title: Caspase activation is required for antiviral treatment response in chronic hepatitis C virus infection.
abstract: Only half of patients with chronic hepatitis C virus (HCV) infection and genotype-1 show a sustained antiviral response to the current antiviral therapy. The reason this treatment fails is unclear, and no reliable marker exists that predicts the treatment outcome. In the present study, we investigated the apoptotic activation of caspases in HCV patients undergoing antiviral therapy with regard to the treatment outcome. We determined caspase activation in sera from patients who were either responding or nonresponding to antiviral therapy by using two novel caspase assays, an immunological and a luminometric enzyme test. We found that compared with nonresponding individuals, responding patients showed significantly (P < .05) increased caspase activity, which was closely correlated with virus elimination (r = 0.81). The cutoff value of serum caspase activity was determined, which correctly predicted the treatment outcome with a sensitivity of 70% and a specificity of 82% (area under the curve 0.845; 95% CI). In conclusion, hepatic caspase activity might play a role in HCV clearance and could also predict the efficacy of antiviral therapy.
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Xandra
authors.initials: X
authors.lastname: Volkmann
authors.forename: Markus
authors.initials: M
authors.lastname: Cornberg
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
authors.forename: Frank
authors.initials: F
authors.lastname: Lehner
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.forename: Klaus
authors.initials: K
authors.lastname: Schulze-Osthoff
authors.forename: Heike
authors.initials: H
authors.lastname: Bantel
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D020169:Caspases / Q000097:blood* / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011336:Probability; D012372:ROC Curve; D011994:Recombinant Proteins; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D020169:Caspases