CHRONIC HEPATITIS-C IN PATIENTS WITH NORMAL OR NEAR NORMAL ALANINE AMINOTRANSFERASE LEVELS - THE ROLE OF INTERFERON-ALPHA-2B THERAPY

Background/Aims: Interferon is the only approved therapy for chronic h epatitis occurring as a consequence of an infection with the hepatitis C virus, Because interferon is expensive, has a large number of untow ard effects and its efficacy is not guaranteed, many physicians limit their use of this therapy to those with histologically advanced but no t end-stage cirrhotic disease, Moreover, most cases are biopsied only after 6 months or more of abnormal alanine aminotransferase levels hav e been documented, The rationale for this approach to patients with he patitis C virus infection has not been demonstrated. Methods: In the p resent study, a total of 37 patients with alanine aminotransferase lev els <1.5 upper limits of normal (59 IU/l or less) who were HCV-RNA pos itive by reverse transcriptase polymerase chain reaction, were selecte d for interferon treatment, having been identified as having hepatitis C virus disease as the result of a screening Ab-HCV test confirmed wi th a positive radio immune blotting assay, Once identified, each subje ct underwent a percutaneous liver biopsy and was tested for the presen ce of HBsAg, Ab-HBs and HBV-DNA, All liver biopsies were read and grad ed according to the criteria of Knodell et al, Each subject was treate d with interferon alpha 2b 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 ser um on three consecutive monthly determinations, The study population c onsisted 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 we re presumed to have acquired their hepatitis C virus infection as a re sult 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 l evels, 9 subjects had chronic persistent hepatitis, 13 had chronic act ive hepatitis and 15 had chronic active hepatitis+cirrhosis documented by histopathologic assessment of their liver biopsies. Results: An in terferon response was achieved in 5/9 with chronic persistent hepatiti s, 11/13 with chronic active hepatitis and 8/15 with chronic active he patitis+cirrhosis for an overall response rate of 65%. Conclusions: Th is study has demonstrated that individuals who: 1) are hepatitis C vir us positive with serum alanine aminotransferase levels <1.5 X upper li mits of normal can have histologically advanced liver disease; 2) can respond to interferon therapy defined as clearance of detectable HCV-R NA in serum; and, 3) should be considered for interferon treatment. (C ) Journal of Hepatology.