title: Sustained response to combination therapy in patients with chronic hepatitis C who failed to respond to interferon.
abstract: OBJECTIVE
  The best treatment for chronic hepatitis C patients who do not respond to interferon is still unknown. Reported rates of response to treatment vary as the result of heterogeneous definitions of non-responders and small study size.
  
  
  METHODS
  One hundred nineteen hepatitis C virus (HCV) RNA-positive non-responders to high-dose interferon monotherapy received alpha-interferon, 5 MU tiw plus oral ribavirin, 1000-1200 mg/day for 48 weeks (Group A, n=74) or alpha-interferon, 5 MU daily for 4 weeks, followed by 5 MU tiw plus oral ribavirin, 1000-1200 mg/day for 44 weeks (Group B, n=45) according to the Institution where they were followed. Persistently normal alanine aminotransferase and negative HCV RNA up to 72 weeks from treatment onset defined a sustained response.
  
  
  RESULTS
  Eighteen patients discontinued treatment (13 developed anemia, two mucositis, one granulocytopenia; two were dropouts), none for serious adverse events. There were 24 (20%) sustained responders, with similar final response rates in Groups A and B. Sustained response was more frequent in patients aged </=40 years (36% vs. 13%; P=0.006) and in those with non-1 genotype (44% vs. 14%; P=0.002). Among genotype 1 patients, the younger ones showed higher response rates (32% vs. 7%; P=0.005). Compared with patients harboring non-1 genotypes, the odds ratio of being a non-responder was 1.68 (confidence interval (CI): 0.53-5.37; P=0.381) in younger genotype 1 patients and 9.53 (CI: 2.84-32; P<0.001) in older genotype 1 patients.
  
  
  CONCLUSIONS
  Chronic hepatitis C patients who are non-responders to interferon monotherapy and infected by non-1 genotypes should undergo re-treatment with combination therapy. Treatment should be extended to younger genotype 1 patients who are more susceptible to liver disease worsening because of longer life expectancy and have a higher probability of being long lasting responders than their older counterparts.
authors.affiliation: Dipartimento di Medicina Interna, Ospedale Maggiore IRCCS, Università di Milano, Pad Granelli, Via F Sforza 35, 20122 Milan, Italy. silvia.fargion@unimi.it
authors.forename: Silvia
authors.initials: S
authors.lastname: Fargion
authors.forename: Savino
authors.initials: S
authors.lastname: Bruno
authors.forename: Mauro
authors.initials: M
authors.lastname: Borzio
authors.forename: Pier Maria
authors.initials: PM
authors.lastname: Battezzati
authors.forename: Franco
authors.initials: F
authors.lastname: Bissoli
authors.forename: Roberto
authors.initials: R
authors.lastname: Ceriani
authors.forename: Annarosa
authors.initials: A
authors.lastname: Orlandi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Maraschi
authors.forename: Alberto
authors.initials: A
authors.lastname: Chiesa
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Morini
authors.forename: Anna Ludovica
authors.initials: AL
authors.lastname: Fracanzani
authors.forename: Andrea
authors.initials: A
authors.lastname: Crosignani
authors.forename: Gemino
authors.initials: G
authors.lastname: Fiorelli
authors.forename: Mauro
authors.initials: M
authors.lastname: Podda
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012254:Ribavirin