Serum levels of anti-NS4a and anti-NS5a predict treatment response of patients with chronic hepatitis C.
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.
Desombere
Isabelle
I
Center for Vaccinology, Ghent University and Hospital, Ghent, Belgium. Isabelle.desombere@ugent.be
Van Vlierberghe
Hans
H
Weiland
Ola
O
Hultgren
Catharina
C
Sällberg
Matti
M
Quiroga
Juan
J
Carreño
Vicente
V
Leroux-Roels
Geert
G
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
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