title: An index to predict ribavirin-induced anemia in asian patients with chronic genotype 1 hepatitis C.
abstract: BACKGROUND
  Single-nucleotide polymorphisms (SNP) in the inosine triphosphate pyrophosphatase (ITPA) gene correlate with ribavirin (RBV)-induced anemia in patients with chronic hepatitis C (CHC) receiving combination therapy. Managing anemia is an early priority in the treatment process.
  
  
  OBJECTIVE
  The aim was to develop a predictive index based on ITPA SNP status to identify CHC patients at risk of anemia.
  
  
  METHODS
  A total of 418 eligible East Asian patients diagnosed with CHC genotype 1 (G1) received combination therapy in this study. Participant DNA was genotyped for a functional ITPA SNP (C/C, A/A or C/A) on chromosome 20 at rs1127354. A predictive index was constructed by incorporating independent factors identified for severe anemia events (hemoglobin < 10 g/dL). Areas under the receiver-operating characteristic curves (AUCs) represented the diagnostic accuracies of the predictive index in randomly assigned development and validation cohorts.
  
  
  RESULTS
  Multiple logistic regressions identified age (≥ 50 y: OR = 9.7, 95% CI = 5.0 - 18.6), ITPA rs1127354 (C/C: OR = 3.3, 95% CI = 1.8 - 5.8) and baseline hemoglobin (< 14.0 g/dL: OR 6.4, 95% CI = 3.3 - 12.1; 14.0 - 14.9: OR = 2.4, 95% CI = 1.2 - 4.6) as predictors of severe anemia throughout the treatment. For severe anemia, the predictive index incorporating age, ITPA SNP status and baseline hemoglobin yielded diagnostic accuracies (AUCs) of 0.830 (95% CI = 0.783 - 0.871) in the development (n = 324) and 0.902 (0.826 - 0.925) in the validation (n = 81) cohorts.
  
  
  CONCLUSIONS
  In patients with CHC G1 and receiving combination therapy, ITPA SNP-based index was an accurate and practical solution for prediction of severe anemia.
authors.affiliation: Institute of Clinical Medical Science, School of Medicine, China Medical University, Taichung, Taiwan ; School of Medicine, China Medical University, Taichung, Taiwan ; Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Sheng-Hung
authors.initials: SH
authors.lastname: Chen
authors.affiliation: School of Medicine, China Medical University, Taichung, Taiwan ; Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Cheng-Yuan
authors.initials: CY
authors.lastname: Peng
authors.affiliation: Institute of Clinical Medical Science, School of Medicine, China Medical University, Taichung, Taiwan ; Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan ; College of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Hsueh-Chou
authors.initials: HC
authors.lastname: Lai
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Wen-Pang
authors.initials: WP
authors.lastname: Su
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chia-Hsin
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Institute of Biostatistics, China Medical University, Taichung, Taiwan.
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Li
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Po-Heng
authors.initials: PH
authors.lastname: Chuang
authors.affiliation: Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Ching-Hsiang
authors.initials: CH
authors.lastname: Chen
keywords: Anemia; Hepatitis C; Inosine Triphosphate; Polymorphism; Ribavirin
references.citation: Eur J Gastroenterol Hepatol. 2012 Aug;24(8):890-6
references.pmid: 22584257
references.citation: World J Gastroenterol. 2012 Nov 7;18(41):5879-88
references.pmid: 23139603
references.citation: J Med Virol. 2012 Jul;84(7):1106-14
references.pmid: 22585729
references.citation: Antimicrob Agents Chemother. 2004 Oct;48(10 ):3813-6
references.pmid: 15388439
references.citation: J Virol Methods. 2012 Sep;184(1-2):103-5
references.pmid: 22613675
references.citation: Antimicrob Agents Chemother. 2012 Jun;56(6):2987-93
references.pmid: 22430973
references.citation: Gastroenterology. 2010 Nov;139(5):1602-11, 1611.e1
references.pmid: 20723545
references.citation: J Hepatol. 2012 Feb;56(2):313-9
references.pmid: 21703177
references.citation: J Hepatol. 2001 Jun;34(6):911-6
references.pmid: 11451176
references.citation: J Infect Dis. 2011 Jul 1;204(1):84-93
references.pmid: 21628662
references.citation: J Med Virol. 2011 Jun;83(6):1048-57
references.pmid: 21503919
references.citation: Gastroenterology. 2010 Oct;139(4):1190-7
references.pmid: 20637204
references.citation: Aliment Pharmacol Ther. 2002 Sep;16(9):1623-32
references.pmid: 12197841
references.citation: J Gastroenterol Hepatol. 2009 Mar;24(3):336-45
references.pmid: 19335784
references.citation: Antivir Ther. 2012;17(8):1581-92
references.pmid: 22809728
references.citation: Hepatol Res. 2006 Jan;34(1):23-7
references.pmid: 16325463
references.citation: Liver Int. 2006 Nov;26(9):1079-86
references.pmid: 17032408
references.citation: Cancer. 1950 Jan;3(1):32-5
references.pmid: 15405679
references.citation: Hepatol Res. 2010 Nov;40(11):1063-71
references.pmid: 20977565
references.citation: Kaohsiung J Med Sci. 2010 Sep;26(9):461-9
references.pmid: 20837342
references.citation: J Viral Hepat. 2012 Sep;19(9):635-9
references.pmid: 22863267
references.citation: Kaohsiung J Med Sci. 2012 Feb;28(2):86-93
references.pmid: 22313535
references.citation: J Viral Hepat. 2012 Jun;19(6):414-22
references.pmid: 22571903
references.citation: Hepatology. 2011 Feb;53(2):415-21
references.pmid: 21246582
references.citation: Liver Transpl. 2011 Nov;17 (11):1318-27
references.pmid: 21761553
references.citation: J Formos Med Assoc. 2007 Feb;106(2):148-55
references.pmid: 17339159
references.citation: J Med Virol. 2013 Mar;85(3):449-58
references.pmid: 23297176
references.citation: Ren Fail. 2012;34(4):429-34
references.pmid: 22264026
references.citation: Hepatology. 2015 Jan;61(1):408-9
references.pmid: 24752986
references.citation: J Viral Hepat. 2013 Apr;20(4):e124-6
references.pmid: 23490380
references.citation: Hepatology. 2011 Feb;53(2):389-95
references.pmid: 21274861
references.citation: J Hepatol. 2013 Nov;59(5):964-71
references.pmid: 23850877
references.citation: Antivir Ther. 2010;15(5):687-95
references.pmid: 20710050
references.citation: Hepatology. 2014 Jun;59(6):2131-9
references.pmid: 24519039
references.citation: Clin Microbiol Infect. 2011 Feb;17(2):107-15
references.pmid: 21091831
references.citation: J Infect Dis. 2012 Feb 1;205(3):376-83
references.pmid: 22158703
references.citation: Hepatology. 2011 Jan;53(1):7-13
references.pmid: 21254157
references.citation: Hepatology. 2014 Jun;59(6):2152-60
references.pmid: 24449403
references.citation: Hepatology. 2008 Jun;47(6):1884-93
references.pmid: 18508296