Document Detail


Model incorporating the ITPA genotype identifies patients at high risk of anemia and treatment failure with pegylated-interferon plus ribavirin therapy for chronic hepatitis C.
MedLine Citation:
PMID:  23297176     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
This study aimed to develop a model for predicting anemia using the inosine triphosphatase (ITPA) genotype and to evaluate its relationship with treatment outcome. Patients with genotype 1b chronic hepatitis C (n = 446) treated with peg-interferon alpha and ribavirin (RBV) for 48 weeks were genotyped for the ITPA (rs1127354) and IL28B (rs8099917) genes. Data mining analysis generated a predictive model for anemia (hemoglobin (Hb) concentration <10 g/dl); the CC genotype of ITPA, baseline Hb <14.0 g/dl, and low creatinine clearance (CLcr) were predictors of anemia. The incidence of anemia was highest in patients with Hb <14.0 g/dl and CLcr <90 ml/min (76%), followed by Hb <14.0 g/dl and ITPA CC (57%). Patients with Hb ≥14.0 g/dl and ITPA AA/CA had the lowest incidence of anemia (17%). Patients with two predictors (high-risk) had a higher incidence of anemia than the others (64% vs. 28%, P < 0.0001). At baseline, the IL28B genotype was a predictor of a sustained virological response [adjusted odds ratio 9.88 (95% confidence interval 5.01-19.48), P < 0.0001]. In patients who achieved an early virological response, the IL28B genotype was not associated with a sustained virological response, while a high risk of anemia was a significant negative predictor of a sustained virological response [0.47 (0.24-0.91), P = 0.026]. For high-risk patients with an early virological response, giving >80% of the planned RBV dose increased sustained virological responses by 24%. In conclusion, a predictive model incorporating the ITPA genotype could identify patients with a high risk of anemia and reduced probability of sustained virological response. J. Med. Virol. © 2013 Wiley Periodicals, Inc.
Authors:
Masayuki Kurosaki; Yasuhito Tanaka; Nao Nishida; Naoya Sakamoto; Nobuyuki Enomoto; Kentaro Matsuura; Yasuhiro Asahina; Mina Nakagawa; Mamoru Watanabe; Minoru Sakamoto; Shinya Maekawa; Katsushi Tokunaga; Masashi Mizokami; Namiki Izumi
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-7
Journal Detail:
Title:  Journal of medical virology     Volume:  -     ISSN:  1096-9071     ISO Abbreviation:  J. Med. Virol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7705876     Medline TA:  J Med Virol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013 Wiley Periodicals, Inc.
Affiliation:
Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
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