title: Impact of IFNL4 rs12979860 and rs8099917 polymorphisms on response to Peg-Interferon-α and Ribavirin in patients with congenital bleeding disorder and chronic hepatitis C.
abstract: BACKGROUND
  The aim of this study was to determine whether two polymorphisms of the human interferon lambda 4 (IFNL4) gene (rs12979860 and rs8099917) can predict sustained virologic response (SVR) following antiviral therapy in patients with inherited bleeding disorder and chronic hepatitis C (CHC).
  
  
  METHODS
  This retrospective study was conducted on 294 patients with congenital bleeding disorder and CHC who were treated with Peg-Interferon-α (PegIFN) and Ribavirin (RBV). Baseline patient and viral parameters were measured and analyzed statistically to assess their combined and individual contributions to SVR prediction.
  
  
  RESULTS
  The most prevalent variants of rs12979860 and rs8099917 identified among the study patients were CT (45.9%) and TT (57.6%), respectively. Overall, SVR was achieved in 69% of the study patients. The rate of SVR was lower in patients with HCV genotype-1 than in those with HCV genotype-3 (62% vs 88%; P<.001; OR=0.23). Multivariate analysis of SVR predictors in patients with HCV genotype-1 infection included age (<24 years), BMI (<25), absence of cirrhosis, HCV RNA level (<400 000 IU/mL), rs8099917 TT and rs12979860 CC, all of which were associated with a higher SVR rate. In HCV genotype-3 infection, only rs12979860 CC was significantly associated with SVR.
  
  
  CONCLUSIONS
  These results demonstrate that polymorphisms of the IFNL4 gene are highly associated with SVR to PegIFN and RBV combination therapy in patients with a congenital bleeding disorder and CHC. Assessment of rs12979860 and rs8099917 genotypes can guide physicians in choosing an optimal treatment regimen, including less expensive therapies that may only be available in many geographic locales.
authors.affiliation: Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Keshvari
authors.affiliation: Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran.|Middle East Liver Diseases (MELD) Center, Tehran, Iran.
authors.forename: Seyed Moayed
authors.initials: SM
authors.lastname: Alavian
authors.affiliation: Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran.|Middle East Liver Diseases (MELD) Center, Tehran, Iran.
authors.forename: Bita
authors.initials: B
authors.lastname: Behnava
authors.affiliation: Armin Pathobiology Laboratory, Tehran, Iran.|Department of Biology, Arsanjan Branch, Islamic Azad University, Arsanjan, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Pouryasin
authors.affiliation: GATACA, LLC, Corporate Research Center, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Craig
authors.affiliation: Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran.|Middle East Liver Diseases (MELD) Center, Tehran, Iran.|Armin Pathobiology Laboratory, Tehran, Iran.
authors.forename: Heidar
authors.initials: H
authors.lastname: Sharafi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D002648:Child; D005260:Female; D056726:Genetic Association Studies; D006467:Hemophilia A / Q000150:complications*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use*; D000072230:Sustained Virologic Response; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; C579163:IFNL4 protein, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a
keywords: Pegylated-Interferon; chronic hepatitis C; hemophilia; rs12979860; rs8099917; sustained virologic response