title: Interferon alpha treatment of chronic hepatitis C in patients with evidence for co-existent autoimmune dysregulation.
abstract: OBJECTIVE
  We performed a prospective nonrandomized clinical trial to demonstrate that Interferon (IFN) treatment of individuals with chronic hepatitis C virus (HCV) positive hepatitis (CH-C) and serologic and/or histologic evidence of autoimmune dysregulation is feasible and whether the benefits of successfully treating CH-C are outweighed by the risk of exacerbating Autoimmune Chronic Active Hepatitis (ACAH).
  
  
  METHODS
  23 patients with positive autoimmune dysregulation markers underwent a 6 month course of IFN treatment for chronic HCV hepatitis and were followed for a total of 12 months. Patients were treated with 5 MU of a2b IFN administered subcutaneously 7 days a week for 6 months. Complete blood counts and a panel of liver enzymes were monitored weekly for 4 weeks and then monthly for an additional 11 months (6 months of therapy and 6 months of follow-up). Serum auto-antibodies titers were determined prior to treatment, at the end of the treatment and again after 6 months of follow-up. A liver biopsy was performed prior to, and at the end of treatment and again at 12 months.
  
  
  RESULTS
  Using the standard ALT criteria for defining a response to IFN therapy, 14 (61%) patients experienced a full response and 3 (13%) experienced a partial response. Forty-three percent of the full responders and 33% of the partial responders experienced a relapse during the follow-up. The titer of each of the previously positive autoantibodies either remained unchanged or increased by 1 or 2 dilutions. No clinical exacerbations of a co-existent ACAH were observed.
  
  
  CONCLUSIONS
  Individuals with combined CH-C and one or more markers of autoimmune dysregulation can be treated successfully with IFN. Such treatment does not necessarily increase or exacerbate co-existent ACAH and elevate the serum ALT level. In those who clear HCV-RNA as a result of IFN, the liver histology shifts from one consistent with CH-C to resembling ACAH.
authors.affiliation: Oklahoma Transplant Institute, Baptist Medical Center of Oklahoma, Oklahoma City, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Van Thiel
authors.forename: P J
authors.initials: PJ
authors.lastname: Molloy
authors.forename: L
authors.initials: L
authors.lastname: Friedlander
authors.forename: R J
authors.initials: RJ
authors.lastname: Kania
authors.forename: S
authors.initials: S
authors.lastname: Fagiuoli
authors.forename: P
authors.initials: P
authors.lastname: Caraceni
authors.forename: H I
authors.initials: HI
authors.lastname: Wright
authors.forename: N
authors.initials: N
authors.lastname: Zuhdi
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D001323:Autoantibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000276:immunology*; D000075202:Contraindications; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006505:Hepatitis / Q000175:diagnosis / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology / Q000628:therapy*; D006521:Hepatitis, Chronic / Q000276:immunology / Q000628:therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins; D012307:Risk Factors; D013997:Time Factors
chemical_list: D000998:Antiviral Agents; D001323:Autoantibodies; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins