摘要
AIM: To identify predictors of sustained virological response in hemodialysed patients treated by PEGinterferon α for chronic hepatitis C, genotype 1.METHODS: The sustained virological response(SVR) rate, IL28 B genotype, IFNL4 genotype, initial viral load(IVL) and other pretreatment variables in 39 endstage renal disease patients(ESRD) on maintenance haemodialysis(HD) infected with hepatitis C virus(HCV), genotype 1b, were compared with a control group of 109 patients with normal kidney function treated within the same period. All the patients were treatment nave and had well compensated liver disease. The ESRD patients received 135 μg of PEGylated interferon α-2a(Peg IFN-α) weekly and a reduced dose of ribavirin(RBV) was administered to 23/39 patients with an initial haemoglobin level > 10 g/d L. Control group patients were given standard doses of Peg IFN-α and RBV. SVR was assessed as HCV RNA negativity 24 wk post-treatment. A t-test or ANOVA were used for comparisons of the means and a χ2 testcompared the frequencies.Logistic regression was used to determine significant predictors of SVR.Cutoff values for continuous variables were obtained from Receiver Operating Characteristic analysis.RESULTS:The distribution of IL28B rs12979860 CC,CT and TT genotypes in the ESRD group was 28.2%,64.1%and 7.7%,respectively,and 19.3%,62.4%and18.3%in the controls.The IFNL4 genotype was in almost absolute linkage disequlibrium with IL28B.The proportion of patients with a low IVL(<600000 IU/m L)was significantly higher in the ESRD group than in the controls(28/39,71.8%vs 51/109,46.8%,P=0.009),as was the proportion of patients with low IVL in IL28B CC carriers compared with non-CC carriers in the ESRD group(10/11,90.9%vs 18/28,64.3%,P=0.0035).This difference was not found in the controls(7/22,31.8%vs 44/87,50.6%,P=0.9).The overall SVR rate was 64.1%(25/39)in the ESRD group and 50.5%(55/109)in the control group(P=0.19).11/11(100%)and 19/22(86.4%)IL28B CC patients achieved SVR in the ESRD and control groups,respectively.A statistically significant association between SVR and IL28B and IFNL4 variants was found in both groups.The ESRD patients who achieved SVR showed the lowest IVL[median 21000,interquartile range(IQR):6000-23000IU/m L],compared with ESRD individuals without SVR(1680000,IQR:481000-6880000,P=0.001),controls with SVR(387000,IQR:111000-1253000)and controls without SVR(905000,IQR:451000-3020000).In ESRD,an IVL<600000 IU/m L was strongly associated with SVR:24/28(85.7%)patients who achieved SVR had viraemia below this threshold.CONCLUSION:Haemodialysis decreases the viral load,especially in IL28B CC genotype carriers.A low IVL was the strongest predictor of SVR in ESRD patients identified in multivariate analysis.
AIM: To identify predictors of sustained virological response in hemodialysed patients treated by PEGinterferon α for chronic hepatitis C, genotype 1.METHODS: The sustained virological response(SVR) rate, IL28 B genotype, IFNL4 genotype, initial viral load(IVL) and other pretreatment variables in 39 endstage renal disease patients(ESRD) on maintenance haemodialysis(HD) infected with hepatitis C virus(HCV), genotype 1b, were compared with a control group of 109 patients with normal kidney function treated within the same period. All the patients were treatment nave and had well compensated liver disease. The ESRD patients received 135 μg of PEGylated interferon α-2a(Peg IFN-α) weekly and a reduced dose of ribavirin(RBV) was administered to 23/39 patients with an initial haemoglobin level > 10 g/d L. Control group patients were given standard doses of Peg IFN-α and RBV. SVR was assessed as HCV RNA negativity 24 wk post-treatment. A t-test or ANOVA were used for comparisons of the means and a χ2 testcompared the frequencies.Logistic regression was used to determine significant predictors of SVR.Cutoff values for continuous variables were obtained from Receiver Operating Characteristic analysis.RESULTS:The distribution of IL28B rs12979860 CC,CT and TT genotypes in the ESRD group was 28.2%,64.1%and 7.7%,respectively,and 19.3%,62.4%and18.3%in the controls.The IFNL4 genotype was in almost absolute linkage disequlibrium with IL28B.The proportion of patients with a low IVL(<600000 IU/m L)was significantly higher in the ESRD group than in the controls(28/39,71.8%vs 51/109,46.8%,P=0.009),as was the proportion of patients with low IVL in IL28B CC carriers compared with non-CC carriers in the ESRD group(10/11,90.9%vs 18/28,64.3%,P=0.0035).This difference was not found in the controls(7/22,31.8%vs 44/87,50.6%,P=0.9).The overall SVR rate was 64.1%(25/39)in the ESRD group and 50.5%(55/109)in the control group(P=0.19).11/11(100%)and 19/22(86.4%)IL28B CC patients achieved SVR in the ESRD and control groups,respectively.A statistically significant association between SVR and IL28B and IFNL4 variants was found in both groups.The ESRD patients who achieved SVR showed the lowest IVL[median 21000,interquartile range(IQR):6000-23000IU/m L],compared with ESRD individuals without SVR(1680000,IQR:481000-6880000,P=0.001),controls with SVR(387000,IQR:111000-1253000)and controls without SVR(905000,IQR:451000-3020000).In ESRD,an IVL<600000 IU/m L was strongly associated with SVR:24/28(85.7%)patients who achieved SVR had viraemia below this threshold.CONCLUSION:Haemodialysis decreases the viral load,especially in IL28B CC genotype carriers.A low IVL was the strongest predictor of SVR in ESRD patients identified in multivariate analysis.
基金
Supported by The Internal Grant Agency of Ministry of Health of the Czech Republic,No.NT/11235-5
