{"title":"在埃及慢性丙型肝炎患者中,Chemerin是索非布韦、聚乙二醇化干扰素和利巴韦林预后不可缺少的治疗前预测因子","authors":"M. El-Derany","doi":"10.21608/ajps.2019.70245","DOIUrl":null,"url":null,"abstract":"Chronic hepatitis C (CHC) treatment modalities dramatically evolve, however some patients still suffer treatment failure with sever aggressive side effects. Accordingly personalizing antiviral treatment becomes an urgent cornerstone in treatment path. Inflammation is one of the hallmarks of viral infection. Besides it is one of the main factors interfering with drug response. Accordingly, this study focused on studying some inflammatory markers interfering with antiviral response in different CHC patients. A cohort of 157 genotype 4 (G4) Egyptian CHC patients treated with sofosbuvir (SOF), pegylated interferon-alpha-2a (Peg-IFNα-2a) plus ribavirin (RBV) were enrolled. Single nucleotide polymorphism (SNP) within chemerin gene (rs17173608) was analyzed by quantitative real-time PCR (qRT-PCR). Serum chemerin, serum IL-6 and serum alpha-fetoprotein (AFP) were analyzed by enzyme-linked immunosorbent assay (ELISA). Fibrosis grade, serum AFP, serum IL-6 and serum chemerin levels were found to be significant univariant predictors of SOF, Peg- IFNα-2a and RBV response at (p<0.01). Moreover, G/G Chemerin (rs17173608) genotype was also proved to be associated with treatment failure (OR=17.067- 95% CI =6.684-43.575- p<0.001) in Egyptian CHC G4 patients. Combining all predictors in Multiple stepwise regression analysis concluded that higher serum chemerin levels and G/G Chemerin rs17173608 genotype formulated the strongest predictive model with a significant prediction capacity expressed by area under the receiving operating curve (AUROC) 0.881(95% CI = 0.832–0.931) with specificity of 77.1%, sensitivity of 80.2% and accuracy of 78.9%. Chemerin is a vital pretreatment predictor of anti-HCV drug response as it accurately predicts SOF, Peg- IFNα-2a and RBV different outcomes in naive Egyptian CHC G4 patients.","PeriodicalId":7603,"journal":{"name":"Al-Azhar Journal of Pharmaceutical Sciences","volume":"86 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"CHEMERIN IS AN INDISPENSABLE PRE-TREATMENT PREDICTOR OF SOFOSBUVIR, PEGYLATED INTERFERON-ALPHA AND RIBAVIRIN OUTCOMES IN CHRONIC HEPATITIS C EGYPTIAN PATIENTS\",\"authors\":\"M. El-Derany\",\"doi\":\"10.21608/ajps.2019.70245\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Chronic hepatitis C (CHC) treatment modalities dramatically evolve, however some patients still suffer treatment failure with sever aggressive side effects. Accordingly personalizing antiviral treatment becomes an urgent cornerstone in treatment path. Inflammation is one of the hallmarks of viral infection. Besides it is one of the main factors interfering with drug response. Accordingly, this study focused on studying some inflammatory markers interfering with antiviral response in different CHC patients. A cohort of 157 genotype 4 (G4) Egyptian CHC patients treated with sofosbuvir (SOF), pegylated interferon-alpha-2a (Peg-IFNα-2a) plus ribavirin (RBV) were enrolled. Single nucleotide polymorphism (SNP) within chemerin gene (rs17173608) was analyzed by quantitative real-time PCR (qRT-PCR). Serum chemerin, serum IL-6 and serum alpha-fetoprotein (AFP) were analyzed by enzyme-linked immunosorbent assay (ELISA). Fibrosis grade, serum AFP, serum IL-6 and serum chemerin levels were found to be significant univariant predictors of SOF, Peg- IFNα-2a and RBV response at (p<0.01). Moreover, G/G Chemerin (rs17173608) genotype was also proved to be associated with treatment failure (OR=17.067- 95% CI =6.684-43.575- p<0.001) in Egyptian CHC G4 patients. Combining all predictors in Multiple stepwise regression analysis concluded that higher serum chemerin levels and G/G Chemerin rs17173608 genotype formulated the strongest predictive model with a significant prediction capacity expressed by area under the receiving operating curve (AUROC) 0.881(95% CI = 0.832–0.931) with specificity of 77.1%, sensitivity of 80.2% and accuracy of 78.9%. Chemerin is a vital pretreatment predictor of anti-HCV drug response as it accurately predicts SOF, Peg- IFNα-2a and RBV different outcomes in naive Egyptian CHC G4 patients.\",\"PeriodicalId\":7603,\"journal\":{\"name\":\"Al-Azhar Journal of Pharmaceutical Sciences\",\"volume\":\"86 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2019-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Al-Azhar Journal of Pharmaceutical Sciences\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.21608/ajps.2019.70245\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Al-Azhar Journal of Pharmaceutical Sciences","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.21608/ajps.2019.70245","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 1
摘要
慢性丙型肝炎(CHC)的治疗方式发生了巨大的变化,然而一些患者仍然遭受治疗失败和严重的侵袭性副作用。因此,个性化抗病毒治疗成为治疗路径中一个紧迫的基石。炎症是病毒感染的标志之一。此外,它也是影响药物反应的主要因素之一。因此,本研究的重点是研究不同CHC患者中干扰抗病毒反应的炎症标志物。157名基因型4 (G4)埃及CHC患者接受索非布韦(SOF)、聚乙二醇化干扰素α-2a (Peg-IFNα-2a)加利巴韦林(RBV)治疗。采用实时荧光定量PCR (qRT-PCR)分析趋化素基因rs17173608的单核苷酸多态性(SNP)。采用酶联免疫吸附试验(ELISA)检测血清趋化素(chemerin)、血清白细胞介素(IL-6)和甲胎蛋白(AFP)。纤维化分级、血清AFP、血清IL-6、血清趋化素水平是soff、Peg- IFNα-2a、RBV反应的单变量预测因子(p<0.01)。此外,G/G Chemerin (rs17173608)基因型也被证明与埃及CHC G4患者的治疗失败相关(OR=17.067- 95% CI =6.684-43.575- p<0.001)。多元逐步回归分析结果表明,较高的血清趋化素水平和G/G趋化素rs17173608基因型构成最强的预测模型,其预测能力为接受工作曲线下面积(AUROC) 0.881(95% CI = 0.832 ~ 0.931),特异性为77.1%,敏感性为80.2%,准确性为78.9%。Chemerin是抗hcv药物反应的重要预处理预测因子,因为它能准确预测埃及CHC G4患者SOF、Peg- IFNα-2a和RBV的不同结局。
CHEMERIN IS AN INDISPENSABLE PRE-TREATMENT PREDICTOR OF SOFOSBUVIR, PEGYLATED INTERFERON-ALPHA AND RIBAVIRIN OUTCOMES IN CHRONIC HEPATITIS C EGYPTIAN PATIENTS
Chronic hepatitis C (CHC) treatment modalities dramatically evolve, however some patients still suffer treatment failure with sever aggressive side effects. Accordingly personalizing antiviral treatment becomes an urgent cornerstone in treatment path. Inflammation is one of the hallmarks of viral infection. Besides it is one of the main factors interfering with drug response. Accordingly, this study focused on studying some inflammatory markers interfering with antiviral response in different CHC patients. A cohort of 157 genotype 4 (G4) Egyptian CHC patients treated with sofosbuvir (SOF), pegylated interferon-alpha-2a (Peg-IFNα-2a) plus ribavirin (RBV) were enrolled. Single nucleotide polymorphism (SNP) within chemerin gene (rs17173608) was analyzed by quantitative real-time PCR (qRT-PCR). Serum chemerin, serum IL-6 and serum alpha-fetoprotein (AFP) were analyzed by enzyme-linked immunosorbent assay (ELISA). Fibrosis grade, serum AFP, serum IL-6 and serum chemerin levels were found to be significant univariant predictors of SOF, Peg- IFNα-2a and RBV response at (p<0.01). Moreover, G/G Chemerin (rs17173608) genotype was also proved to be associated with treatment failure (OR=17.067- 95% CI =6.684-43.575- p<0.001) in Egyptian CHC G4 patients. Combining all predictors in Multiple stepwise regression analysis concluded that higher serum chemerin levels and G/G Chemerin rs17173608 genotype formulated the strongest predictive model with a significant prediction capacity expressed by area under the receiving operating curve (AUROC) 0.881(95% CI = 0.832–0.931) with specificity of 77.1%, sensitivity of 80.2% and accuracy of 78.9%. Chemerin is a vital pretreatment predictor of anti-HCV drug response as it accurately predicts SOF, Peg- IFNα-2a and RBV different outcomes in naive Egyptian CHC G4 patients.