title: Long-term histologic improvement and loss of detectable intrahepatic HCV RNA in patients with chronic hepatitis C and sustained response to interferon-alpha therapy.
abstract: BACKGROUND
  Less than 20% of patients with chronic hepatitis C have a sustained response to interferon-alpha therapy. The long-term benefit of interferon-alpha with regard to hepatic viral clearance and histologic improvement remains unknown.
  
  
  OBJECTIVE
  To determine the long-term biochemical, virologic, and histologic outcomes in patients with chronic hepatitis C who have a sustained response to interferon-alpha therapy.
  
  
  METHODS
  Prospective cohort study.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  80 patients who had chronic hepatitis C, had a sustained biochemical and virologic response to interferon-alpha therapy, and were followed for at least 12-months.
  
  
  METHODS
  Serum hepatitis C virus (HCV) RNA detected by polymerase chain reaction (PCR); HCV genotyping determined by line probe assay; liver histologic studies; liver HCV RNA detected by PCR on frozen liver tissue samples (in 27 patients); and repeated measurements of serum alanine aminotransferase (ALT) levels. Liver biopsy was done before treatment in all 80 patients, and at least one biopsy was done in 69 patients 1 to 6 years after treatment.
  
  
  RESULTS
  The 80 patients had follow-up 1 to 7.6 years (mean +/- SD, 4.0 +/- 2.0 years) after interferon-alpha treatment. The follow-up period was 1, 2, 3, 4, 5, 6, and more than 6 years in 11, 13, 14, 18, 10, 12, and 2 patients, respectively, after the end of therapy. During the entire follow-up period, 93% (95% CI, 84% to 97%) of patients had persistently normal serum ALT levels. Serum HCV RNA remained undetectable in 96% (CI, 89% to 99%) of patients. A comparison of liver histologic findings before and 1 to 6.2 years after interferon-alpha treatment showed a clear improvement in 94% (CI, 83% to 99%) of patients. In 62% of patients, the last biopsy done showed normal or nearly normal histologic findings. Liver HCV RNA was detectable before treatment in all 13 patients tested and was undetectable 1 to 5 years after treatment in all 27 patients tested.
  
  
  CONCLUSIONS
  In patients with chronic hepatitis C who have persistently normal serum ALT levels and no detectable serum HCV RNA 6 months after interferon-alpha therapy, a long-term sustained biochemical and virologic response is generally seen. This response is associated with an absence of detectable intrahepatic HCV RNA and marked histologic improvement.
authors.affiliation: Hôpital Beaujon, Clichy, France.
authors.forename: P
authors.initials: P
authors.lastname: Marcellin
authors.forename: N
authors.initials: N
authors.lastname: Boyer
authors.forename: A
authors.initials: A
authors.lastname: Gervais
authors.forename: M
authors.initials: M
authors.lastname: Martinot
authors.forename: M
authors.initials: M
authors.lastname: Pouteau
authors.forename: C
authors.initials: C
authors.lastname: Castelnau
authors.forename: A
authors.initials: A
authors.lastname: Kilani
authors.forename: J
authors.initials: J
authors.lastname: Areias
authors.forename: A
authors.initials: A
authors.lastname: Auperin
authors.forename: J P
authors.initials: JP
authors.lastname: Benhamou
authors.forename: C
authors.initials: C
authors.lastname: Degott
authors.forename: S
authors.initials: S
authors.lastname: Erlinger
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000473:pathology* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000201:enzymology / Q000473:pathology; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood*; D011994:Recombinant Proteins
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D000410:Alanine Transaminase