Chronic hepatitis C in patients with normal or near normal alanine aminotransferase levels: the role of interferon alpha 2b therapy

J Hepatol. 1995 Nov;23(5):503-8. doi: 10.1016/0168-8278(95)80054-9.


Background/aims: Interferon is the only approved therapy for chronic hepatitis occurring as a consequence of an infection with the hepatitis C virus. Because interferon is expensive, has a large number of untoward effects and its efficacy is not guaranteed, many physicians limit their use of this therapy to those with histologically advanced but not end-stage cirrhotic disease. Moreover, most cases are biopsied only after 6 months or more of abnormal alanine aminotransferase levels have been documented. The rationale for this approach to patients with hepatitis C virus infection has not been demonstrated.

Methods: In the present study, a total of 37 patients with alanine aminotransferase levels < 1.5 upper limits of normal (59 IU/l or less) who were HCV-RNA positive by reverse transcriptase polymerase chain reaction, were selected for interferon treatment, having been identified as having hepatitis C virus disease as the result of a screening Ab-HCV test confirmed with a positive radio immune blotting assay. Once identified, each subject underwent a percutaneous liver biopsy and was tested for the presence of HBsAg, Ab-HBs and HBV-DNA. All liver biopsies were read and graded according to the criteria of Knodell et al. Each subject was treated with interferon a2b at a dose of 5 MU administered daily until a response was achieved (a minimum period of 6 months) or until a full year had elapsed. A response was defined as HCV-RNA negativity in serum on three consecutive monthly determinations. The study population consisted of 21 males and 16 females ranging in age from 17 to 72 years (mean 46.7 +/- 2.2 years). Their mean serum alanine aminotransferase level at the initiation of therapy was 37.5 +/- 2.1 IU/l with a range of 10-59 (normal values being 40 IU/l or less). 54% of the subjects were presumed to have acquired their hepatitis C virus infection as a result of a blood transfusion; 32% as a result of prior intravenous drug abuse; and 13% had no identifiable risk factor for hepatitis C virus. Despite having normal or near normal serum alanine aminotransferase levels, 9 subjects had chronic persistent hepatitis, 13 had chronic active hepatitis and 15 had chronic active hepatitis + cirrhosis documented by histopathologic assessment of their liver biopsies.

Results: An interferon response was achieved in 5/9 with chronic persistent hepatitis, 11/13 with chronic active hepatitis and 8/15 with chronic active hepatitis + cirrhosis for an overall response rate of 65%.

Conclusions: This study has demonstrated that individuals who: 1) are hepatitis C virus positive with serum alanine aminotransferase levels < 1.5 x upper limits of normal can have histologically advanced liver disease; 2) can respond to interferon therapy defined as clearance of detectable HCV-RNA in serum; and, 3) should be considered for interferon treatment.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Alanine Transaminase / blood*
  • Chronic Disease
  • Cost-Benefit Analysis
  • Female
  • Follow-Up Studies
  • Hepatitis C / drug therapy*
  • Hepatitis C / economics
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / economics
  • Interferon-alpha / therapeutic use*
  • Male
  • Middle Aged
  • Recombinant Proteins
  • Treatment Outcome


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