title: Hepatocarcinogenesis in chronic hepatitis C patients achieving a sustained virological response to interferon: significance of lifelong periodic cancer screening for improving outcomes.
abstract: BACKGROUND
  Due to advances in interferon (IFN) therapy for chronic hepatitis C, most elderly patients, and even many of those with advanced hepatic fibrosis, now achieve a sustained virological response (SVR). However, carcinogenesis remains problematic in these patients. Hence, we aimed to elucidate risk factors for hepatocarcinogenesis in SVR patients and to present an appropriate follow-up protocol for improving outcomes.
  
  
  METHODS
  We retrospectively studied 562 consecutive SVR patients for a median observation period of 4.8 years.
  
  
  RESULTS
  Hepatocellular carcinoma was diagnosed in 31 patients (5.5%). Respective cumulative incidences were 3.1, 10.1, and 15.9% at 5, 10, and 15 years after completion of IFN therapy. The proportional hazards model identified moderate or advanced fibrosis stage, advanced age, habitual alcohol consumption, and alpha-fetoprotein elevation as determinants of carcinogenesis, with hazard ratios of 10.7 (p < 0.001), 4.1 (p < 0.01), 3.9 (p < 0.01), and 2.6 (p < 0.05), respectively. Carcinoma was diagnosed in 26% of patients more than 10 years after completion of IFN therapy. Unexpectedly, F2 fibrosis was detected in 42% of these patients. The 5-year survival rate was 93% in the patients who had received periodic cancer screening but only 60% in those who had not.
  
  
  CONCLUSIONS
  We recommend that SVR patients be observed at 6-month intervals, at a minimum, to facilitate diagnosis at an early stage, for as long as possible after completion of therapy even if not at an advanced stage of fibrosis.
authors: Department of Hepatology, Steel Memorial Yawata Hospital, 1-1-1 Harunomachi, Yahatahigashi-ku, Kitakyushu, 805-8508, Japan, naoyamgggg@gmail.com.
authors: Naoki
authors: N
authors: Yamashita
authors: Aritsune
authors: A
authors: Ohho
authors: Akihiro
authors: A
authors: Yamasaki
authors: Miho
authors: M
authors: Kurokawa
authors: Kazuhiro
authors: K
authors: Kotoh
authors: Eiji
authors: E
authors: Kajiwara
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000453:epidemiology / Q000821:virology; D055088:Early Detection of Cancer; D005260:Female; D005500:Follow-Up Studies; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D015994:Incidence; D007370:Interferon Type I / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000627:therapeutic use; D016899:Interferon-beta / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008103:Liver Cirrhosis / Q000821:virology; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000821:virology; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D007370:Interferon Type I; D016898:Interferon-alpha; D016899:Interferon-beta