title: A randomized, controlled trial of maintenance interferon therapy for patients with chronic hepatitis C virus and persistent viremia.
abstract: OBJECTIVE
  : At least half of patients with chronic hepatitis C virus (HCV) fail to respond to interferon or interferon/ribavirin therapy. Histological improvement is observed in some nonresponders. We conducted a randomized, controlled trial to determine if maintenance interferon therapy could prevent histological progression in this subset of nonresponders.
  
  
  METHODS
  Fifty-three patients with chronic HCV were enrolled. All were HCV-RNA positive after 6 months of treatment with interferon alfa-2b but had a histological response. Twenty-seven of the patients were randomly assigned to continue interferon (3 MU 3 times weekly) for 24 months; 26 patients discontinued treatment and were observed prospectively. Alanine aminotransferase (ALT) level and HCV-RNA titer were monitored, and liver biopsy was repeated every 12 months.
  
  
  RESULTS
  Before interferon therapy, the 2 groups were well matched for all demographic factors, serum ALT (94.0 +/- 15.6), log HCV-RNA titer (5. 85 +/- 0.15 copies/mL), histology score (9.5 +/- 0.2), and percentage with cirrhosis (25%). After 6 months of treatment, significant reductions (P < 0.05) in serum ALT level (62.6 +/- 9.6), log HCV-RNA titer (4.79 +/- 0.13 copies/mL), and hepatic inflammation (4.0 +/- 0.2) were observed. These improvements were maintained in the patients randomized to continue interferon. Stopping treatment was associated with an increase in serum ALT, log HCV-RNA, and hepatic inflammation back to baseline. After 30 months of treatment, mean fibrosis score declined from 2.5 to 1.7 and 80% of patients had histological improvement (P < 0.03). Discontinuation of interferon was associated with an increase in mean fibrosis score from 2.2 to 2.4 and worsening of hepatic histology in 30% of patients (P < 0.01).
  
  
  CONCLUSIONS
  These data support the hypothesis that maintenance interferon may prevent histological progression of chronic HCV in patients who remain viremic.
authors.affiliation: Hepatology Section, Medical College of Virginia Commonwealth University, Richmond, Virginia, USA. mshiffma@hsc.vcu.edu
authors.forename: M L
authors.initials: ML
authors.lastname: Shiffman
authors.forename: C M
authors.initials: CM
authors.lastname: Hofmann
authors.forename: M J
authors.initials: MJ
authors.lastname: Contos
authors.forename: V A
authors.initials: VA
authors.lastname: Luketic
authors.forename: A J
authors.initials: AJ
authors.lastname: Sanyal
authors.forename: R K
authors.initials: RK
authors.lastname: Sterling
authors.forename: A
authors.initials: A
authors.lastname: Ferreira-Gonzalez
authors.forename: A S
authors.initials: AS
authors.lastname: Mills
authors.forename: C
authors.initials: C
authors.lastname: Garret
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / 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; D014766:Viremia / Q000188:drug therapy*
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D000410:Alanine Transaminase