Linked Life Data

18537193

Source:http://linkedlifedata.com/resource/pubmed/id/18537193

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-7-10
pubmed:abstractText
A substantial proportion of hepatitis C virus (HCV)-1b-infected patients still do not respond to interferon-based therapy. This study aims to explore a predictive marker for the ultimate virological response of HCV-1b-infected patients treated with pegylated interferon/ribavirin (PEG-IFN/RBV) combination therapy. Nonstructural protein 5A (NS5A) sequences of HCV in the pretreated sera of 45 patients infected with HCV-1b were analyzed. The mean number of mutations in the variable region 3 (V3) plus its upstream flanking region of NS5A (amino acid 2334-2379), referred to as IFN/RBV resistance-determining region (IRRDR), was significantly higher for HCV isolates obtained from patients who later achieved sustained virological response (SVR) by PEG-IFN/RBV than for those in patients undergoing non-SVR. The receiver operating characteristic curve analysis estimated six mutations in IRRDR as the optimal threshold for SVR prediction. Indeed, 16 (76%) of 21 SVR, but only 2 (8%) of 24 non-SVR, had HCV with six or more mutations in IRRDR (IRRDR > or = 6) (P < 0.0001). All of 18 patients infected with HCV of IRRDR of 6 or greater examined showed a significant (> or =1 log) reduction or disappearance of serum HCV core antigen titers within 24 hours after initial dose of PEG-IFN/RBV, whereas 10 (37%) of 27 patients with HCV of IRRDR of 5 or less did (P < 0.0001). The positive predictive value of IRRDR of 6 or greater for SVR was 89% (16/18; P = 0.0007), with its negative predictive value for non-SVR being 81% (22/27; P = 0.0008). CONCLUSION: A high degree (> or =6) of sequence variation in IRRDR would be a useful marker for predicting SVR, whereas a less diverse (< or =5) IRRDR sequence predicts non-SVR.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1527-3350
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
38-47
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:18537193-Aged, pubmed-meshheading:18537193-Antiviral Agents, pubmed-meshheading:18537193-Consensus Sequence, pubmed-meshheading:18537193-Drug Therapy, Combination, pubmed-meshheading:18537193-Female, pubmed-meshheading:18537193-Genetic Variation, pubmed-meshheading:18537193-Genotype, pubmed-meshheading:18537193-Hepacivirus, pubmed-meshheading:18537193-Hepatitis C, Chronic, pubmed-meshheading:18537193-Humans, pubmed-meshheading:18537193-Interferon-alpha, pubmed-meshheading:18537193-Male, pubmed-meshheading:18537193-Middle Aged, pubmed-meshheading:18537193-Mutation, pubmed-meshheading:18537193-Polyethylene Glycols, pubmed-meshheading:18537193-Predictive Value of Tests, pubmed-meshheading:18537193-Recombinant Proteins, pubmed-meshheading:18537193-Ribavirin, pubmed-meshheading:18537193-Treatment Outcome, pubmed-meshheading:18537193-Viral Nonstructural Proteins
pubmed:year
2008
pubmed:articleTitle
Sequence variation in hepatitis C virus nonstructural protein 5A predicts clinical outcome of pegylated interferon/ribavirin combination therapy.
pubmed:affiliation
Division of Microbiology, Kobe University Graduate School of Medicine, Kobe, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't