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Review

Pharmacogenetics of Ribavirin-Induced Anemia in Hcv Patients

, , , &
Pages 925-941 | Received 21 Jul 2015, Accepted 05 Apr 2016, Published online: 01 Jun 2016

References

  • Davis GL , Esteban-MurR , RustgiVet al. Interferon alfa-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C. International Hepatitis Interventional Therapy Group . N. Engl. J. Med.339 ( 21 ), 1493 – 1499 ( 1998 ).
  • Mchutchison JG , GordonSC , SchiffERet al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group . N. Engl. J. Med.339 ( 21 ), 1485 – 1492 ( 1998 ).
  • Mchutchison JG , MannsMP , LongoDL . Definition and management of anemia in patients infected with hepatitis C virus . Liver Int.26 ( 4 ), 389 – 398 ( 2006 ).
  • Bodenheimer HC Jr , LindsayKL , DavisGL , LewisJH , ThungSN , SeeffLB . Tolerance and efficacy of oral ribavirin treatment of chronic hepatitis C: a multicenter trial . Hepatology26 ( 2 ), 473 – 477 ( 1997 ).
  • European Association for Study of Liver (EASL) . EASL Recommendations on Treatment of Hepatitis C 2015 . J. Hepatol.63 ( 1 ), 199 – 236 ( 2015 ).
  • Karino T , OzekiI , HigeSet al. Telaprevir impairs renal function and increases blood ribavirin concentration during telaprevir/pegylated interferon/ribavirin therapy for chronic hepatitis C . J. Viral Hepat.21 ( 5 ), 341 – 347 ( 2014 ).
  • De Nicolò A , BoglioneL , CiancioAet al. Telaprevir-S isomer enhances ribavirin exposure and the ribavirin-related haemolytic anemia in a concentration-dependent manner . Antiviral Res.109 , 7 – 14 ( 2014 ).
  • Boglione L , De NicoloA , CusatoJ , CaritiG , Di PerriG , D'AvolioA . Significant early higher ribavirin plasma concentrations in patients receiving a triple therapy with pegylated interferon, ribavirin and telaprevir . J. Viral Hepat.21 ( 4 ), 260 – 263 ( 2014 ).
  • Tempestilli M , LionettiR , D'offiziGet al. Increased plasma concentration of ribavirin as a result of renal dysfunction in hepatitis C virus patients treated with telaprevir . Hepatology60 ( 3 ), 1109 – 1110 ( 2014 ).
  • Mauss S , HueppeD , AlshuthU . Renal impairment is frequent in chronic hepatitis C patients under triple therapy with telaprevir or boceprevir . Hepatology59 ( 1 ), 46 – 48 ( 2014 ).
  • Webster DP , KlenermanP , DusheikoGM . Hepatitis C . Lancet385 ( 9973 ), 1124 – 1135 ( 2015 ).
  • Koh C , LiangTJ . What is the future of ribavirin therapy for hepatitis C?Antiviral Res.104 , 34 – 39 ( 2014 ).
  • FDA . Clinical pharmacology and biopharmaceutics review(s) ( 1998 ). www.accessdata.fda.gov/drugsatfda_docs/nda/98/20903_INTRON%20A%20REBETOL_BIOPHARMR.PDF .
  • Moss AM , EndresCJ , Ruiz-GarciaA , ChoiDS , UnadkatJD . Role of the equilibrative and concentrative nucleoside transporters in the intestinal absorption of the nucleoside drug, ribavirin, in wild-type and Ent1(-/-) mice . Mol. Pharm.9 ( 9 ), 2442 – 2449 ( 2012 ).
  • Li L , KooSH , LimentaLMet al. Effect of dietary purines on the pharmacokinetics of orally administered ribavirin . J. Clin. Pharmacol.49 ( 6 ), 661 – 667 ( 2009 ).
  • Willis RC , CarsonDA , SeegmillerJE . Adenosine kinase initiates the major route of ribavirin activation in a cultured human cell line . Proc. Natl Acad. Sci. USA75 ( 7 ), 3042 – 3044 ( 1978 ).
  • Endres CJ , MossAM , KeBet al. The role of the equilibrative nucleoside transporter 1 (ENT1) in transport and metabolism of ribavirin by human and wild-type or Ent1-/- mouse erythrocytes . J. Pharmacol. Exp. Ther.329 ( 1 ), 387 – 398 ( 2009 ).
  • Wu JZ , LarsonG , HongZ . Dual-action mechanism of viramidine functioning as a prodrug and as a catabolic inhibitor for ribavirin . Antimicrob. Agents Chemother.48 ( 10 ), 4006 – 4008 ( 2004 ).
  • PubChem . www.pubchem.com .
  • Homma M , MatsuzakiY , InoueYet al. Marked elevation of erythrocyte ribavirin levels in interferon and ribavirin-induced anemia . Clin. Gastroenterol. Hepatol.2 ( 4 ), 337 – 339 ( 2004 ).
  • D'Avolio A , CiancioA , SiccardiMet al. Inosine triphosphatase polymorphisms and ribavirin pharmacokinetics as determinants of ribavirin-associate anemia in patients receiving standard anti-HCV treatment . Ther. Drug Monit.34 ( 2 ), 165 – 170 ( 2012 ).
  • Hitomi Y , CirulliET , FellayJet al. Inosine triphosphate protects against ribavirin-induced adenosine triphosphate loss by adenylosuccinate synthase function . Gastroenterology140 ( 4 ), 1314 – 1321 ( 2011 ).
  • De Franceschi L , FattovichG , TurriniFet al. Hemolytic anemia induced by ribavirin therapy in patients with chronic hepatitis C virus infection: role of membrane oxidative damage . Hepatology31 ( 4 ), 997 – 1004 ( 2000 ).
  • Page T , ConnorJD . The metabolism of ribavirin in erythrocytes and nucleated cells . Int. J. Biochem.22 ( 4 ), 379 – 383 ( 1990 ).
  • De Nicolò A , CusatoJ , BoglioneLet al. Early ribavirin plasma concentrations as predictor of anemia onset after one month of anti-HCV therapy in ITPA stratified population . Presented at : 14th International Workshop on Clinical Pharmacology of HIV Therapy . Amsterdam, The Netherlands , March 2013 .
  • Guo H , SunS , YangZ , TangX , WangY . Strategies for ribavirin prodrugs and delivery systems for reducing the side-effect hemolysis and enhancing their therapeutic effect . J. Control. Release209 , 27 – 36 ( 2015 ).
  • Agnesod D , De NicoloA , SimieleMet al. Development and validation of a useful UPLC-MS/MS method for quantification of total and phosphorylated-ribavirin in peripheral blood mononuclear cells of HCV+ patients . J. Pharm. Biomed. Anal.90 , 119 – 126 ( 2013 ).
  • D'Avolio A , De NicoloA , AgnesodDet al. A UPLC-MS/MS method for the simultaneous plasma quantification of all isomeric forms of the new anti-HCV protease inhibitors boceprevir and telaprevir . J. Pharm. Biomed. Anal.78–79 , 217 – 223 ( 2013 ).
  • D'Avolio A , De NicoloA , SimieleMet al. Development and validation of a useful HPLC-UV method for quantification of total and phosphorylated-ribavirin in blood and erythrocytes of HCV+ patients . J. Pharm. Biomed. Anal.66 , 376 – 380 ( 2012 ).
  • D'Avolio A , CusatoJ , CalcagnoA , Di PerriG . Estimating ribavirin plasma exposure: genetics or therapeutic drug monitoring?J. Hepatol.59 ( 3 ), 633 – 634 ( 2013 ).
  • D'Avolio A , CiancioA , SiccardiMet al. Ribavirin pharmacokinetics and interleukin 28B plus cytochrome P450 27B1 single-nucleotide polymorphisms as predictors of response to pegylated interferon/ribavirin treatment in patients infected with hepatitis C virus genotype 1/4 . Hepatology54 ( 6 ), 2278 – 2279 ( 2011 ).
  • Tsubota A , HiroseY , IzumiN , KumadaH . Pharmacokinetics of ribavirin in combined interferon-alpha 2b and ribavirin therapy for chronic hepatitis C virus infection . Br. J. Clin. Pharmacol.55 ( 4 ), 360 – 367 ( 2003 ).
  • Conti F , VukoticR , LorenziniSet al. Increase of ribavirin dose improves sustained virological response in HCV-genotype 1 patients with a partial response to peg-interferon and ribavirin . Ann. Hepatol.13 ( 2 ), 196 – 203 ( 2014 ).
  • D'Avolio A , CiancioA , SiccardiMet al. Negative predictive value of IL28B, SLC28A2, and CYP27B1 SNPs and low RBV plasma exposure for therapeutic response to PEG/IFN-RBV treatment . Ther. Drug Monit.34 ( 6 ), 722 – 728 ( 2012 ).
  • Kubota R , KomiyamaT , KumagaiNet al. Optimal erythrocyte ribavirin level to reduce the risk of anemia and obtain an early virological response in patients with chronic hepatitis C caused by genotype 1b infection . Hepat. Res. Treat.2010 , 495928 ( 2010 ).
  • Rower JE , MeissnerEG , JimmersonLCet al. Serum and cellular ribavirin pharmacokinetic and concentration–effect analysis in HCV patients receiving sofosbuvir plus ribavirin . J. Antimicrob. Chemother.70 ( 8 ), 2322 – 2329 ( 2015 ).
  • D'Avolio A , De NicoloA , CusatoJet al. Association of ITPA polymorphisms rs6051702/rs1127354 instead of rs7270101/rs1127354 as predictor of ribavirin-associated anemia in chronic hepatitis C treated patients . Antiviral Res.100 ( 1 ), 114 – 119 ( 2013 ).
  • Fellay J , ThompsonAJ , GeDet al. ITPA gene variants protect against anemia in patients treated for chronic hepatitis C . Nature464 ( 7287 ), 405 – 408 ( 2010 ).
  • Thompson AJ , FellayJ , PatelKet al. Variants in the ITPA gene protect against ribavirin-induced hemolytic anemia and decrease the need for ribavirin dose reduction . Gastroenterology139 ( 4 ), 1181 – 1189 ( 2010 ).
  • Sumi S , MarinakiAM , ArenasMet al. Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency . Hum. Genet.111 ( 4–5 ), 360 – 367 ( 2002 ).
  • Shipkova M , LorenzK , OellerichM , WielandE , Von AhsenN . Measurement of erythrocyte inosine triphosphate pyrophosphohydrolase (ITPA) activity by HPLC and correlation of ITPA genotype–phenotype in a Caucasian population . Clin. Chem.52 ( 2 ), 240 – 247 ( 2006 ).
  • Bierau J , LindhoutM , BakkerJA . Pharmacogenetic significance of inosine triphosphatase . Pharmacogenomics8 ( 9 ), 1221 – 1228 ( 2007 ).
  • Ochi H , MaekawaT , AbeHet al. ITPA polymorphism affects ribavirin-induced anemia and outcomes of therapy – a genome-wide study of Japanese HCV virus patients . Gastroenterology139 ( 4 ), 1190 – 1197 ( 2010 ).
  • Sakamoto N , TanakaY , NakagawaMet al. ITPA gene variant protects against anemia induced by pegylated interferon-alpha and ribavirin therapy for Japanese patients with chronic hepatitis C . Hepatol. Res.40 ( 11 ), 1063 – 1071 ( 2010 ).
  • Thompson AJ , SantoroR , PiazzollaVet al. Inosine triphosphatase genetic variants are protective against anemia during antiviral therapy for HCV2/3 but do not decrease dose reductions of RBV or increase SVR . Hepatology53 ( 2 ), 389 – 395 ( 2011 ).
  • Azakami T , HayesCN , SezakiHet al. Common genetic polymorphism of ITPA gene affects ribavirin-induced anemia and effect of peg-interferon plus ribavirin therapy . J. Med. Virol.83 ( 6 ), 1048 – 1057 ( 2011 ).
  • Kurosaki M , TanakaY , TanakaKet al. Relationship between polymorphisms of the inosine triphosphatase gene and anemia or outcome after treatment with pegylated interferon and ribavirin . Antivir. Ther.16 ( 5 ), 685 – 694 ( 2011 ).
  • Seto WK , TanakaY , LiuK , LaiCL , YuenMF . The Effects of IL-28B and ITPA polymorphisms on treatment of hepatitis C virus genotype 6 . Am. J. Gastroenterol.106 ( 5 ), 1007 – 1008 ( 2011 ).
  • Eskesen AN , MelumE , MoghaddamAet al. Genetic variants at the ITPA locus protect against ribavirin-induced hemolytic anemia and dose reduction in an HCV G2/G3 cohort . Eur. J. Gastroenterol. Hepatol.24 ( 8 ), 890 – 896 ( 2012 ).
  • Kobayashi T , HigeS , TerashitaKet al. Anemia and thrombocytosis induced by ribavirin monotherapy in patients with chronic hepatitis C . J. Gastroenterol.47 ( 11 ), 1228 – 1237 ( 2012 ).
  • Krishnan SM , DixitNM . A formula to estimate the optimal dosage of ribavirin for the treatment of chronic hepatitis C: influence of ITPA polymorphisms . Antivir. Ther.17 ( 8 ), 1581 – 1592 ( 2012 ).
  • Miyamura T , KandaT , NakamotoSet al. Roles of ITPA and IL28B genotypes in chronic hepatitis C patients treated with peginterferon plus ribavirin . Viruses4 ( 8 ), 1264 – 1278 ( 2012 ).
  • Motomura T , KogaE , TaketomiAet al. Efficacy of splenectomy in preventing anemia in patients with recurrent hepatitis C following liver transplantation is not dependent on inosine triphosphate pyrophosphatase genotype . Hepatol. Res.42 ( 3 ), 288 – 295 ( 2013 ).
  • Naggie S , RallonNI , BenitoJMet al. Variants in the ITPA gene protect against ribavirin-induced hemolytic anemia in HIV/HCV-coinfected patients with all HCV genotypes . J. Infect. Dis.205 ( 3 ), 376 – 383 ( 2012 ).
  • Nishimura T , OsakiR , ShioyaMet al. Polymorphism of the inosine triphosphate pyrophosphatase gene predicts ribavirin-induced anemia in chronic hepatitis C patients . Mol. Med. Rep.5 ( 2 ), 517 – 520 ( 2012 ).
  • Tsubota A , ShimadaN , AbeHet al. Several factors including ITPA polymorphism influence ribavirin-induced anemia in chronic hepatitis C . World J. Gastroenterol.18 ( 41 ), 5879 – 5888 ( 2012 ).
  • Rau M , StickelF , RussmannSet al. Impact of genetic SLC28 transporter and ITPA variants on ribavirin serum level, hemoglobin drop and therapeutic response in patients with HCV infection . J. Hepatol.58 ( 4 ), 669 – 675 ( 2012 ).
  • Ahmed WH , FurusyoN , ZakySet al. Pre-treatment role of inosine triphosphate pyrophosphatase polymorphism for predicting anemia in Egyptian hepatitis C virus patients . World J. Gastroenterol.19 ( 9 ), 1387 – 1395 ( 2013 ).
  • Clark PJ , AghemoA , DegasperiEet al. Inosine triphosphatase deficiency helps predict anemia, anemia management and response in chronic hepatitis C therapy . J. Viral Hepat.20 ( 12 ), 858 – 866 ( 2013 ).
  • Di Marco V , CalvarusoV , GrimaudoSet al. Role of IL-28B and inosine triphosphatase polymorphisms in efficacy and safety of Peg-Interferon and ribavirin in chronic hepatitis C compensated cirrhosis with and without oesophageal varices . J. Viral Hepat.20 ( 2 ), 113 – 121 ( 2013 ).
  • Fujino T , AoyagiY , TakahashiMet al. Association of ITPA polymorphism with outcomes of peginterferon-alpha plus ribavirin combination therapy . World J. Gastrointest. Pharmacol. Ther.4 ( 3 ), 54 – 60 ( 2013 ).
  • Kim JS , AhnSM , JungYKet al. The impact of inosine triphosphatase variants on hemoglobin level and sustained virologic response of chronic hepatitis C in Korean . J. Korean Med. Sci.28 ( 8 ), 1213 – 1219 ( 2013 ).
  • Kurosaki M , TanakaY , NishidaNet al. 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 . J. Med. Virol.85 ( 3 ), 449 – 458 ( 2013 ).
  • Scherzer TM , StattermayerAF , StauberRet al. Effect of gender and ITPA polymorphisms on ribavirin-induced anemia in chronic hepatitis C patients . J. Hepatol.59 ( 5 ), 964 – 971 ( 2013 ).
  • Seto WK , TsangOT , LiuKet al. Role of IL28B and inosine triphosphatase polymorphisms in the treatment of chronic hepatitis C virus genotype 6 infection . J. Viral Hepat.20 ( 7 ), 470 – 477 ( 2013 ).
  • Zhang XH , CaiQX , HongCX , LinCS , ZhaoZX . Prevalence of IL-28B and ITPA genotypes in Chinese Han population infected persistently with hepatitis C virus genotype 6 or HCV-1 . J. Med. Virol.85 ( 7 ), 1163 – 1169 ( 2013 ).
  • Matsuura K , TanakaY , WatanabeTet al. ITPA genetic variants influence efficacy of PEG-IFN/RBV therapy in older patients infected with HCV genotype 1 and favourable IL28B type . J. Viral Hepat.21 ( 7 ), 466 – 474 ( 2014 ).
  • Holmes JA , RobertsSK , AliRJet al. ITPA genotype protects against anemia during peginterferon and ribavirin therapy but does not influence virological response . Hepatology59 ( 6 ), 2152 – 2160 ( 2014 ).
  • Chen SH , PengCY , LaiHCet al. An index to predict ribavirin-induced anemia in asian patients with chronic genotype 1 hepatitis C . Hepat. Mon.15 ( 3 ), e27148 ( 2015 ).
  • Cusato J , AllegraS , BoglioneLet al. VDR gene polymorphisms impact on anemia at 2 weeks of anti-HCV therapy: a possible mechanism for early RBV-induced anemia . Pharmacogenet. Genomics25 ( 4 ), 164 – 172 ( 2015 ).
  • Hwang JJ , LoCC , LinCHet al. Association between IPTA gene polymorphisms and hematological abnormalities in hepatitis C virus-infected patients receiving combination therapy . Gut Liver9 ( 2 ), 214 – 223 ( 2015 ).
  • Peltenburg NC , BakkerJA , VroemenWHet al. Inosine triphosphate pyrophosphohydrolase activity: more accurate predictor for ribavirin-induced anemia in hepatitis C infected patients than ITPA genotype . Clin. Chem. Lab. Med.53 ( 12 ), 2021 – 2029 ( 2015 ).
  • Kucherenko A , PampukhaV , BobrovaI , MorozL , LivshitsL . ITPA gene variant may protect against anemia induced during pegylated interferon alfa and ribavirin combination treatment in Ukrainian patients with chronic hepatitis C . Tsitol. Genet.49 ( 2 ), 38 – 41 ( 2015 ).
  • Delvaux N , CostaVD , CostaMMet al. Inosine triphosphatase allele frequency and association with ribavirin-induced anemia in Brazilian patients receiving antiviral therapy for chronic hepatitis C . Mem. Inst. Oswaldo Cruz.110 ( 5 ), 636 – 643 ( 2015 ).
  • Zampino R , AlessioL , MarroneAet al. Role of ITPA and IL28B variants in the management of chronic hepatitis C treatment . Infez. Med.23 ( 2 ), 134 – 139 ( 2015 ).
  • Birerdinc A , EstepM , AfendyAet al. Gene expression profiles associated with anemia and ITPA genotypes in patients with chronic hepatitis C (CH-C) . J. Viral Hepat.19 ( 6 ), 414 – 422 ( 2012 ).
  • Rallon NI , MorelloJ , LabargaPet al. Impact of inosine triphosphatase gene variants on the risk of anemia in HIV/hepatitis C virus-coinfected patients treated for chronic hepatitis C . Clin. Infect. Dis.53 ( 12 ), 1291 – 1295 ( 2011 ).
  • Osinusi A , NaggieS , PooniaSet al. ITPA gene polymorphisms significantly affect hemoglobin decline and treatment outcomes in patients coinfected with HIV and HCV . J. Med. Virol.84 ( 7 ), 1106 – 1114 ( 2012 ).
  • Amanzada A , SchneiderS , MoriconiFet al. Early anemia and rapid virological response improve the predictive efficiency of IL28B-genotype for treatment outcome to antiviral combination therapy in patients infected with chronic HCV genotype 1 . J. Med. Virol.84 ( 8 ), 1208 – 1216 ( 2012 ).
  • Vidal F , Lopez-DuplaM , LagunoMet al. Pharmacogenetics of efficacy and safety of HCV treatment in HCV–HIV coinfected patients: significant associations with IL28B and SOCS3 gene variants . PLoS ONE7 ( 11 ), e47725 ( 2012 ).
  • Persico M , CapassoM , RussoRet al. Elevated expression and polymorphisms of SOCS3 influence patient response to antiviral therapy in chronic hepatitis C . Gut57 ( 4 ), 507 – 515 ( 2008 ).
  • Knapp S , YeeLJ , FrodshamAJet al. Polymorphisms in interferon-induced genes and the outcome of hepatitis C virus infection: roles of MxA, OAS-1 and PKR . Genes Immun.4 ( 6 ), 411 – 419 ( 2003 ).
  • Allegra S , CusatoJ , De NicoloAet al. Role of pharmacogenetic in ribavirin outcome prediction and pharmacokinetics in an Italian cohort of HCV-1 and 4 patients . Biomed. Pharmacother.69 , 47 – 55 ( 2015 ).
  • Lotsch J , HofmannWP , SchleckerCet al. Single and combined IL28B, ITPA and SLC28A3 host genetic markers modulating response to anti-hepatitis C therapy . Pharmacogenomics12 ( 12 ), 1729 – 1740 ( 2011 ).
  • Doehring A , HofmannWP , SchleckerCet al. Role of nucleoside transporters SLC28A2/3 and SLC29A1/2 genetics in ribavirin therapy: protection against anemia in patients with chronic hepatitis C . Pharmacogenet. Genomics21 ( 5 ), 289 – 296 ( 2011 ).
  • Kamal SM . Pharmacogenetics of hepatitis C: transition from interferon-based therapies to direct-acting antiviral agents . Hepat. Med.6 , 61 – 77 ( 2014 ).
  • Boglione L , De NicoloA , Di PerriG , D'AvolioA . Triple or dual therapy for HCV-1 naive patients? Optimizing selection tools . J. Hepatol.61 ( 1 ), 178 – 179 ( 2014 ).
  • Cusato J , AllegraS , De NicoloAet al. Intracellular accumulation of boceprevir according to plasma concentrations and pharmacogenetics . Int. J. Antimicrob. Agents45 ( 6 ), 657 – 661 ( 2015 ).
  • Cusato J , AllegraS , De NicoloAet al. ABCB11 and ABCB1 gene polymorphisms impact on telaprevir pharmacokinetic at one month of therapy . Biomed. Pharmacother.69 , 63 – 69 ( 2015 ).
  • Cusato J , AllegraS , De NicoloAet al. Intracellular and plasma trough concentration and pharmacogenetics of telaprevir . J. Pharm. Pharm. Sci.18 ( 2 ), 171 – 176 ( 2015 ).
  • Boglione L , De NicoloA , CardellinoCSet al. Relationship between the early boceprevir-S isomer plasma concentrations and the onset of breakthrough during HCV genotype 1 triple therapy . Clin. Microbiol. Infect.21 ( 2 ), 205 , e201–203 ( 2015 ).
  • Chayama K , HayesCN , AbeHet al. IL28B but not ITPA polymorphism is predictive of response to pegylated interferon, ribavirin, and telaprevir triple therapy in patients with genotype 1 hepatitis C . J. Infect. Dis.204 ( 1 ), 84 – 93 ( 2011 ).
  • Aghemo A , GrassiE , RumiMGet al. Limited utility of ITPA deficiency to predict early anemia in HCV patients with advanced fibrosis receiving telaprevir . PLoS ONE9 ( 4 ), e95881 ( 2014 ).
  • Ogawa E , FurusyoN , NakamutaMet al. Clinical milestones for the prediction of severe anemia by chronic hepatitis C patients receiving telaprevir-based triple therapy . J. Hepatol.59 ( 4 ), 667 – 674 ( 2013 ).
  • Ogawa E , FurusyoN , KajiwaraEet al. Comparative safety study on severe anemia by simeprevir- versus telaprevir-based triple therapy for chronic hepatitis C . J. Gastroenterol. Hepatol.30 ( 8 ), 1309 – 1316 ( 2015 ).
  • Ishida H , SakaneS , ToyamaTet al. Administration of low-dose epoetin-alpha facilitates adherence to ribavirin in triple therapy with pegylated interferon-alpha-2b and telaprevir . Hepatol. Res.44 ( 10 ), E84 – E91 ( 2014 ).
  • Milazzo L , PeriAM , MazzaliCet al. SLC29A1 polymorphism and prediction of anemia severity in patients with chronic hepatitis C receiving triple therapy with telaprevir . J. Antimicrob. Chemother.70 ( 4 ), 1155 – 1160 ( 2015 ).
  • Ampuero J , Del CampoJA , RojasLet al. Role of ITPA and SLC28A2 genes in the prediction of anemia associated with protease inhibitor plus ribavirin and peginterferon in hepatitis C treatment . J. Clin. Virol.68 , 56 – 60 ( 2015 ).
  • Von Essen MR , KongsbakM , SchjerlingP , OlgaardK , OdumN , GeislerC . Vitamin D controls T cell antigen receptor signaling and activation of human T cells . Nat. Immunol.11 ( 4 ), 344 – 349 ( 2010 ).
  • Arteh J , NarraS , NairS . Prevalence of vitamin D deficiency in chronic liver disease . Dig. Dis. Sci.55 ( 9 ), 2624 – 2628 ( 2010 ).
  • Chesney RW . Interactions of vitamin D and the proximal tubule . Pediatr. Nephrol.31 ( 1 ), 7 – 14 ( 2015 ).
  • Uitterlinden AG , FangY , Van MeursJB , PolsHA , Van LeeuwenJP . Genetics and biology of vitamin D receptor polymorphisms . Gene338 ( 2 ), 143 – 156 ( 2004 ).
  • Poon AH , GongL , Brasch-AndersenCet al. Very important pharmacogene summary for VDR . Pharmacogenet. Genomics22 ( 10 ), 758 – 763 ( 2012 ).
  • Wali RK , BaumCL , SitrinMD , BrasitusTA . 1,25(OH)2 vitamin D3 stimulates membrane phosphoinositide turnover, activates protein kinase C, and increases cytosolic calcium in rat colonic epithelium . J. Clin. Invest.85 ( 4 ), 1296 – 1303 ( 1990 ).
  • Tiffert T , LewVL . Elevated intracellular Ca2+ reveals a functional membrane nucleotide pool in intact human red blood cells . J. Gen. Physiol.138 ( 4 ), 381 – 391 ( 2011 ).
  • Strehler EE , CarideAJ , FiloteoAG , XiongY , PennistonJT , EnyediA . Plasma membrane Ca2+ ATPases as dynamic regulators of cellular calcium handling . Ann. NY Acad. Sci.1099 , 226 – 236 ( 2007 ).
  • FDA . Table of pharmacogenomic biomarkers in drug labeling ( 2015 ). www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm .
  • Boglione L , CusatoJ , AllegraS , CaritiG , Di PerriG , D'AvolioA . Role of IL28B genotyping in patients with hepatitis C virus-associated mixed cryoglobulinemia and response to PEG-IFN and ribavirin treatment . Arch. Virol.160 ( 8 ), 2009 – 2017 ( 2015 ).
  • Boglione L , CusatoJ , De NicoloAet al. Identification of naive HVC-4 patients who may be treated with pegylated-interferon and ribavirin according to IL28B polymorphisms . Antiviral Res.106 , 105 – 110 ( 2014 ).
  • Ge D , FellayJ , ThompsonAJet al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance . Nature461 ( 7262 ), 399 – 401 ( 2009 ).
  • Tanaka Y , NishidaN , SugiyamaMet al. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C . Nat. Genet.41 ( 10 ), 1105 – 1109 ( 2009 ).
  • Fried MW , ShiffmanML , ReddyKRet al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection . N. Engl. J. Med.347 ( 13 ), 975 – 982 ( 2002 ).
  • Kawaguchi-Suzuki M , FryeRF . The role of pharmacogenetics in the treatment of chronic hepatitis C infection . Pharmacotherapy34 ( 2 ), 185 – 201 ( 2014 ).
  • Cusato J , AllegraS , BoglioneLet al. Vitamin D pathway gene variants and HCV-2/3 therapy outcomes . Antivir. Ther.20 ( 3 ), 335 – 341 ( 2014 ).

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