title: Peginterferon alfa-2a (40 kilodaltons) and ribavirin in patients with chronic hepatitis C and normal aminotransferase levels.
abstract: OBJECTIVE
  Patients with chronic hepatitis C and persistently normal alanine aminotransferase (ALT) levels have been routinely excluded from large randomized treatment trials; consequently, the efficacy and safety of antiviral therapy in this population are unknown.
  
  
  METHODS
  Patients with at least 3 normal ALT values over an 18-month period were randomized (3:3:1) to treatment with peginterferon alfa-2a 180 mug/wk plus ribavirin 800 mg/day for 24 weeks (212 patients), the same combination for 48 weeks (210 patients), or no treatment (69 patients) in a multinational study. All patients were monitored for 72 weeks. The primary measure of efficacy was sustained virologic response (SVR), defined as undetectable serum hepatitis C virus (HCV) RNA by qualitative polymerase chain reaction at the end of 24 weeks of untreated follow-up.
  
  
  RESULTS
  No patient cleared HCV RNA in the untreated control group. SVR rates of 30% and 52% were obtained in the 24- and 48-week treatment groups, respectively. In patients infected with HCV genotype 1, SVR rates of 13% and 40% were obtained with 24 and 48 weeks of treatment, respectively (P < .0001). In patients infected with genotypes 2 or 3, SVR rates were 72% and 78% with 24 and 48 weeks of treatment, respectively (P = .452). Treatment-related flares in ALT activity were not observed.
  
  
  CONCLUSIONS
  The efficacy and safety of peginterferon alfa-2a and ribavirin combination therapy in patients with chronic hepatitis C and persistently normal ALT levels are similar to that in patients with elevated ALT levels. The indication for treatment of hepatitis C can be evaluated independently from baseline ALT activity.
authors.affiliation: Saarland University Hospital, Homburg/Saar, Germany. zeuzem@uniklinik-saarland.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Moisés
authors.initials: M
authors.lastname: Diago
authors.forename: Edward
authors.initials: E
authors.lastname: Gane
authors.forename: K Rajender
authors.initials: KR
authors.lastname: Reddy
authors.forename: Paul
authors.initials: P
authors.lastname: Pockros
authors.forename: Daniele
authors.initials: D
authors.lastname: Prati
authors.forename: Mitchell
authors.initials: M
authors.lastname: Shiffman
authors.forename: Patrizia
authors.initials: P
authors.lastname: Farci
authors.forename: Norman
authors.initials: N
authors.lastname: Gitlin
authors.forename: Christopher B
authors.initials: CB
authors.lastname: O'Brien
authors.forename: François
authors.initials: F
authors.lastname: Lamour
authors.forename: Pilar
authors.initials: P
authors.lastname: Lardelli
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D000410:Alanine Transaminase; C100416:peginterferon alfa-2a