BACKGROUND Antiviral treatment of patients with chronic hepatitis B(CHB)in the grey zone of treatment comands risk management in order to optimize the health outcome.In this sense,the identification of HBV mutants rel...BACKGROUND Antiviral treatment of patients with chronic hepatitis B(CHB)in the grey zone of treatment comands risk management in order to optimize the health outcome.In this sense,the identification of HBV mutants related with an increased risk of hepatocellular carcinoma(HCC)could be useful to identify subpopulations with potential indication of antiviral treatment.AIM To analyze the prevalence/persistence of hepatitis B virus(HBV)preS and basal core promoter(BCP)/precore/core variants associated to HCC development in CHB patients in the grey zone.METHODS Work was designed as a longitudinal retrospective study,including 106 plasma samples from 31 patients with CHB in the grey zone of treatment:Hepatitis B e antigen negative,HBV-DNA levels between 12-20000 IU/mL,normal or discordant transaminase levels during follow up and mild/moderate necroinflammatory activity in liver biopsy or Fibroscan(up to 9.5 kPa).Serum HBVDNA was tested using the Abbott Real Time HBV Assay and the BCP/precore/core and the hepatitis B surface antigen(HBsAg)coding regions were analyzed in positive samples by PCR/bulk-sequencing to identify the HCCrelated HBV mutants.RESULTS High-risk HCC related mutants were detected in 24(77%)patients:19(61%)in the BCP/precore/core,and 7(23%)in the HBsAg coding region(2 preS1 and 5 preS2 deletions).The prevalence of preS deletions was genotype-dependent:3/5(60%)patients with preS2 deletions and 1/2 with preS1 deletions were infected with the HBV-E genotype.Since HBV-E was the most prevalent in sub-Saharan patients,a correlation between preS deletions and ethnicity was also found:6/8(75%)sub-Saharan vs 1/19(5%)Caucasian patients had preS deletions(P=0.00016).Remarkably,this correlation was maintained in those patients infected with HBV-A,a minor genotype in sub-Saharan patients:2/2 patients infected with HBV-A from West Africa vs 0/6 of Caucasian origin had preS deletions.The HCC related variants were the major strains and persisted over time(up to 48 mo).Patients with preS deletions had a significant higher prevalence of F2 fibrosis stage than the negatives(57%vs 10%,P=0.0078).CONCLUSION HBV genetic analysis of selected populations,like sub-Saharans infected with HBV-E/A genotypes,will allow identification of subpopulations with risk of HCC development due to accumulation of high-risk HBV variants,thus commanding their increased clinical surveillance.展开更多
慢性乙型肝炎病毒(hepatitis B virus,HBV)感染的防治依然任重而道远.即使我国新版指南扩大了抗病毒治疗适应证,依然有一定比例的HBV感染者不符合抗病毒治疗适应证,称之为不确定期或灰区(grey zone,GZ).但当前关于不确定期或GZ的解读与...慢性乙型肝炎病毒(hepatitis B virus,HBV)感染的防治依然任重而道远.即使我国新版指南扩大了抗病毒治疗适应证,依然有一定比例的HBV感染者不符合抗病毒治疗适应证,称之为不确定期或灰区(grey zone,GZ).但当前关于不确定期或GZ的解读与判断标准较为混乱,两者之间的联系与区别还不甚清晰,不同研究所指向的对象不尽相同.但无论如何认定不确定期或GZ,其目的是为了及时、准确判断慢性HBV感染的疾病进展与是否需要及时治疗.基于GZ对应于“治疗的适应证分类”和不确定期对应于“自然史分期”的理解,本文结合国内外的研究进展阐述对慢性HBV感染不确定期与GZ的再认识.GZ即为不治疗对象(不符合抗病毒治疗适应证),而不确定期仅为难以明确归于自然史分期(不符合自然史分期)的患者,GZ应包括不确定期,而不是等同关系.对应我国新版指南标准,属于GZ的不确定期患者,建议抗病毒治疗;对应欧洲肝病学会2017年指南标准,免疫控制期与属于GZ的不确定期患者,建议抗病毒治疗.展开更多
The BG110E high-strength expansion pipe was developed using medium manganese steel and subjected to a two-phase zone heat treatment process.Mechanical properties and microstructure analysis results have proven that th...The BG110E high-strength expansion pipe was developed using medium manganese steel and subjected to a two-phase zone heat treatment process.Mechanical properties and microstructure analysis results have proven that the BG110E expansion pipe exhibits uniform elongation of more than 19%.Moreover,after undergoing expan-sion deformation,its strength,toughness,and plasticity are found to meet the stringent requirements of the P110 pipe.The microstructure of this high-strength expansion pipe,which has a strength of 110 ksi(1 ksi=6.895 MPa),consists of tempered martensite,ferrite,retained austenite,and granular bainite.The propotion of retained austenite reaches up to 12%,ensuring high plasticity and the occurrence of the transformation-induced plasticity effect during the deformation process.Consequently,it enhances the coordinated deformation ability between different phases,which significantly improves the internal yield pressure of the BG110E high-strength expansion pipe in turn.展开更多
基金Supported by Análisis genético y epigenético del VHB en pacientes portadores asintomáticos.Implicaciones en la decisión terapéutica funded in the 1~(st) Edition of the Gilead Fellowship Program,No.GLD13/00046 and Modificaciones de los niveles de expresión génica mediada por mutantes naturales de la región PreS del virus de la hepatitis B,y asociación con genes implicados en el desarrollo de hepatocarcinoma Efecto del tratamiento antiviral
文摘BACKGROUND Antiviral treatment of patients with chronic hepatitis B(CHB)in the grey zone of treatment comands risk management in order to optimize the health outcome.In this sense,the identification of HBV mutants related with an increased risk of hepatocellular carcinoma(HCC)could be useful to identify subpopulations with potential indication of antiviral treatment.AIM To analyze the prevalence/persistence of hepatitis B virus(HBV)preS and basal core promoter(BCP)/precore/core variants associated to HCC development in CHB patients in the grey zone.METHODS Work was designed as a longitudinal retrospective study,including 106 plasma samples from 31 patients with CHB in the grey zone of treatment:Hepatitis B e antigen negative,HBV-DNA levels between 12-20000 IU/mL,normal or discordant transaminase levels during follow up and mild/moderate necroinflammatory activity in liver biopsy or Fibroscan(up to 9.5 kPa).Serum HBVDNA was tested using the Abbott Real Time HBV Assay and the BCP/precore/core and the hepatitis B surface antigen(HBsAg)coding regions were analyzed in positive samples by PCR/bulk-sequencing to identify the HCCrelated HBV mutants.RESULTS High-risk HCC related mutants were detected in 24(77%)patients:19(61%)in the BCP/precore/core,and 7(23%)in the HBsAg coding region(2 preS1 and 5 preS2 deletions).The prevalence of preS deletions was genotype-dependent:3/5(60%)patients with preS2 deletions and 1/2 with preS1 deletions were infected with the HBV-E genotype.Since HBV-E was the most prevalent in sub-Saharan patients,a correlation between preS deletions and ethnicity was also found:6/8(75%)sub-Saharan vs 1/19(5%)Caucasian patients had preS deletions(P=0.00016).Remarkably,this correlation was maintained in those patients infected with HBV-A,a minor genotype in sub-Saharan patients:2/2 patients infected with HBV-A from West Africa vs 0/6 of Caucasian origin had preS deletions.The HCC related variants were the major strains and persisted over time(up to 48 mo).Patients with preS deletions had a significant higher prevalence of F2 fibrosis stage than the negatives(57%vs 10%,P=0.0078).CONCLUSION HBV genetic analysis of selected populations,like sub-Saharans infected with HBV-E/A genotypes,will allow identification of subpopulations with risk of HCC development due to accumulation of high-risk HBV variants,thus commanding their increased clinical surveillance.
文摘慢性乙型肝炎病毒(hepatitis B virus,HBV)感染的防治依然任重而道远.即使我国新版指南扩大了抗病毒治疗适应证,依然有一定比例的HBV感染者不符合抗病毒治疗适应证,称之为不确定期或灰区(grey zone,GZ).但当前关于不确定期或GZ的解读与判断标准较为混乱,两者之间的联系与区别还不甚清晰,不同研究所指向的对象不尽相同.但无论如何认定不确定期或GZ,其目的是为了及时、准确判断慢性HBV感染的疾病进展与是否需要及时治疗.基于GZ对应于“治疗的适应证分类”和不确定期对应于“自然史分期”的理解,本文结合国内外的研究进展阐述对慢性HBV感染不确定期与GZ的再认识.GZ即为不治疗对象(不符合抗病毒治疗适应证),而不确定期仅为难以明确归于自然史分期(不符合自然史分期)的患者,GZ应包括不确定期,而不是等同关系.对应我国新版指南标准,属于GZ的不确定期患者,建议抗病毒治疗;对应欧洲肝病学会2017年指南标准,免疫控制期与属于GZ的不确定期患者,建议抗病毒治疗.
文摘The BG110E high-strength expansion pipe was developed using medium manganese steel and subjected to a two-phase zone heat treatment process.Mechanical properties and microstructure analysis results have proven that the BG110E expansion pipe exhibits uniform elongation of more than 19%.Moreover,after undergoing expan-sion deformation,its strength,toughness,and plasticity are found to meet the stringent requirements of the P110 pipe.The microstructure of this high-strength expansion pipe,which has a strength of 110 ksi(1 ksi=6.895 MPa),consists of tempered martensite,ferrite,retained austenite,and granular bainite.The propotion of retained austenite reaches up to 12%,ensuring high plasticity and the occurrence of the transformation-induced plasticity effect during the deformation process.Consequently,it enhances the coordinated deformation ability between different phases,which significantly improves the internal yield pressure of the BG110E high-strength expansion pipe in turn.