title: Impact of IL28B-related single nucleotide polymorphisms on liver histopathology in chronic hepatitis C genotype 2 and 3.
abstract: OBJECTIVE
  Recently, several genome-wide association studies have revealed that single nucleotide polymorphisms (SNPs) in proximity to IL28B predict spontaneous clearance of HCV infection as well as outcome following peginterferon and ribavirin therapy among HCV genotype 1 infected patients. The present study aimed to evaluate the impact of IL28B SNP variability on liver histology in the context of a phase III treatment trial (NORDynamIC) for treatment-naïve patients with chronic HCV genotype 2 or 3 infection, where pretreatment liver biopsies were mandatory.
  
  
  METHODS
  Three hundred and thirty-nine Caucasian patients had samples available for IL28B genotyping (rs12979860) of whom 314 had pretreatment liver biopsies that were evaluated using the Ishak protocol, allowing for detailed grading and staging of liver histopathology.
  
  
  RESULTS
  IL28B CC(rs12979860) genotype in HCV genotype 3 infected patients was associated with higher ALT levels (p<0.0001), higher AST to platelet ratio index (APRI; p = 0.001), and higher baseline viral load (p<0.0001) as compared to patients with the CT or TT genotypes. Additionally the CC(rs12979860) genotype entailed more pronounced portal inflammation (p = 0.02) and steatosis (p = 0.03). None of these associations were noted among HCV genotype 2 infected patients.
  
  
  CONCLUSIONS
  This study shows that the CC(rs12979860) SNP is associated with more pronounced liver histopathology in patients chronically infected with HCV genotype 3, which may be secondary to higher viral load. The finding that IL28B variability did not impact on liver pathology or viral load among genotype 2 infected patients implies that IL28B may differentially regulate the course of genotype 2 and 3 infection.
authors.affiliation: Department of Infectious Diseases/Virology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Karolina
authors.initials: K
authors.lastname: Rembeck
authors.forename: Asa
authors.initials: A
authors.lastname: Alsiö
authors.forename: Peer Brehm
authors.initials: PB
authors.lastname: Christensen
authors.forename: Martti
authors.initials: M
authors.lastname: Färkkilä
authors.forename: Nina
authors.initials: N
authors.lastname: Langeland
authors.forename: Mads Rauning
authors.initials: MR
authors.lastname: Buhl
authors.forename: Court
authors.initials: C
authors.lastname: Pedersen
authors.forename: Kristine
authors.initials: K
authors.lastname: Mørch
authors.forename: Johan
authors.initials: J
authors.lastname: Westin
authors.forename: Magnus
authors.initials: M
authors.lastname: Lindh
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Hellstrand
authors.forename: Gunnar
authors.initials: G
authors.lastname: Norkrans
authors.forename: Martin
authors.initials: M
authors.lastname: Lagging
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D005234:Fatty Liver / Q000150:complications / Q000235:genetics / Q000821:virology; D005260:Female; D020022:Genetic Predisposition to Disease; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000821:virology*; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000473:pathology; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008099:Liver / Q000473:pathology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics; D019562:Viral Load / Q000235:genetics; D000095022:Interferon Lambda
chemical_list: D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D007372:Interferons; D007378:Interleukins; D012367:RNA, Viral; C000624353:interferon-lambda, human; D000095022:Interferon Lambda