title: Long-term follow-up of interferon monotherapy in 454 consecutive naive patients infected with hepatitis C virus: multi-course interferon therapy may reduce the risk of hepatocellular carcinoma and increase survival.
abstract: OBJECTIVE
  The long-term effects of multi-course interferon (IFN) monotherapy in patients infected with hepatitis C virus (HCV) are still unclear.
  
  
  METHODS
  To evaluate the effects of multi-course IFN on hepatocarcinogenesis and survival, a follow-up study was conducted comprising 454 consecutively recruited non-cirrhotic naive patients infected with HCV, who had received IFN monotherapy between 1987 and 1992. The median follow-up was 11.3 years.
  
  
  RESULTS
  A sustained response (SR) after the first IFN was achieved by 152 patients (33.5%) (Group A). Of 302 patients (66.5%) with non-SR after the first IFN, 130 patients (28.6%) did not receive additional IFN (Group B), and the remaining 172 patients (37.9%) received multi-course IFN monotherapy (Group C). With regard to hepatocarcinogenesis and survival rates for liver-related deaths, Groups A and C both showed significantly better long-term clinical outcome than Group B (p < 0.001; log-rank test). Three independent factors were identified by multivariate analyses (fibrosis stage 3, Group B, and age > or = 50) for all patients and two factors (fibrosis stage 3 and age > or = 50) for Group C associated with hepatocarcinogenesis. With regard to hepatocarcinogenesis rates according to the mean alanine aminotransferase (ALAT) levels during the IFN-free period in Group C, significantly higher rates were noted in patients with ALAT levels above 1.5 x the upper normal limit (17.6%) than those below the limit (0%) (p < 0.05).
  
  
  CONCLUSIONS
  Multi-course IFN monotherapy reduces the risk of hepatocarcinogenesis and increases survival, and low ALAT levels during the IFN-free period are associated with lower hepatocarcinogenesis rates in multi-course IFN.
authors.affiliation: Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan. akuta-gi@umin.ac.jp
authors.forename: Norio
authors.initials: N
authors.lastname: Akuta
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Suzuki
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Hitomi
authors.initials: H
authors.lastname: Sezaki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hosaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Someya
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Saitoh
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Arase
authors.forename: Kenji
authors.initials: K
authors.lastname: Ikeda
authors.forename: Mariko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001707:Biopsy, Needle; D006528:Carcinoma, Hepatocellular / Q000401:mortality* / Q000473:pathology; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008111:Liver Function Tests; D008113:Liver Neoplasms / Q000401:mortality* / Q000473:pathology / Q000517:prevention & control; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000473:pathology; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D011994:Recombinant Proteins; D018570:Risk Assessment; D012720:Severity of Illness Index; D016019:Survival Analysis
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins