Eradication of Hepatitis C Virus RNA after Alpha-Interferon Therapy

  1. Raffaella Romeo, MD;
  2. Stanislas Pol, MD, PhD;
  3. Pierre Berthelot, MD; and
  4. Christian Brechot, MD, PhD
  1. From the University of Milan, Milan, Italy and Centre Hopitalier Universitaire Necker, Paris, France. Requests for Reprints: Raffaella Romeo, MD, Institute of Internal Medicine, University of Milan, via Pace, 9-20122 Milan, Italy. Grant Support: By Institut National de la Sante et Recherche Medicale, Caisse National Assurance Maladie, Association pour la Recherche contre le Cancer, and the European Community. Dr. Romeo is the recipient of a fellowship from Istituto Superiore di Sanita, Rome, Italy.

    Hepatitis C virus (HCV) is the main cause of chronic non-A, non-B hepatitis developing after transfusion [1]; many patients (50% to 60%) become chronic carriers, of whom as many as 20% develop cirrhosis. In approximately 25% of patients, referred to as long-term responders, α-interferon therapy can lead to a sustained and complete normalization of aminotransferase activity. The remaining patients either do not respond or relapse during or shortly after treatment [2].

    Polymerase chain reaction (PCR) and the new branched-DNA method for detecting HCV RNA have greatly facilitated the assessment of specific treatment efficacy [3]. These techniques can be used to detect ongoing HCV replication and the persistence of HCV genomes in the liver and peripheral blood mononuclear cells [4]. However, they have not yet been used to evaluate hepatic, serum, and peripheral blood mononuclear cell-HCV RNA status in long-term responders to α-interferon.

    We evaluate whether α-interferon therapy leads to complete eradication of the virus in some long-term responders because the HCV genome does not integrate host-cell DNA, and its persistence thus depends on HCV RNA replication.

    Methods

    Between January 1990 and March 1993, 348 anti-HCV-positive patients were referred to our hepatology unit. The 189 patients who were given α-interferon therapy met the following criteria: hypertransaminasemia, detectable HCV viremia, and biopsy-proven chronic hepatitis. The 159 patients who were not treated had either a relative contraindication (for example, renal transplantation, hemodialysis, human immunodeficiency virus [HIV]-associated infection, chronic alcoholism, …

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