title: First phase hepatitis c viral kinetics in previous nonresponders patients.
abstract: A large proportion of patients fails to respond to treatment for hepatitis C. Initiation of interferon therapy is associated with a rapid first phase decline in viremia, reflecting inhibition of viral production or release from infected cells. We characterized first phase viral kinetics in previous nonresponder patients and compared the antiviral efficacy of interferon in nonresponders to that observed in naive patients. Twenty nonresponders with genotype 1 infection were evaluated. Ten received a single 15 mcg dose of interferon alfacon-1 and ten were given a 30 mcg dose. Viral kinetic data from previously untreated historical control patients with genotype 1 infection who received 9 mcg (n = 12) or 15 mcg (n = 13) of interferon alfacon-1 provided a basis for comparison. Antiviral efficacy was evaluated by calculating the reduction in HCV RNA levels during the first 24 h after interferon administration (log effectiveness). Hepatitis C virus levels decreased exponentially in previous nonresponder patients. Non-responders treated with 30 mcg of interferon alfacon-1 exhibited a greater log drop than non-responders receiving 15 mcg (P = 0.01). The log effectiveness of 15 mcg of interferon alfacon-1 in nonresponders was similar to 9 mcg in naives and was significantly < 15 mcg (P = 0.04) in naïve patients. The 30 mcg dose provided similar log effectiveness in nonresponders compared with 15 mcg in naive patients and exceeded the log effectiveness of 9 mcg in previously untreated patients (P = 0.035). Nonresponders who had greater than a 50% decrease in HCV RNA level from baseline at the end of previous treatment had a larger reduction in viral load at 24 h compared with those who had not achieved that level of response with prior therapy (P = 0.04). In conclusion, the log effectiveness of interferon was lower in nonresponders compared with treatment naive patients. The difference in antiviral effectiveness in previous nonresponders was overcome by higher interferon doses.
authors.affiliation: Section of Hepatology, RUSH-Presbyterian-St. Luke's Medical Center; University of Illinois at Chicago, Chicago, IL 60612, USA. scotler@rush.edu
authors.forename: S J
authors.initials: SJ
authors.lastname: Cotler
authors.forename: J E
authors.initials: JE
authors.lastname: Layden
authors.forename: A U
authors.initials: AU
authors.lastname: Neumann
authors.forename: D M
authors.initials: DM
authors.lastname: Jensen
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000821:virology*; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage / Q000627:therapeutic use; D016898:Interferon-alpha; D008297:Male; D015233:Models, Statistical; D012367:RNA, Viral / Q000097:blood* / Q000187:drug effects / Q000235:genetics; D011994:Recombinant Proteins; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D007370:Interferon Type I; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; C050739:interferon alfacon-1