title: Serum levels of anti-NS4a and anti-NS5a predict treatment response of patients with chronic hepatitis C.
abstract: In order to understand better the clinical significance and prognostic value of antibody responses to HCV proteins and in search for parameters that may allow the early identification of non-sustained responders to therapy, antibody levels were measured against NS3, NS4a and NS5a at baseline in the serum of 120 patients chronically infected with HCV of genotype 1 that were classified as sustained responders, relapsers, or non-responders to therapy. The capacity of these antibody tests to predict therapy-outcome was evaluated. While no differences were observed in the anti-NS3 responses in these different response groups, anti-NS4a and anti-NS5a antibodies were observed more frequently and at higher titres in sustained responders versus non-responders or non-sustained responders (=non-responders + relapsers). Based on this observation, a combination of test results consisting of 'the absence of NS4a (AA 1687-1718) antibody at baseline and the presence of HCV-RNA exceeding 10(5) IU/ml after 1 week of treatment' was identified which predicts non-sustained response to treatment with 100% certainty. Replacing the HCV-RNA decision limit by a HCV-core antigen level of >15 pg/ml resulted in the same predictive value. The proposed algorithm also holds for patients treated with peg-interferon and ribavirin. In conclusion, in patients with chronic HCV infection, the decision to continue or stop treatment can be made after 1 week of treatment with (peg)-interferon alpha and ribavirin.
authors: Center for Vaccinology, Ghent University and Hospital, Ghent, Belgium. Isabelle.desombere@ugent.be
authors: Isabelle
authors: I
authors: Desombere
authors: Hans
authors: H
authors: Van Vlierberghe
authors: Ola
authors: O
authors: Weiland
authors: Catharina
authors: C
authors: Hultgren
authors: Matti
authors: M
authors: Sällberg
authors: Juan
authors: J
authors: Quiroga
authors: Vicente
authors: V
authors: Carreño
authors: Geert
authors: G
authors: Leroux-Roels
mesh_terms: D000465:Algorithms; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers; D002352:Carrier Proteins / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000097:blood*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons / Q000627:therapeutic use; D047908:Intracellular Signaling Peptides and Proteins; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000097:blood; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D014758:Viral Core Proteins / Q000097:blood; D017361:Viral Nonstructural Proteins / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D002352:Carrier Proteins; D018937:Hepatitis C Antibodies; D016898:Interferon-alpha; D007372:Interferons; D047908:Intracellular Signaling Peptides and Proteins; D012367:RNA, Viral; D012254:Ribavirin; D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C455041:NS4A cofactor peptide, Hepatitis C virus; C069130:nucleocapsid protein, Hepatitis C virus; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase