Document Detail

Several factors including ITPA polymorphism influence ribavirin-induced anemia in chronic hepatitis C.
MedLine Citation:
PMID:  23139603     Owner:  NLM     Status:  MEDLINE    
AIM: To construct formulae for predicting the likelihood of ribavirin-induced anemia in pegylated interferon α plus ribavirin for chronic hepatitis C.
METHODS: Five hundred and sixty-one Japanese patients with hepatitis C virus genotype 1b who had received combination treatment were enrolled and assigned randomly to the derivation and confirmatory groups. Single nucleotide polymorphisms at or nearby ITPA were genotyped by real-time detection polymerase chain reaction. Factors influencing significant anemia (hemoglobin concentration < 10.0 g/dL at week 4 of treatment) and significant hemoglobin decline (declining concentrations > 3.0 g/dL at week 4) were analyzed using multiple regression analyses. Prediction formulae were constructed by significantly independent factors.
RESULTS: Multivariate analysis for the derivation group identified four independent factors associated with significant hemoglobin decline: hemoglobin decline at week 2 [P = 3.29 × 10(-17), odds ratio (OR) = 7.54 (g/dL)], estimated glomerular filtration rate [P = 2.16 × 10(-4), OR = 0.962 (mL/min/1.73 m(2))], rs1127354 (P = 5.75 × 10(-4), OR = 10.94) and baseline hemoglobin [P = 7.86 × 10(-4), OR = 1.50 (g/dL)]. Using the model constructed by these factors, positive and negative predictive values and predictive accuracy were 79.8%, 88.8% and 86.2%, respectively. For the confirmatory group, they were 83.3%, 91.0% and 88.3%. These factors were closely correlated with significant anemia. However, the model could not be constructed, because no patients with rs1127354 minor genotype CA/AA had significant anemia.
CONCLUSION: Reliable formulae for predicting the likelihood of ribavirin-induced anemia were constructed. Such modeling may be useful in developing individual tailoring and optimization of ribavirin dosage.
Akihito Tsubota; Noritomo Shimada; Hiroshi Abe; Kai Yoshizawa; Rie Agata; Yoko Yumoto; Makiko Ika; Yoshihisa Namiki; Keisuke Nagatsuma; Hiroshi Matsudaira; Kiyotaka Fujise; Norio Tada; Yoshio Aizawa
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  World journal of gastroenterology : WJG     Volume:  18     ISSN:  2219-2840     ISO Abbreviation:  World J. Gastroenterol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-09     Completed Date:  2013-11-12     Revised Date:  2014-05-20    
Medline Journal Info:
Nlm Unique ID:  100883448     Medline TA:  World J Gastroenterol     Country:  China    
Other Details:
Languages:  eng     Pagination:  5879-88     Citation Subset:  IM    
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MeSH Terms
Anemia / blood,  chemically induced*,  enzymology,  genetics*
Antiviral Agents / adverse effects*
Biological Markers / blood
Chi-Square Distribution
Drug Therapy, Combination
Genetic Predisposition to Disease
Hemoglobins / metabolism
Hepatitis C, Chronic / diagnosis,  drug therapy*
Interferon-alpha / therapeutic use
Logistic Models
Middle Aged
Multivariate Analysis
Odds Ratio
Polyethylene Glycols / therapeutic use
Polymorphism, Single Nucleotide*
Pyrophosphatases / genetics*
Recombinant Proteins / therapeutic use
Ribavirin / adverse effects*
Risk Assessment
Risk Factors
Reg. No./Substance:
0/Antiviral Agents; 0/Biological Markers; 0/Hemoglobins; 0/Interferon-alpha; 0/Polyethylene Glycols; 0/Recombinant Proteins; 0/peginterferon alfa-2a; 0/peginterferon alfa-2b; 49717AWG6K/Ribavirin; EC 3.6.1.-/Pyrophosphatases; EC protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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