title: Low-dose pegylated interferon-α2a plus ribavirin therapy for elderly and/or cirrhotic patients with HCV genotype-1b and high viral load.
abstract: BACKGROUND
  Pegylated interferon (PEG-IFN) plus ribavirin therapy is still recommended for elderly and/or cirrhotic patients. This study examined whether sustained virological response (SVR) to low-dose PEG-IFN-α2a plus ribavirin therapy for elderly and/or cirrhotic patients could be predicted based on viral reduction within 2 weeks after therapy initiation or interleukin IL-(28B) polymorphism and viral mutations.
  
  
  METHODS
  Participants comprised 115 elderly (≥65 years) and/or cirrhotic patients with genotype-1b and high viral load. Reduced doses of PEG-IFN-α2a (90 μg/kg/week) and ribavirin (400-800 mg/day) were administered for 48-72 weeks based on virological response of each patient.
  
  
  RESULTS
  SVR was achieved in 34% (39/115), and treatment was discontinued in 15% (17/115). Univariate analysis identified age, α-fetoprotein, fibrosis marker, interferon sensitivity-determining region (ISDR), IL-28B polymorphism and level of viral reduction within 2 weeks as factors contributing significantly to SVR. However, no significant differences were noted in core amino acid substitutions. Multivariate analysis identified age, hyaluronic acid, ISDR and viral reduction as factors independently associated with SVR. Positive predictive value (PPV) and negative predictive value (NPV) of SVR based on the level of viral reduction at 2 weeks (cutoff level, 1.7 log IU/ml) were 83% and 84%, respectively. The PPV of SVR based on IL-28B major and ISDR mutant was 70%, and the NPV of SVR based on IL-28B minor and wild-type ISDR was 89%.
  
  
  CONCLUSIONS
  Evaluations of viral reduction at 2 weeks or both IL-28B and ISDR are useful to predict SVR to low-dose PEG-IFN-α2a plus ribavirin therapy for elderly and/or cirrhotic patients.
authors.affiliation: Second Department of Internal Medicine, Wakayama Medical University, Wakayama City, Japan. tamahide@wakayama-med.ac.jp.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Tamai
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Mori
authors.forename: Naoki
authors.initials: N
authors.lastname: Shingaki
authors.forename: Akira
authors.initials: A
authors.lastname: Kawashima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsukuda
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Higashi
authors.forename: Kosaku
authors.initials: K
authors.lastname: Moribata
authors.forename: Masanori
authors.initials: M
authors.lastname: Kawaguchi
authors.forename: Kazuki
authors.initials: K
authors.lastname: Ueda
authors.forename: Hisanobu
authors.initials: H
authors.lastname: Deguchi
authors.forename: Izumi
authors.initials: I
authors.lastname: Inoue
authors.forename: Takao
authors.initials: T
authors.lastname: Maekita
authors.forename: Mikitaka
authors.initials: M
authors.lastname: Iguchi
authors.forename: Jun
authors.initials: J
authors.lastname: Kato
authors.forename: Masao
authors.initials: M
authors.lastname: Ichinose
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000378:metabolism; D008103:Liver Cirrhosis / Q000209:etiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors; D016896:Treatment Outcome; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a