title: Performance and Value of IFN-Lambda3 and IFN-Lambda4 Genotyping in Patients with Chronic Hepatitis C (CHC) Genotype 2/3 in a Real World Setting.
abstract: BACKGROUND
  SNPs near the interferon lambda (IFNL) 3 gene are predictors for sustained virological response (SVR) in patients with chronic hepatitis C genotype (GT) 1. In addition, a dinucleotide frame shift in ss469415590 was described, which generates IFNL4. In this study, we compared the role of IFNL4 variants with IFNL3-(rs12979860) and IFNL3-(rs8099917) on response to pegylated (PEG)-IFN and Ribavirin (RBV) in patients with chronic hepatitis C GT2/3.
  
  
  METHODS
  We recruited 1006 patients with chronic hepatitis C and GT2/3 in a large German registry. A treatment with PEG-IFN and Ribavirin was started by 959 patients. We performed genotyping of IFNL3 (rs12979860, n = 726; rs8099917, n = 687) and of IFNL4 (ss469415590; n = 631).
  
  
  RESULTS
  Both preferable IFNL3 genotypes were associated with RVR (both p<0.0001) rather than with SVR (rs12979860: p = 0.251; rs8099917: p = 0.447). Only RVR was linked to SVR in univariate and multivariate analyzes (both p<0.001). Concordance of genotyping in patients with available serum samples and EDTA blood samples (n = 259) was more than 96% for both IFNL3 SNPs. IFNL3-(rs12979860) correlated with IFNL4: 99.2% of patients with IFNL3-(rs12979860)-CC were IFNL4-(ss469415590)-TT/TT. IFNL3-(rs12979860)-CT was linked with IFNL4-(ss469415590)-TT/ΔG (98.0%) and IFNL3-(rs12979860)-TT was associated with IFNL4-(ss469415590)-ΔG/ΔG (97.6%).
  
  
  CONCLUSIONS
  IFNL3 genotyping from serum was highly efficient and can be used as an alternative if EDTA whole blood is not available. In Caucasian GT2/3 patients genotyping for INFL4-(ss469415590) does not lead to additional information for the decision-making process. Importantly, IFNL3 SNPs were not associated with SVR but with RVR. Even in the era of new direct acting antiviral (DAA) therapies, IFNL3 testing may therefore still be considered for naïve GT2/3 patients to decide if dual Peg-IFN/RBV therapy is an option in resource limited regions.
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.|German Liver Foundation, HepNet Study-House, Hannover and Frankfurt, Germany.|German Center for Infectious Diesease (DZIF), Hannover-Braunschweig, Germany.
authors.forename: Steffen B
authors.initials: SB
authors.lastname: Wiegand
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.|German Liver Foundation, HepNet Study-House, Hannover and Frankfurt, Germany.|German Center for Infectious Diesease (DZIF), Hannover-Braunschweig, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Heidrich
authors.affiliation: Department of Internal Medicine I, University of Frankfurt, Frankfurt, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Susser
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Rogalska-Taranta
authors.affiliation: IFI Institute for Interdisciplinary Medicine, Asklepios Klinik St Georg, Hamburg, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Petersen
authors.affiliation: Medical Practice, Hannover, Germany.
authors.forename: Klaus H W
authors.initials: KH
authors.lastname: Böker
authors.affiliation: Department of Internal Medicine II, University of Saarland, Saarland, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Grigorian
authors.affiliation: Department of Internal Medicine, Clinic for Internal Medicine St. Josefs hospital, Offenburg, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Link
authors.affiliation: Center for Addiction-Medicine, Hepatology and HIV, Praxiszentrum Kaiserdamm, Berlin, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Naumann
authors.affiliation: Medical Practice, Berlin, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: John
authors.affiliation: Department of Internal Medicine, University of Hamburg, Hamburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lueth
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, University of Magdeburg, Magdeburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Malfertheiner
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.|German Liver Foundation, HepNet Study-House, Hannover and Frankfurt, Germany.|German Center for Infectious Diesease (DZIF), Hannover-Braunschweig, Germany.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.|German Liver Foundation, HepNet Study-House, Hannover and Frankfurt, Germany.|German Center for Infectious Diesease (DZIF), Hannover-Braunschweig, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
authors.affiliation: German Liver Foundation, HepNet Study-House, Hannover and Frankfurt, Germany.|Department of Internal Medicine I, University of Frankfurt, Frankfurt, Germany.|German Center for Infectious Diesease (DZIF), Hannover-Braunschweig, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.|German Liver Foundation, HepNet Study-House, Hannover and Frankfurt, Germany.|German Center for Infectious Diesease (DZIF), Hannover-Braunschweig, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Cornberg
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000097:blood / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D019562:Viral Load / Q000235:genetics*; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C579163:IFNL4 protein, human