Interleukin (IL) 28B genetic polymorphism is significantly associated with the sustained virological response rate in patients with chronic hepatitis C treated with pegylated interferon-α (PEG-IFN) plus ri...Interleukin (IL) 28B genetic polymorphism is significantly associated with the sustained virological response rate in patients with chronic hepatitis C treated with pegylated interferon-α (PEG-IFN) plus ribavirin and with spontaneous hepatitis C virus clearance. However, a consensus on the relationship between IL28B genetic polymorphism and the favorable outcome of chronic hepatitis B virus infection defined by hepatitis B e antigen seroconversion, and/or hepatitis B surface antigen seroclearance in patients treated with interferon or PEG-IFN has not been reached. Several reports failed to show a positive association, while some studies demonstrated a positive association in certain subject settings. More prospective studies including large cohorts are needed to determine the possible association between IL28B genetic polymorphism and the outcome of interferon or PEG-IFN treatment for chronic hepatitis B.展开更多
Single nucleotide polymorphisms near the interleukin28B(IL-28B)gene have been identified as strong predictors of both spontaneous or Peg-interferon(Peg-IFN)and ribavirin(RBV)induced clearance of hepatitis C virus(HCV)...Single nucleotide polymorphisms near the interleukin28B(IL-28B)gene have been identified as strong predictors of both spontaneous or Peg-interferon(Peg-IFN)and ribavirin(RBV)induced clearance of hepatitis C virus(HCV).Several studies have shown that,in patients with genotype 1(GT-1),rs12979860 C/C and rs8099917T/T substitutions are associated with a more than twofold increase in sustained virological response rate to Peg-IFN and RBV treatment.Although new treatment regimens based on combination of DAA with or without IFN are in the approval phase,until combination regimens with a backbone of Peg-IFN will be used,we can expect that IL28B holds its importance.The clinical relevance of IL28B genotyping in treatment of patients infected with HCV genotype 2(GT-2)and 3(GT-3)remains controversial.Therefore,after a careful examination of the available literature,we analyzed the impact of IL28B in GT-2 and-3.Simple size of the studies and GT-2 and GT-3 proportion were discussed.An algorithm for the practical use of IL28B in these patients was suggested at the aim of optimizing treatment.展开更多
AIM:To analyze the role of rs12979860 and rs8099917polymorphisms in hepatitis C virus(HCV)genotype 1infection of Brazilians.METHODS:A total of 145 adult patients diagnosed with genotype 1 chronic hepatitis C(CHC)who h...AIM:To analyze the role of rs12979860 and rs8099917polymorphisms in hepatitis C virus(HCV)genotype 1infection of Brazilians.METHODS:A total of 145 adult patients diagnosed with genotype 1 chronic hepatitis C(CHC)who had completed a 48-wk regimen of pegylated-interferonα-2a or-2b plus ribavirin combination therapy were recruited from six large urban healthcare centers and199 healthy blood donors(controls)from a single site between January 2010 and January 2012.Data on the patients’response to treatment was collected.Polymerase chain reaction-restriction fragment length polymorphism genotyping of the interleukin(IL)28B gene fragment encompassing the single nucleotide polymorphisms(SNPs)rs12979860(C/T)and rs8099917(T/G)was carried out for 79 of the CHC patients and 199 of the controls.Bi-directional amplicon sequencing of the two SNPs was carried out for the remaining 66 CHC patients.RESULTS:SNP rs12979860 genotyping was successful in 99.5%of the controls and 97.2%of the CHC patients,whereas the SNP rs8099917 genotyping was successful in 95.5%of the controls and 100%of the CHC patients.The genotype and allele distributions for both rs12979860 and rs8099917 were significantly different between the control and CHC patient groups,with significantly higher genotype frequencies of CC and TT in the controls(P=0.037 and 0.046,respectively)and of TT and GG in the CHC patients(P=0.0009and 0.0001,respectively).Analysis of the CHC patients who achieved sustained virological response(SVR)to treatment(n=55)indicated that the rs12979860 C allele and CC genotype were predictors of SVR(P=0.02).No significant correlation was found between rs8099917 genotypes and treatment response,but carriers of the T allele showed significantly higher rates of SVR(P=0.02).Linkage disequilibrium analysis of the group that achieved SVR showed a significant association between rs12979860 and rs8099917(P=0.07).CONCLUSION:The higher allele frequency of rs12979860 C and rs8099917 T observed in non-HCVinfected individuals may indicate a potential protective role for these IL28B-related polymorphisms.展开更多
Background Genetic variations at the interleukin 28B （IL-28B） locus are important in predicting outcome following therapy for chronic hepatitis C virus （HCV） infection. The aim of this research was to evaluate the...Background Genetic variations at the interleukin 28B （IL-28B） locus are important in predicting outcome following therapy for chronic hepatitis C virus （HCV） infection. The aim of this research was to evaluate the role of IL-28B single nucleotide polymorphism （SNP） variations in Chinese patients undergoing pegylated interferon-a plus ribavirin （PEG-IFN-a/RBV） treatment. Methods To determine the effect of IL-28B variation on the response to HCV therapy, these variants were genotyped in a cohort of 220 patients who were chronically infected with HCV and received combined PEG-IFN-a/RBV therapy. Results The proportions of rs12979860 CC, CT, and TT genotypes were 71.4%, 25.0%, and 3.6% respectively, in the sustained virological response （SVR） group; 15.8%, 60.5%, and 23.7% respectively, in the null virological response （NVR） group; and 38.1%, 52.4%, and 9.5% respectively, in the relapse （Rel） group （P 〈0.05）. Logistic regression analysis showed that, compared to those having the CC genotype, CT heterozygotes had an increased risk of NVR and Rel （OR=10.95, 95% CI =4.12-29.11, P=1.5×10-7 and OR=3.93, 95% CI =1.86-8.32, P=-2.1×10-4 respectively）. The RNA quantification assay showed that patients with genotype CC exhibited much higher levels of IL-28 expression than those with genotype CT or TT （P 〈0.001）. Conclusions The IL-28B SNP rs12979860 genotype was related to the effectiveness of HCV therapy： patients with the CC rs12979860 genotype had higher rates of SVR than those with the CT or TT genotype, and the CC genotype revealed a significantly higher level of IL-28 mRNA expression.展开更多
The candidate polymorphism rs12979860 of interleukin 28B（IL28B） gene was genotyped by means of polymerase chain reaction（PCR） amplification and direct PCR sequencing, and then the role of this single nucleotide po...The candidate polymorphism rs12979860 of interleukin 28B（IL28B） gene was genotyped by means of polymerase chain reaction（PCR） amplification and direct PCR sequencing, and then the role of this single nucleotide polymorphism（SNP） in the response to the treatment of 172 Chinese patients with hepatitis C virus（HCV） chronic infection was analyzed. The results show that the frequencies of major homozygotes（CC） and heterozygotes（CT） of rs12979860 were 0.84 and 0.16, respectively, and the minor homozygotes（TT） wasn’t found in this cohort. A highly significant association was found between the CC genotype and sustained virological response（SVR） in HCV geno type 1 infected patients（P〈0.001） but not in HCV non-genotype 1 infected patients. In addition, a strong association was found between rs12979860 CC genotype and rapid virological response（RVR） in both HCV genotype 1 infected patients（P〈0.001） and non-genotype 1 infected patients（P〈0.001）. Taken together, these results indicate that IL28B polymorphism plays a key role in response to hepatitis C therapy in Chinese patients. Combine assessment of clinical predictors and the IL28B polymorphism may be beneficial to the individualized treatment decision in Asian chronic hepatitis C（CHC） patients.展开更多
文摘Interleukin (IL) 28B genetic polymorphism is significantly associated with the sustained virological response rate in patients with chronic hepatitis C treated with pegylated interferon-α (PEG-IFN) plus ribavirin and with spontaneous hepatitis C virus clearance. However, a consensus on the relationship between IL28B genetic polymorphism and the favorable outcome of chronic hepatitis B virus infection defined by hepatitis B e antigen seroconversion, and/or hepatitis B surface antigen seroclearance in patients treated with interferon or PEG-IFN has not been reached. Several reports failed to show a positive association, while some studies demonstrated a positive association in certain subject settings. More prospective studies including large cohorts are needed to determine the possible association between IL28B genetic polymorphism and the outcome of interferon or PEG-IFN treatment for chronic hepatitis B.
文摘Single nucleotide polymorphisms near the interleukin28B(IL-28B)gene have been identified as strong predictors of both spontaneous or Peg-interferon(Peg-IFN)and ribavirin(RBV)induced clearance of hepatitis C virus(HCV).Several studies have shown that,in patients with genotype 1(GT-1),rs12979860 C/C and rs8099917T/T substitutions are associated with a more than twofold increase in sustained virological response rate to Peg-IFN and RBV treatment.Although new treatment regimens based on combination of DAA with or without IFN are in the approval phase,until combination regimens with a backbone of Peg-IFN will be used,we can expect that IL28B holds its importance.The clinical relevance of IL28B genotyping in treatment of patients infected with HCV genotype 2(GT-2)and 3(GT-3)remains controversial.Therefore,after a careful examination of the available literature,we analyzed the impact of IL28B in GT-2 and-3.Simple size of the studies and GT-2 and GT-3 proportion were discussed.An algorithm for the practical use of IL28B in these patients was suggested at the aim of optimizing treatment.
基金Supported by Grants from the Research Fund from University of Region of Joinville,FAP-UNIVILLE
文摘AIM:To analyze the role of rs12979860 and rs8099917polymorphisms in hepatitis C virus(HCV)genotype 1infection of Brazilians.METHODS:A total of 145 adult patients diagnosed with genotype 1 chronic hepatitis C(CHC)who had completed a 48-wk regimen of pegylated-interferonα-2a or-2b plus ribavirin combination therapy were recruited from six large urban healthcare centers and199 healthy blood donors(controls)from a single site between January 2010 and January 2012.Data on the patients’response to treatment was collected.Polymerase chain reaction-restriction fragment length polymorphism genotyping of the interleukin(IL)28B gene fragment encompassing the single nucleotide polymorphisms(SNPs)rs12979860(C/T)and rs8099917(T/G)was carried out for 79 of the CHC patients and 199 of the controls.Bi-directional amplicon sequencing of the two SNPs was carried out for the remaining 66 CHC patients.RESULTS:SNP rs12979860 genotyping was successful in 99.5%of the controls and 97.2%of the CHC patients,whereas the SNP rs8099917 genotyping was successful in 95.5%of the controls and 100%of the CHC patients.The genotype and allele distributions for both rs12979860 and rs8099917 were significantly different between the control and CHC patient groups,with significantly higher genotype frequencies of CC and TT in the controls(P=0.037 and 0.046,respectively)and of TT and GG in the CHC patients(P=0.0009and 0.0001,respectively).Analysis of the CHC patients who achieved sustained virological response(SVR)to treatment(n=55)indicated that the rs12979860 C allele and CC genotype were predictors of SVR(P=0.02).No significant correlation was found between rs8099917 genotypes and treatment response,but carriers of the T allele showed significantly higher rates of SVR(P=0.02).Linkage disequilibrium analysis of the group that achieved SVR showed a significant association between rs12979860 and rs8099917(P=0.07).CONCLUSION:The higher allele frequency of rs12979860 C and rs8099917 T observed in non-HCVinfected individuals may indicate a potential protective role for these IL28B-related polymorphisms.
文摘Background Genetic variations at the interleukin 28B （IL-28B） locus are important in predicting outcome following therapy for chronic hepatitis C virus （HCV） infection. The aim of this research was to evaluate the role of IL-28B single nucleotide polymorphism （SNP） variations in Chinese patients undergoing pegylated interferon-a plus ribavirin （PEG-IFN-a/RBV） treatment. Methods To determine the effect of IL-28B variation on the response to HCV therapy, these variants were genotyped in a cohort of 220 patients who were chronically infected with HCV and received combined PEG-IFN-a/RBV therapy. Results The proportions of rs12979860 CC, CT, and TT genotypes were 71.4%, 25.0%, and 3.6% respectively, in the sustained virological response （SVR） group; 15.8%, 60.5%, and 23.7% respectively, in the null virological response （NVR） group; and 38.1%, 52.4%, and 9.5% respectively, in the relapse （Rel） group （P 〈0.05）. Logistic regression analysis showed that, compared to those having the CC genotype, CT heterozygotes had an increased risk of NVR and Rel （OR=10.95, 95% CI =4.12-29.11, P=1.5×10-7 and OR=3.93, 95% CI =1.86-8.32, P=-2.1×10-4 respectively）. The RNA quantification assay showed that patients with genotype CC exhibited much higher levels of IL-28 expression than those with genotype CT or TT （P 〈0.001）. Conclusions The IL-28B SNP rs12979860 genotype was related to the effectiveness of HCV therapy： patients with the CC rs12979860 genotype had higher rates of SVR than those with the CT or TT genotype, and the CC genotype revealed a significantly higher level of IL-28 mRNA expression.
基金Supported by the State Key Disciplines of Clinical Projects and the National Natural Science Foundation of China (No.30970415)
文摘The candidate polymorphism rs12979860 of interleukin 28B（IL28B） gene was genotyped by means of polymerase chain reaction（PCR） amplification and direct PCR sequencing, and then the role of this single nucleotide polymorphism（SNP） in the response to the treatment of 172 Chinese patients with hepatitis C virus（HCV） chronic infection was analyzed. The results show that the frequencies of major homozygotes（CC） and heterozygotes（CT） of rs12979860 were 0.84 and 0.16, respectively, and the minor homozygotes（TT） wasn’t found in this cohort. A highly significant association was found between the CC genotype and sustained virological response（SVR） in HCV geno type 1 infected patients（P〈0.001） but not in HCV non-genotype 1 infected patients. In addition, a strong association was found between rs12979860 CC genotype and rapid virological response（RVR） in both HCV genotype 1 infected patients（P〈0.001） and non-genotype 1 infected patients（P〈0.001）. Taken together, these results indicate that IL28B polymorphism plays a key role in response to hepatitis C therapy in Chinese patients. Combine assessment of clinical predictors and the IL28B polymorphism may be beneficial to the individualized treatment decision in Asian chronic hepatitis C（CHC） patients.
