Effect of interferon treatment on serum 2',5'-oligoadenylate synthetase levels in hepatitis C-infected patients.
Interferon (IFN) is widely used for patients with hepatitis C. Less than half of treated patients respond to IFN therapy, however, and increased resistance to IFN is particularly observed in genotype 1b patients. Recently, genotype 1b patients with the wild type sequence in the NS5A gene were shown to be resistant to therapy, suggesting that the NS5A protein may be involved to IFN resistance. Thus, we investigated the serum 2',5'-oligoadenylate synthetase (2',5'-OAS) levels before and during IFN treatment. In addition, other biochemical markers and NS5A mutations were also examined in 30 HCV genotype 1b-positive patients. Before IFN treatment, 2',5'-OAS activity in sera was significantly lower in wild type patients than in mutant type patients. All patients were subsequently enrolled in IFN therapy, and 2',5'-OAS activity was elevated both in wild and mutant type patients, irrespective of the number of mutations in NS5A. Logistic regression analysis revealed that clearance of serum HCV RNA was independently related to the pretreatment viral load and NS5A mutations, but not to serum 2',5'-OAS activity. We concluded that the NS5A protein, that is associated with the outcome of IFN therapy, affects the kinetics of IFN-induced molecules, such as 2', 5'-OAS. 2',5'-OAS activity does not, however, seem to be related to long-term virological response to IFN therapy.
Murashima
S
S
Kurume University Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Japan. mura@med.kurume-u.ac.jp
Kumashiro
R
R
Ide
T
T
Miyajima
I
I
Hino
T
T
Koga
Y
Y
Ishii
K
K
Ueno
T
T
Sakisaka
S
S
Sata
M
M
D015088:2',5'-Oligoadenylate Synthetase / Q000097:blood*; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D006526:Hepatitis C / Q000188:drug therapy* / Q000201:enzymology / Q000821:virology; D006801:Humans; D007372:Interferons / Q000494:pharmacology / Q000627:therapeutic use*; D009154:Mutation; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000502:physiology*; D012324:RNA-Dependent RNA Polymerase
D015088:2',5'-Oligoadenylate Synthetase; D000998:Antiviral Agents; D007372:Interferons; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase