title: Early prediction of sustained virological response at day 3 of treatment with albinterferon-alpha-2b in patients with genotype 2/3 chronic hepatitis C.
abstract: BACKGROUND
  Albinterferon-alpha-2b (albIFN) is a long-acting fusion polypeptide composed of albumin and IFN-alpha-2b. In a phase 2 study of albIFN 1500 mug q2wk or q4wk in patients with genotype 2/3 chronic hepatitis C, albIFN demonstrated sustained virological response (SVR) rates of 62-77% (intent-to-treat population).
  
  
  OBJECTIVE
  To assess the association of initial viral kinetics during albIFN therapy with baseline factors and SVR prediction.
  
  
  METHODS
  In all, 43 patients were treated with albIFN 1500 mug (q2wk/q4wk) plus ribavirin (RBV) 800 mg/day for 24 weeks. Hepatitis C virus (HCV)-RNA levels were measured by real-time polymerase chain reaction, insulin resistance by homeostasis model assessment of insulin resistance (HOMA-IR) and serum albIFN levels by enyzme-linked immunosorbent assay. Prediction analysis was performed in a per protocol 28-patient subset who were > or =80% adherent to albIFN/RBV and had HCV-RNA levels measured at treatment day 3.
  
  
  RESULTS
  Day-3 HCV-RNA level and first-phase viral decline as well as second-phase slope of viral decline were significantly associated with SVR. In adherent patients, 82.1% had a day-3 viral load <4.2 log(10) IU/ml or first-phase decline >1.25 log(10) IU/ml, which was predictive of SVR, both positively (95.7%; sensitivity: 100%) and negatively (100%; specificity: 83.3%). As low first-phase decline was associated with a high pretreatment HOMA-IR index (P=0.004) and a low day-3 serum albIFN level (P=0.01).
  
  
  CONCLUSIONS
  First-phase viral decline with albIFN/RBV was predictive of SVR in this study and may be modulated in part by IR.
authors.affiliation: Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel. neumann@mail.biu.ac.il
authors.forename: Avidan U
authors.initials: AU
authors.lastname: Neumann
authors.forename: Vincent G
authors.initials: VG
authors.lastname: Bain
authors.forename: Eric M
authors.initials: EM
authors.lastname: Yoshida
authors.forename: Keyur
authors.initials: K
authors.lastname: Patel
authors.forename: Erik
authors.initials: E
authors.lastname: Pulkstenis
authors.forename: G Mani
authors.initials: GM
authors.lastname: Subramanian
mesh_terms: D000328:Adult; D000418:Albumins / Q000008:administration & dosage*; D000998:Antiviral Agents / Q000008:administration & dosage*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007333:Insulin Resistance; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage
chemical_list: D000418:Albumins; D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; C531108:albinterferon alfa-2b