Il28B Cc-Genotype Association with Hla-Dqb1*0301 Allele Increases the Prediction of Spontaneous HCV RNA Clearance in Thalassaemic HCV-Infected Patients
Free accessResearch articleFirst published online November, 2011
Il28B Cc-Genotype Association with Hla-Dqb1*0301 Allele Increases the Prediction of Spontaneous HCV RNA Clearance in Thalassaemic HCV-Infected Patients
A single nucleotide polymorphism (SNP), upstream of the IL28B gene has been recently associated with natural clearance of HCV. In a well-characterized cohort of patients with thalassaemia major exposed to the risk of acquiring HCV infection by blood transfusions, we aimed to replicate this finding and to evaluate whether combining the IL28B genotype and HLA class II alleles allow viral clearance to be accurately predicted.
Methods
Of 168 patients, 130 with complete clinical history were included in the analysis. According with their HCV antibodies status 13 were defined HCV resistant, and 117 infected. Infected patients were subdivided, giving 49 with self-limiting and 68 with ongoing infection.
Results
IL28B CC-genotype was observed in 32 patients with self-limiting and in 23 with ongoing infection (64% versus 34%; P=0.004). HLA DQB1*0301 allele was associated with viral clearance in 36 cases (73%; P<0.0001). Both DQB1*0301 and IL28B CC-genotype were found to be independent predictors of HCV clearance (OR=5.64, 95% CI 1.52–20.9 and OR=5.76, 95% CI 2.16–15.33, respectively). With the addition of DQB1*0301, the accuracy of the prediction increased from 63% to 69%.
Conclusions
In addition to IL28B CC-genotype, HLA DQB1*0301 helps in predicting natural clearance of HCV after acute infection.
References
1.
Global surveillance and control of hepatitis C: report of a WHO consultation organized in collaboration with the Viral Hepatitis Prevention Board. J Viral Hepat1999; 6: 35–47.
2.
JaeckelE., CornbergM., WedemeyerH.Treatment of acute hepatitis C with interferon alfa-2b. N Engl J Med2001; 345: 1452–1457.
3.
DintsiosC.M., HaverkampA., WiegandJ.Economic evaluation of early monotherapy versus delayed monotherapy or combination therapy in patients with acute hepatitis C in Germany. Eur J Gastroenterol Hepatol2010; 22: 278–288.
4.
ThomasD.L., AstemborskiJ., RaiR.M.The natural history of hepatitis C virus infection: host, viral and environmental factors. JAMA2000; 284: 450–456.
5.
GrebelyJ., RaffaJ.D., LaiC.Factors associated with spontaneous clearance of hepatitis C virus among illicit drug users. Can J Gastroenterol2007; 21: 447–451.
6.
GerlachJ.T., DiepolderH.M., ZachovalR.Acute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance. Gastroenterology2003; 125: 80–88.
7.
YeeL.J.Host genetic determinants in hepatitis C virus infection. Genes Immun2004; 5: 237–245.
8.
ThurszM., YallopR., GoldinR.Influence of MHC class II genotype on outcome of infection with hepatitis C virus. The HENCORE group. Hepatitis C European Network for Cooperative Research. Lancet1999; 354: 2119–2124.
9.
DonaldsonP.T.The interrelationship between hepatitis C virus and HLA. Eur J Clin Invest1999; 29: 280–283.
10.
AsselahT., BiècheI., ParadisV.Genetics, genomics and proteomics: implications for the diagnosis and the treatment of chronic hepatitis C. Semin Liver Dis2007; 27: 13–27.
11.
AlricL., FortM., IzopetJ.Genes of the major histocompatibility complex class II influence the outcome of hepatitis C virus infection. Gastroenterology1997; 113: 1675–8.
12.
TibbsC., DonaldsonP., UnderhillJ.Evidence that the HLA DQA1*03 alleles confers protection from chronic HCV infection in Northen European Caucasoids. Hepatology1996; 24: 1342–1345.
13.
ThomasD.L., ThioC.L., MartinM.P.Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature2009; 461: 798–801.
14.
ScheuerP.J.Classification of chronic viral hepatitis: a need for reassessment. J Hepatol1991; 13: 372–374.
15.
GeD., FellayJ., ThompsonA.J.Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature2009; 461: 399–401.
16.
MangiaA., ThompsonA.J., SantoroR.Interleukin-28B polymorphism determines treatment response of patients with hepatitis C genotypes 2 and 3 who do not achieve a rapid virologic response. Gastroenterology2010; 139: 821–827.e1.
17.
MangiaA., GentileR., CascavillaI.HLA class II favors clearance of HCV infection and progression of the chronic liver damage. J Hepatol1999; 30: 984–989.
18.
ClarkP.J., ThompsonA.J., McHutchisonJ.G.IL28B genomic-based treatment paradigms for patients with chronic hepatitis C infection: the future of personalized HCV therapies. Am J Gastroenterol2011; 106: 38–45.
19.
HongX., YuR.B., SunN.X.Human leukocyte antigen class II DQB1*0301, DRB1*1101 alleles and spontaneous clearance of hepatitis C virus infection: a meta-analysis. World J Gastroenterol2005; 11: 7302–7307.
20.
WieseM., GrüngreiffK., GüthoffW.Outcome in hepatitis C (genotype 1b) single source outbreak in Germany a 25-year multicenter study. J Hepatol2005; 43: 590–598.
21.
ThioC.L.Host genetic factors and antiviral immune responses to HCV. Clin Liver Dis2008; 12: 713–726.
22.
TillmannH.L., ThompsonA.J., PatelK.A polymorphism near IL28B is associated with spontaneous clearance of acute hepatitis C virus and jaundice. Gastroenterology2010; 139: 1586–1592.e1.
23.
BakrI., RekacewiczC., El HosseinyM.Higher clearance of hepatitis C virus infection in females compared with males. Gut2006; 55: 1183–1187.
24.
RauchA., KutalikZ., DescombesP.Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome wide association study. Gastroenterology2010; 138: 1338–1345.e7.
25.
CongiaM., ClementeM.G., DessiC.HLA class II genes in chronic hepatitis C virus-infection and associated immunological disorders. Hepatology1996; 24: 1338–1341.
26.
TakakiA., WieseM., MaertensG.Cellular immune responses persist and humoral responses decrease two decades after recovery from a single-source outbreak of hepatitis C. Nat Med2000; 6: 578–582.
27.
MangiaA., CascavillaI., LezziG.HCV genotypes in patients with liver disease of different stage of severity. J Hepatol1997; 26: 1173–1178.
