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 geno...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.展开更多
AIM:To investigate the contribution of ABCB4 mutations to pediatric idiopathic gallstone disease and the potential of hormonal contraceptives to prompt clinical manifestations of multidrug resistance protein 3 deficie...AIM:To investigate the contribution of ABCB4 mutations to pediatric idiopathic gallstone disease and the potential of hormonal contraceptives to prompt clinical manifestations of multidrug resistance protein 3 deficiency.METHODS:Mutational analysis of ABCB4,screening for copy number variations by multiplex ligation-dependent probe amplification,genotyping for low expression allele c.1331T>C of ABCB11 and genotyping for variation c.55G>C in ABCG8 previously associated with cholesterol gallstones in adults was performed in 35 pediatric subjects with idiopathic gallstones who fulfilled the clinical criteria for low phospholipid-associated cholelithiasis syndrome(LPAC,OMIM#600803)and in 5young females with suspected LPAC and their families(5 probands,15 additional family members).The probands came to medical attention for contraceptiveassociated intrahepatic cholestasis.RESULTS:A possibly pathogenic variant of ABCB4was found only in one of the 35 pediatric subjects with idiopathic cholesterol gallstones whereas 15 members of the studied 5 LPAC kindreds were confirmed and another one was highly suspected to carry predictably pathogenic mutations in ABCB4.Among these 16,however,none developed gallstones in childhood.In 5index patients,all young females carrying at least one pathogenic mutation in one allele of ABCB4,manifestation of LPAC as intrahepatic cholestasis with elevated serum activity of gamma-glutamyltransferase was induced by hormonal contraceptives.Variants ABCB11c.1331T>C and ABCG8 c.55G>C were not significantly overrepresented in the 35 examined patients with suspect LPAC.CONCLUSION:Clinical criteria for LPAC syndrome caused by mutations in ABCB4 cannot be applied topediatric patients with idiopathic gallstones.Sexual immaturity even prevents manifestation of LPAC.展开更多
基金Supported by The Internal Grant Agency of Ministry of Health of the Czech Republic,No.NT/11235-5
文摘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The project (Ministry of Health,Czech Republic) for development of research organization 00023001 (IKEM,Prague,Czech Republic) - Institutional support PRVOUK-P24/LF1/3 and MH CZ - DRO VFN64165 to Dvorakova L and Hrebicek M
文摘AIM:To investigate the contribution of ABCB4 mutations to pediatric idiopathic gallstone disease and the potential of hormonal contraceptives to prompt clinical manifestations of multidrug resistance protein 3 deficiency.METHODS:Mutational analysis of ABCB4,screening for copy number variations by multiplex ligation-dependent probe amplification,genotyping for low expression allele c.1331T>C of ABCB11 and genotyping for variation c.55G>C in ABCG8 previously associated with cholesterol gallstones in adults was performed in 35 pediatric subjects with idiopathic gallstones who fulfilled the clinical criteria for low phospholipid-associated cholelithiasis syndrome(LPAC,OMIM#600803)and in 5young females with suspected LPAC and their families(5 probands,15 additional family members).The probands came to medical attention for contraceptiveassociated intrahepatic cholestasis.RESULTS:A possibly pathogenic variant of ABCB4was found only in one of the 35 pediatric subjects with idiopathic cholesterol gallstones whereas 15 members of the studied 5 LPAC kindreds were confirmed and another one was highly suspected to carry predictably pathogenic mutations in ABCB4.Among these 16,however,none developed gallstones in childhood.In 5index patients,all young females carrying at least one pathogenic mutation in one allele of ABCB4,manifestation of LPAC as intrahepatic cholestasis with elevated serum activity of gamma-glutamyltransferase was induced by hormonal contraceptives.Variants ABCB11c.1331T>C and ABCG8 c.55G>C were not significantly overrepresented in the 35 examined patients with suspect LPAC.CONCLUSION:Clinical criteria for LPAC syndrome caused by mutations in ABCB4 cannot be applied topediatric patients with idiopathic gallstones.Sexual immaturity even prevents manifestation of LPAC.
