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Interleukin-28 and hepatitis C virus genotype-4:Treatment-induced clearance and liver fibrosis

查看全文 作  者:Moutaz [1,2]Derbala;Nasser [3]Rizk;Fatima [4]Shebl;Saad [1]Alkaabi;Nazeeh [1]Eldweik;Anil [1]John;Manik [1]Sharma;Rafie [1]Yaqoob;Muneera [1]Almohanadi;Mohammed [1]Butt;Khaled [1]Alejji 高影响力作者 机构地区:[1]Department of Gastroenterology and Hepatology,Hamad Hospital,Doha 3050,Qatar;[2]Department of Gastroenterology and Hepatology,Weill Cornell Medical College,Doha 3050,Qatar;[3]Department of Health Sciences,Qatar University,Doha 2713,Qatar;[4]Chronic Disease Epidemiology Division,Yale School of Public Health,New Haven,CT 06520,United States高影响力机构 出  处:《World Journal of Gastroenterology》索引2012年第18卷第47期,共6页高影响力期刊 基  金:Supported by Hamad Hospital-HMC and Qatar UniversityHealth Sciences-Biomedical Labs;sponsored by HMC 摘  要:AIM:To investigate the association between interleukin-28B(IL28B) genotype and response to treatment and hepatic fibrosis in patients with hepatitis C virus(HCV) genotype 4.METHODS:Two hundred and one HCV-genotype 4 patients were included.All patients were treated with Peginterferon alph2a/Ribavirin for 48 wk.End of treatment response(ETR) was defined as loss of detectable serum HCV RNA at the end of treatment.Sustained viral response(SVR) was defined as loss of detectable serum HCV RNA at the end of 24 wk follow up.Genotyping of IL28B rs12979860 was performed using the TaqMan assay.We used logistic regression to estimate the adjusted odds ratio(aOR) and 95%CI.RESULTS:The study included 201 HCV-genotype 4 patients.The majority of patients were men(89.6%),with a median age of 47 years,inter-quartile range(40-51).Approximately 62.5% of patients had ETR,and 49.6% had SVR.Individuals who achieved SVR were more likely to be younger(χ 2 = 4.91,P = 0.027),and less likely to have fibrosis(χ 2 = 15.54,P < 0.0001),or inflammation(χ 2 = 7.58,P = 0.006).The genotype distribution of rs12979860 was 36.2%,49.0% and 14.8% for genotypes CC,CT,and TT,respectively.In these participants,rs12979860 genotype distribution did not differ by gender(P = 0.466),pretreatment viral load(P = 0.600),inflammation(P = 0.435),or fibrosis(P = 0.291).The frequencies of IL28B rs12979860 genotypes were TT(14.8%),CT(49.0%),and CC(36.2%).Compared to rs12979860 genotype TT,aORs(95%CI) for ETR and SVR were:CC genotype,[17.55(5.34-57.69) and 5.92(2.09-16.76),respectively];CT genotype,[5.15(1.80-14.78) and 2.48(0.94-6.52),respectively].In the current study,the patients who did not achieve ETR or SVR had a lower prevalence of rs12979860 CC(17.4% and 23.3%,respectively) than individuals who had ETR or SVR(47.9% and 47.2%,respectively).Individuals with rs12979860 CC genotype had approximately 6 times the odds of SVR compared to individuals with TT genotype(aOR = 5.92;95%CI:2.09-16.76).Similarly,patients with CT genotype had SVR more often than patients with TT genotype(aOR = 2.48;95%CI:0.94-6.52).Carrying at least one copy of the C allele(genotypes CT and CC) had almost 8 times the probability of ETR compared to those with genotype rs12979860 TT(aOR = 7.87;95%CI:2.84-21.82),and approximately 3 times the odds of SVR compared to those with genotype rs12979860 TT(aOR = 3.46;95%CI:1.37-8.74).In addition,data were consistent with a significant gene-dose relationship(aOR = 4.05/allele;95%CI:2.27-7.22).The association between rs12979860 genotype and SVR was similar among those who achieved and those who did not achieve SVR.CONCLUSION:In HCV-genotype 4 patients,rs12979860 is a sensitive predictor of viral clearance,independent of viral load,age,gender or fibrosis,with no similar relation to severity of fibrosis. 关 键 词:丙型肝炎病毒 基因型频率 肝纤维化 白细胞介素 治疗 LOGISTIC 间隙 C型
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