment ALT and AFP levels are significantly associated with hepatocarcinogenesis. Measurement of these values is useful for predicting future HCC risk after IFN treatment. Suppression of these values after IFN therapy reduces HCC risk even in patients without HCV eradication.
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan; Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan; Department of Liver Disease Control, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Asahina
authors.forename: Kaoru
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishimura
authors.forename: Masaru
authors.initials: M
authors.lastname: Muraoka
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Nobuharu
authors.initials: N
authors.lastname: Tamaki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yasui
authors.forename: Takanori
authors.initials: T
authors.lastname: Hosokawa
authors.forename: Ken
authors.initials: K
authors.lastname: Ueda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakanishi
authors.forename: Jun
authors.initials: J
authors.lastname: Itakura
authors.forename: Yuka
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kurosaki
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Enomoto
authors.forename: Mina
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Sei
authors.initials: S
authors.lastname: Kakinuma
authors.forename: Mamoru
authors.initials: M
authors.lastname: Watanabe
authors.forename: Namiki
authors.initials: N
authors.lastname: Izumi
mesh_terms: D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology*; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D019698:Hepatitis C, Chronic / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000453:epidemiology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D000509:alpha-Fetoproteins / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D000509:alpha-Fetoproteins; D007372:Interferons; D000410:Alanine Transaminase