AIM: To evaluate the implication of substitutions in the hepatitis C virus (HCV) non-structural 5A (NS5A) protein in the resistance of HCV during mono-interferon (IFN) or combined IFN-ribavirin (IFN-R) therapy. Althou...AIM: To evaluate the implication of substitutions in the hepatitis C virus (HCV) non-structural 5A (NS5A) protein in the resistance of HCV during mono-interferon (IFN) or combined IFN-ribavirin (IFN-R) therapy. Although NS5A has been reported to interact with the HCV RNA- dependent RNA polymerase, NS5B, as well as with many cellular proteins, the function of NS5A in the life cycle of HCV remains unclear. METHODS: HCV quasispecies were studied by clon- ing and sequencing of sequential isolates from patients infected by HCV genotype 1b. Patients were treated by IFN-α2b for 3 mo followed by IFN-α2b alone or com- bined IFN-R therapy for 9 additional months. Patients were categorized intro two groups based on their re- sponse to the treatments: 7 with sustained virological re- sponse (SVR) (quasispecies = 150) and 3 non-respond- ers (NR) to IFN-R (quasispecies = 106). RESULTS: Prior to treatment, SVR patients displayed a lower complexity of quasispecies than NR patients. Most patients had a decrease in the complexity of quasispe- cies during therapy. Analysis of amino acids substitu- tions showed that the degree of the complexity of the interferon sensitivity-determining region (ISDR) and the V3 domain of NS5A protein was able to discriminate thetwo groups of patients. Moreover, SVR patients displayed more variability in the NS5A region than NR patients. CONCLUSION: These results suggest that detailed mo- lecular analysis of the NS5A region may be important for understanding its function in IFN response during HCV 1b infection.展开更多
AIMTo evaluate the performance of FibroMeter<sup>Virus3G</sup>combined to the first generation tests aspartate aminotransferase-to-platelet ratio index(APRI)or Forns index to assess significant fibrosis in...AIMTo evaluate the performance of FibroMeter<sup>Virus3G</sup>combined to the first generation tests aspartate aminotransferase-to-platelet ratio index(APRI)or Forns index to assess significant fibrosis in chronic hepatitis C(CHC).METHODSFirst generation tests APRI or Forns were initially applied in a derivation population from Rio de Janeiro in Brazil considering cut-offs previously reported in the literature to evaluate significant fibrosis.FibroMeter<sup>Virus3G</sup>was sequentially applied to unclassified cases from APRI or Forns.Accuracy of non-invasive combination of tests,APRI plus FibroMeter<sup>Virus3G</sup>and Forns plus FibroMeter<sup>Virus3G</sup>was evaluated in the Brazilian derivation population.APRI plus FibroMeter<sup>Virus3G</sup>combination was validated in a population of CHC patients from Angers in France.All patients were submitted to liver biopsy staged according to METAVIR score by experienced hepatopathologists.Significant fibrosis was considered as METAVIR F≥2.The fibrosis stage classification was used as the reference for accuracy evaluation of non-invasive combination of tests.Blood samples for the calculation of serum tests were collected on the same day of biopsy procedure or within a maximum 3 mo interval and stored at-70°C.RESULTSSeven hundred and sixty CHC patients were included(222 in the derivation population and 538 in the validation group).In the derivation population,the FibroMeter<sup>Virus3G</sup>AUROC was similar to APRI AUROC(0.855 vs 0.815,P=0.06)but higher than Forns AUROC(0.769,P Virus3G</sup>cut-off to discriminate significant fibrosis was 0.61(80%diagnostic accuracy;75%in the validation population,P=0.134).The sequential combination of APRI or Forns with FibroMeter<sup>Virus3G</sup>in derivation population presented similar performance compared to FibroMeter<sup>Virus3G</sup>used alone(79%vs 78%vs 80%,respectively,P=0.791).Unclassified cases of significant fibrosis after applying APRI and Forns corresponded to 49%and 54%,respectively,of the total sample.However,the combination of APRI or Forns with FibroMeter<sup>Virus3G</sup>allowed 73%and 77%,respectively,of these unclassified cases to be correctly evaluated.Moreover,this combination resulted in a reduction of FibroMeter<sup>Virus3G</sup>requirement in approximately 50%of the entire sample.The stepwise combination of APRI and FibroMeter<sup>Virus3G</sup>applied to the validation population correctly identified 74%of patients with severe fibrosis(F≥3).CONCLUSIONThe stepwise combination of APRI or Forns with FibroMeter<sup>Virus3G</sup>may represent an accurate lower cost alternative when evaluating significant fibrosis,with no need for liver biopsy.展开更多
Background:With the rising global prevalence of fatty liver disease related to metabolic dysfunction,the association of this common liver condition with chronic kidney disease(CKD)has become increasingly evident.In 20...Background:With the rising global prevalence of fatty liver disease related to metabolic dysfunction,the association of this common liver condition with chronic kidney disease(CKD)has become increasingly evident.In 2020,the more inclusive term metabolic dysfunction-associated fatty liver disease(MAFLD)was proposed to replace the term non-alcoholic fatty liver disease(NAFLD).The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD.However,to date,there is no appropriate guidance on CKD in individuals with MAFLD.Furthermore,there has been little attention paid to the link between MAFLD and CKD in the Nephrology community.Methods and Results:Using a Delphi-based approach,a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and CKD.Conclusions:This Delphi-based consensus statement provided guidance on the epidemiology,mechanisms,management and treatment of MAFLD and CKD,as well as the relationship between the severity of MAFLD and risk of CKD,which establish a framework for the early prevention and management of these two common and interconnected diseases.展开更多
基金Supported by a grant from l’Agence National de la Recherche sur le Sida (ANRS grant 2001/011)
文摘AIM: To evaluate the implication of substitutions in the hepatitis C virus (HCV) non-structural 5A (NS5A) protein in the resistance of HCV during mono-interferon (IFN) or combined IFN-ribavirin (IFN-R) therapy. Although NS5A has been reported to interact with the HCV RNA- dependent RNA polymerase, NS5B, as well as with many cellular proteins, the function of NS5A in the life cycle of HCV remains unclear. METHODS: HCV quasispecies were studied by clon- ing and sequencing of sequential isolates from patients infected by HCV genotype 1b. Patients were treated by IFN-α2b for 3 mo followed by IFN-α2b alone or com- bined IFN-R therapy for 9 additional months. Patients were categorized intro two groups based on their re- sponse to the treatments: 7 with sustained virological re- sponse (SVR) (quasispecies = 150) and 3 non-respond- ers (NR) to IFN-R (quasispecies = 106). RESULTS: Prior to treatment, SVR patients displayed a lower complexity of quasispecies than NR patients. Most patients had a decrease in the complexity of quasispe- cies during therapy. Analysis of amino acids substitu- tions showed that the degree of the complexity of the interferon sensitivity-determining region (ISDR) and the V3 domain of NS5A protein was able to discriminate thetwo groups of patients. Moreover, SVR patients displayed more variability in the NS5A region than NR patients. CONCLUSION: These results suggest that detailed mo- lecular analysis of the NS5A region may be important for understanding its function in IFN response during HCV 1b infection.
文摘AIMTo evaluate the performance of FibroMeter<sup>Virus3G</sup>combined to the first generation tests aspartate aminotransferase-to-platelet ratio index(APRI)or Forns index to assess significant fibrosis in chronic hepatitis C(CHC).METHODSFirst generation tests APRI or Forns were initially applied in a derivation population from Rio de Janeiro in Brazil considering cut-offs previously reported in the literature to evaluate significant fibrosis.FibroMeter<sup>Virus3G</sup>was sequentially applied to unclassified cases from APRI or Forns.Accuracy of non-invasive combination of tests,APRI plus FibroMeter<sup>Virus3G</sup>and Forns plus FibroMeter<sup>Virus3G</sup>was evaluated in the Brazilian derivation population.APRI plus FibroMeter<sup>Virus3G</sup>combination was validated in a population of CHC patients from Angers in France.All patients were submitted to liver biopsy staged according to METAVIR score by experienced hepatopathologists.Significant fibrosis was considered as METAVIR F≥2.The fibrosis stage classification was used as the reference for accuracy evaluation of non-invasive combination of tests.Blood samples for the calculation of serum tests were collected on the same day of biopsy procedure or within a maximum 3 mo interval and stored at-70°C.RESULTSSeven hundred and sixty CHC patients were included(222 in the derivation population and 538 in the validation group).In the derivation population,the FibroMeter<sup>Virus3G</sup>AUROC was similar to APRI AUROC(0.855 vs 0.815,P=0.06)but higher than Forns AUROC(0.769,P Virus3G</sup>cut-off to discriminate significant fibrosis was 0.61(80%diagnostic accuracy;75%in the validation population,P=0.134).The sequential combination of APRI or Forns with FibroMeter<sup>Virus3G</sup>in derivation population presented similar performance compared to FibroMeter<sup>Virus3G</sup>used alone(79%vs 78%vs 80%,respectively,P=0.791).Unclassified cases of significant fibrosis after applying APRI and Forns corresponded to 49%and 54%,respectively,of the total sample.However,the combination of APRI or Forns with FibroMeter<sup>Virus3G</sup>allowed 73%and 77%,respectively,of these unclassified cases to be correctly evaluated.Moreover,this combination resulted in a reduction of FibroMeter<sup>Virus3G</sup>requirement in approximately 50%of the entire sample.The stepwise combination of APRI and FibroMeter<sup>Virus3G</sup>applied to the validation population correctly identified 74%of patients with severe fibrosis(F≥3).CONCLUSIONThe stepwise combination of APRI or Forns with FibroMeter<sup>Virus3G</sup>may represent an accurate lower cost alternative when evaluating significant fibrosis,with no need for liver biopsy.
文摘Background:With the rising global prevalence of fatty liver disease related to metabolic dysfunction,the association of this common liver condition with chronic kidney disease(CKD)has become increasingly evident.In 2020,the more inclusive term metabolic dysfunction-associated fatty liver disease(MAFLD)was proposed to replace the term non-alcoholic fatty liver disease(NAFLD).The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD.However,to date,there is no appropriate guidance on CKD in individuals with MAFLD.Furthermore,there has been little attention paid to the link between MAFLD and CKD in the Nephrology community.Methods and Results:Using a Delphi-based approach,a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and CKD.Conclusions:This Delphi-based consensus statement provided guidance on the epidemiology,mechanisms,management and treatment of MAFLD and CKD,as well as the relationship between the severity of MAFLD and risk of CKD,which establish a framework for the early prevention and management of these two common and interconnected diseases.
