Relation of interferon therapy and hepatocellular carcinoma in patients with chronic hepatitis C. Osaka Hepatocellular Carcinoma Prevention Study Group

Ann Intern Med. 1998 Jul 15;129(2):94-9. doi: 10.7326/0003-4819-129-2-199807150-00005.


Background: The effect of interferon therapy on the incidence of hepatocellular carcinoma in chronic hepatitis C is poorly defined.

Objective: To compare the incidence of hepatocellular carcinoma in interferon-treated patients with chronic hepatitis C to that of historical controls and to examine whether response to therapy is related to incidence of hepatocellular carcinoma in patients with chronic hepatitis C.

Design: Retrospective cohort study.

Setting: One university hospital and seven university-affiliated hospitals.

Patients: 419 consecutive patients with chronic hepatitis C who started interferon therapy between January 1992 and December 1993 (interferon group) and 144 patients with chronic hepatitis C who had liver biopsy between January 1986 and December 1989 and did not receive interferon (controls).

Intervention: Patients in the interferon group received human lymphoblastoid interferon, recombinant interferon-alpha2a, or recombinant interferon-alpha2b for 6 months.

Measurements: The end point was development of hepatocellular carcinoma on abdominal ultrasonography or computed tomography. Sustained response was defined as persistent normalization of alanine aminotransferase (ALT) levels during interferon therapy and follow-up. Relapse was defined as a normal serum ALT level at the end of treatment with an increase to an abnormal level after cessation of treatment. Nonresponse included all other ALT patterns.

Results: Median follow-up in the interferon and control groups was 47.6 and 46.8 months, respectively. During follow-up, hepatocellular carcinoma was found in 28 interferon-treated patients and 19 controls. Cox proportional hazards regression analysis that included all patients revealed that interferon therapy (P=0.041), older age (P=0.003), greater histologic activity (P=0.029), and higher histologic stage (P=0.049) were independent factors associated with the development of hepatocellular carcinoma. The risk ratios for development of hepatocellular carcinoma in patients with sustained response, relapse, and nonresponse were 0.06 (95% CI, 0.01 to 0.46), 0.51 (CI, 0.20 to 1.27), and 0.95 (CI, 0.48 to 1.84), respectively, compared with controls.

Conclusions: The incidence of hepatocellular carcinoma was lower in patients with sustained response to interferon therapy than historical controls and nonresponders. Interferon therapy may decrease the risk for hepatocellular carcinoma in patients with chronic hepatitis C.

MeSH terms

  • Alanine Transaminase / blood
  • Carcinoma, Hepatocellular / etiology*
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / enzymology
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Liver Neoplasms / etiology*
  • Male
  • Middle Aged
  • Recombinant Proteins
  • Retrospective Studies
  • Statistics as Topic


  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Alanine Transaminase