title: IL28B is associated with outcomes of chronic HBV infection.
abstract: OBJECTIVE
  The role of IL28B gene variants and expression in hepatitis B virus (HBV) infections are not well understood. Here, we evaluated whether IL28B gene expression and rs12979860 variations are associated with HBV outcomes.
  
  
  METHODS
  IL28B genetic variations (rs12979860) were genotyped by pyrosequencing of DNA samples from 137 individuals with chronic HBV infection [50 inactive carriers (IC), 34 chronic hepatitis B (CHB), 27 cirrhosis, 26 hepatocellular carcinoma (HCC)], and 19 healthy controls. IL28A/B mRNA expression in peripheral blood mononuclear cells was determined by qRT-PCR, and serum IL28B protein was measured by ELISA.
  
  
  RESULTS
  Patients with IL28B C/C genotype had greater IL28A/B mRNA expression and higher IL28B protein levels than C/T patients. Within the various disease stages, compared to IC and healthy controls, IL28B expression was reduced in the CHB, cirrhosis, and HCC cohorts (CHB vs. IC, p=0.02; cirrhosis vs. IC, p=0.01; HCC vs. IC, p=0.001; CHB vs. controls, p<0.01; cirrhosis vs. controls, p<0.01; HCC vs. controls, p<0.01). When stratified with respect to serum HBV markers in the IC and CHB cohorts, IL28B mRNA and protein levels were higher in HBeAg-positive than negative individuals (p=0.01). Logistic regression analysis revealed that factors associated with high IL28B protein levels were C/C versus C/T genotype [p=0.016, odds ratio (OR)=0.25, 95% confidence interval (CI)=0.08-0.78], high alanine aminotransferase values (p<0.001, OR=8.02, 95% CI=2.64-24.4), and the IC stage of HBV infection (p<0.001).
  
  
  CONCLUSIONS
  Our data suggest that IL28B genetic variations may play an important role in long-term development of disease in chronic HBV infections.
authors.affiliation: Department of Hepatology, First Hospital of Jilin University, Changchun, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Hepatology, First Hospital of Jilin University, Changchun, China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Chi
authors.affiliation: Department of Hepatology, First Hospital of Jilin University, Changchun, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Hepatology, First Hospital of Jilin University, Changchun, China.
authors.forename: Yanhang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Hepatology, First Hospital of Jilin University, Changchun, China.
authors.forename: Wanyu
authors.initials: W
authors.lastname: Li
authors.affiliation: Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yang
authors.affiliation: Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Institute of Infection, Immunity and Inflamm, University of Glasgow, Glasgow, UK.
authors.forename: Damo
authors.initials: D
authors.lastname: Xu
authors.affiliation: Section of Hepatology, University of Manitoba, Winnipeg, Canada.
authors.forename: Manna
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Section of Hepatology, University of Manitoba, Winnipeg, Canada.
authors.forename: Gerald
authors.initials: G
authors.lastname: Minuk
authors.affiliation: Department of Clinical Epidemiology, First Hospital of Jilin University, Changchun, China. jiangjing19702000@yahoo.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Hepatology, First Hospital of Jilin University, Changchun, China. junqiniu2013@aliyun.com.
authors.forename: Junqi
authors.initials: J
authors.lastname: Niu
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D044466:Asian People / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D004279:DNA, Viral / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000208:ethnology / Q000235:genetics* / Q000276:immunology / Q000821:virology*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D007963:Leukocytes, Mononuclear; D008103:Liver Cirrhosis / Q000097:blood; D008113:Liver Neoplasms / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000095022:Interferon Lambda
chemical_list: D000410:Alanine Transaminase; D015415:Biomarkers; D004279:DNA, Viral; D007372:Interferons; D007378:Interleukins; D012333:RNA, Messenger; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: Hepatitis B virus; cirrhosis; genetic variation; hepatocellular carcinoma; interleukin 28B
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