Hepatitis C virus (HCV) is a serious public health problem affecting 170 million carriers worldwide. It is a leading cause of chronic hepatitis, cirrhosis, and liver cancer and is the primary cause for liver transplan...Hepatitis C virus (HCV) is a serious public health problem affecting 170 million carriers worldwide. It is a leading cause of chronic hepatitis, cirrhosis, and liver cancer and is the primary cause for liver transplantation worldwide. HCV genotype 6 (HCV-6) is restricted to South China, South-East Asia, and it is also occasionally found in migrant patients from endemic countries. HCV-6 has considerable genetic diversity with 23 subtypes (a to w). Although direct sequencing followed by phylogenetic analysis is the gold standard for HCV-6 genotyping and subtyping, there are also now rapid genotyping tests available such as the reverse hybridization line probe assay (INNO-LiPA II; Innogenetics, Zwijnaarde, Belgium). HCV-6 patients present with similar clinical manifestations as patients infected with other genotypes. Based on current evidence, the optimal treatment duration of HCV-6 with pegylated interferon/ribavirin should be 48 wk, although a shortened treatment duration of 24 wk could be sufficient in patients with low pretreatment viral load who achieve rapid virological response. In addition, the development of direct-acting antiviral agents is ongoing, and they give high response rate when combined with standard therapy. Herein, we review the epidemiology, classification, diagnosis and treatment as it pertain to HCV-6.展开更多
AIM: To investigate the early viral kinetics and interleukin-28B (IL28B) polymorphisms of hepatitis C genotype 6 during pegylated interferon and ribavirin therapy.
Rationale:Hepatitis C in the pediatric population is a large health burden globally.With its diverse genotypes as well as genotypic subtypes,there is a discrepancy in the genotypes used in research compared to their p...Rationale:Hepatitis C in the pediatric population is a large health burden globally.With its diverse genotypes as well as genotypic subtypes,there is a discrepancy in the genotypes used in research compared to their prevalence.HCV genotype 6 which is endemic to South China and Southeast Asia comprises approximately one-third of all HCV infections worldwide,but make up a minority of cases studied in HCV research.Patient concerns:We report a case of HCV-6 seen in an 11-yearold Burmese immigrant to the U.S.and describe the new direct acting antiviral treatment guidelines for pediatrics with HCV genotype 6.Interventions:The patient completed a 12-week course of ledipasvir/sofosbuvir(90 mg/400 mg),per FDA weight-based recommendations for treatment-naive HCV genotypes 4-6,without any complications.Outcomes:The patient was treated successfully with an undetectable HCV viral load one month after treatment completion.Lessons:HCV-6,although previously uncommon in the U.S.,is becoming more prevalent.Updated guidelines include the use of direct acting antivirals,which have been proven effective for HCV-6.Lessons on barriers to care in the immigrant population as well as the value of HCV genotyping are also discussed.展开更多
The CRISPR/Cas9 system has been tailored to a revolutionary genetic tool because of its remarkable simplicity and efficacy.While complex genome editing in the mouse since the 1990 s has been dominated by the use of em...The CRISPR/Cas9 system has been tailored to a revolutionary genetic tool because of its remarkable simplicity and efficacy.While complex genome editing in the mouse since the 1990 s has been dominated by the use of embryonic stem（ES） cells,CRISPR/Cas9 now offers a versatile and fast approach to precisely modify virtually any DNA regions directly in mouse zygotes.Yet,this relative simplicity does not preclude a conscientious preparatory work that is often neglected when initiating a project.Here,we describe the key steps leading to successful generation of a double knockout（KO） mouse by simultaneously targeting two homolog genes,Tmem176 a and Tmem176 b,which are located in the same genomic locus.Additionally,we show that similar efficiency can be obtained in a mixed genetic background or directly in the C57BL/6 inbred strain.Thus,presented as a detailed case study that should be helpful to the non-specialists,we focus on the genotyping strategy to anticipate the various possibilities.展开更多
基金Supported by Research Unit of Hepatitis and Liver Cancer,Chulalongkorn UniversityThe Scholarship Program for Neighboring Countries,Chulalongkorn University+6 种基金The Higher Education Research Promotion and National Research University Project of Thailand,HR1155A-55Thailand Research Fund,DPG5480002,BRG5580005Office of the Commission on Higher EducationCenter of Excellence in Clinical Virology,Chulalongkorn UniversityIntegrated Innovation Academic Center IIAC Chulalongkorn University Centenary Academic Development Project,CU56-HR01)the Ratchadaphiseksomphot Endowment Fund of Chulalongkorn University,RES560530093King Chulalongkorn Memorial Hospital
文摘Hepatitis C virus (HCV) is a serious public health problem affecting 170 million carriers worldwide. It is a leading cause of chronic hepatitis, cirrhosis, and liver cancer and is the primary cause for liver transplantation worldwide. HCV genotype 6 (HCV-6) is restricted to South China, South-East Asia, and it is also occasionally found in migrant patients from endemic countries. HCV-6 has considerable genetic diversity with 23 subtypes (a to w). Although direct sequencing followed by phylogenetic analysis is the gold standard for HCV-6 genotyping and subtyping, there are also now rapid genotyping tests available such as the reverse hybridization line probe assay (INNO-LiPA II; Innogenetics, Zwijnaarde, Belgium). HCV-6 patients present with similar clinical manifestations as patients infected with other genotypes. Based on current evidence, the optimal treatment duration of HCV-6 with pegylated interferon/ribavirin should be 48 wk, although a shortened treatment duration of 24 wk could be sufficient in patients with low pretreatment viral load who achieve rapid virological response. In addition, the development of direct-acting antiviral agents is ongoing, and they give high response rate when combined with standard therapy. Herein, we review the epidemiology, classification, diagnosis and treatment as it pertain to HCV-6.
基金Supported by Chulalongkorn University,No.RES560530155Thailand Research Fund,No.BRG5580005,and No.DPG5480002+2 种基金Joint Research Program between National Research Council of Thailand and Japan Society for the Promotion of Science,Centenary Academic Development Project,No.CU56-HR01Ratchadapiseksompotch Fund(Faculty of Medicine),Integrated Innovation Academic Center and Postdoctoral of Ratchadaphiseksomphot Endowment Fund,Chulalongkorn UniversityHigher Education Research Promotion and National Research University Project of Thailand,Office of the Higher Education Commission,No.HR1155A
文摘AIM: To investigate the early viral kinetics and interleukin-28B (IL28B) polymorphisms of hepatitis C genotype 6 during pegylated interferon and ribavirin therapy.
文摘Rationale:Hepatitis C in the pediatric population is a large health burden globally.With its diverse genotypes as well as genotypic subtypes,there is a discrepancy in the genotypes used in research compared to their prevalence.HCV genotype 6 which is endemic to South China and Southeast Asia comprises approximately one-third of all HCV infections worldwide,but make up a minority of cases studied in HCV research.Patient concerns:We report a case of HCV-6 seen in an 11-yearold Burmese immigrant to the U.S.and describe the new direct acting antiviral treatment guidelines for pediatrics with HCV genotype 6.Interventions:The patient completed a 12-week course of ledipasvir/sofosbuvir(90 mg/400 mg),per FDA weight-based recommendations for treatment-naive HCV genotypes 4-6,without any complications.Outcomes:The patient was treated successfully with an undetectable HCV viral load one month after treatment completion.Lessons:HCV-6,although previously uncommon in the U.S.,is becoming more prevalent.Updated guidelines include the use of direct acting antivirals,which have been proven effective for HCV-6.Lessons on barriers to care in the immigrant population as well as the value of HCV genotyping are also discussed.
基金supported by the Labex IGO project(n°ANR11-LABX-0016-01)funded by the "Investissements d'Avenir" French Government program,managed by the French National Research Agency(ANR)+1 种基金the context of the IHU-Cesti project(EXT173947) which received French government financial support managed by the National Research Agency via the "Investment Into The Future program" ANR-10-IBHU-005supported by Nantes Metropole and Region Pays de la Loire. C.L.was supported by Fondation Progreffe
文摘The CRISPR/Cas9 system has been tailored to a revolutionary genetic tool because of its remarkable simplicity and efficacy.While complex genome editing in the mouse since the 1990 s has been dominated by the use of embryonic stem（ES） cells,CRISPR/Cas9 now offers a versatile and fast approach to precisely modify virtually any DNA regions directly in mouse zygotes.Yet,this relative simplicity does not preclude a conscientious preparatory work that is often neglected when initiating a project.Here,we describe the key steps leading to successful generation of a double knockout（KO） mouse by simultaneously targeting two homolog genes,Tmem176 a and Tmem176 b,which are located in the same genomic locus.Additionally,we show that similar efficiency can be obtained in a mixed genetic background or directly in the C57BL/6 inbred strain.Thus,presented as a detailed case study that should be helpful to the non-specialists,we focus on the genotyping strategy to anticipate the various possibilities.
