Hepatitis B virus(HBV)is the leading cause of chronic viral hepatitis.Annually,almost two million children younger than 5 years acquire the infection,mostly through vertical or horizontal transmission in early life.Ve...Hepatitis B virus(HBV)is the leading cause of chronic viral hepatitis.Annually,almost two million children younger than 5 years acquire the infection,mostly through vertical or horizontal transmission in early life.Vertical transmission of HBV is a high efficacy phenomenon ranging,in the absence of any preventive interventions,from 70%to 90%for hepatitis e antigen positive mothers and from 10%to 40%for hepatitis e antigen-negative mothers.Maternal viraemia is a preeminent risk factor for vertical transmission of HBV.Maternal screening is the first step to prevent vertical transmission of HBV.Hepatitis B passive and active immunoprophylaxis at birth together with antiviral treatment of highly viraemic mothers are the key strategies for global elimination of HBV infection.Strategies are needed to promote implementation of birth-dose vaccination and hepatitis B immunoglobulins in low-and middle-income countries where the prevalence of the infection is at the highest.展开更多
Hepatitis B virus(HBV)infection is one of the main causes of morbidity and mortality worldwide.Most children acquire the infection perinatally or during early childhood and develop a chronic hepatitis characterized by...Hepatitis B virus(HBV)infection is one of the main causes of morbidity and mortality worldwide.Most children acquire the infection perinatally or during early childhood and develop a chronic hepatitis characterized by a high viral replication and a low-inflammation phase of infection,with normal or only slightly raised aminotransferases.Although a conservative approach in children is usually recommended,different therapies exist and different therapeutic approaches are possible.The main goals of antiviral treatment for children with chronic HBV infection are to suppress viral replication and to warn the disease progression to cirrhosis and hepatocellular carcinoma,although these complications are rare in children.Both United States Food and Drug Administration(USFDA)and European Medicines Agency(EMA)have approved interferon alfa-2b for children aged 1 year and older,pegylated interferon alfa-2a and lamivudine for children aged 3 years and older,entecavir for use in children aged 2 years and older,and adefovir for use in those 12 years of age and older.Tenofovir disoproxil fumarate is approved by EMA for children aged 2 years and older and by USFDA for treatment in children aged 12 years and older.Finally,EMA has approved the use of tenofovir alafenamide for treatment of children aged 12 years and older or for children weighing more than 35 kg independent of age.This narrative review will provide the framework for summarizing indications to antiviral therapy in the management of chronic HBV infection in children and adolescents.展开更多
1 Introduction Kounis syndrome constitutes a coronary hypersensitivity disorder defined by the association of an anaphylactoid,anaphylactic,allergic or hypersensitivity reaction with an acute coronary syndrome,in a ph...1 Introduction Kounis syndrome constitutes a coronary hypersensitivity disorder defined by the association of an anaphylactoid,anaphylactic,allergic or hypersensitivity reaction with an acute coronary syndrome,in a physiopathological context involving various interrelated and interacting inflammatory cells,such as mast-cells,eosinophils and platelets.[1,2]Similar entities to Kounis syndrome might involve cerebral and mesenteric arteries.展开更多
Pegylated interferon (IFN) α-2a or 2b in combination with ribavirin for children aged 3 years and older is the standard treatment for paediatric chronic hepatitis C. This treatment regimen was developed fi...Pegylated interferon (IFN) α-2a or 2b in combination with ribavirin for children aged 3 years and older is the standard treatment for paediatric chronic hepatitis C. This treatment regimen was developed firstly in adults. In recent years, a number of direct-acting antiviral agents (DAAs) are under development for treatment of chronic hepatitis C virus (HCV) infection. These agents block viral replication inhibiting directly one of the several steps of HCV lifecycle. DAAs are classified into several categories based on their molecular target: HCV NS3/4A protease inhibitors, HCV NS5B polymerase inhibitors and HCV NS5A inhibitors. Other promising compounds are cyclophilin A inhibitors, mi-RNA122 and IFN-λ. Several new drugs associations will be developed in the near future starting from the actual standard of care. IFN-based and IFN-free regimens are being studied in adults. In this constantly evolving scenario new drug regimens targeted and suitable for children would be possible in the next future. Especially for children, it is crucial to identify the right combination of drugs with the highest potency, barrier to resistance and the best safety profile.展开更多
AIM:To investigate the diagnostic and therapeutic assessment in children with adenomyomatosis of the gallbladder(AMG).METHODS:AMG is a degenerative disease characterized by a proliferation of the mucosal epithelium wh...AIM:To investigate the diagnostic and therapeutic assessment in children with adenomyomatosis of the gallbladder(AMG).METHODS:AMG is a degenerative disease characterized by a proliferation of the mucosal epithelium which deeply invaginates and extends into the thickened muscular layer of the gallbladder,causing intramural diverticula.Although AMG is found in up to 5%of cholecystectomy specimens in adult populations,this condition in childhood is extremely uncommon.Authors provide a detailed systematic review of the pediatric literature according to PRISMA guidelines,focusing on diagnostic and therapeutic assessment.An additional case of AMG is also presented.RESULTS:Five studies were finally enclosed,encompassing 5 children with AMG.Analysis was extended to our additional 11-year-old patient,who presented diffuse AMG and pancreatic acinar metaplasia of the gallbladder mucosa and was successfully managed with laparoscopic cholecystectomy.Mean age at presentation was 7.2 years.Unspecific abdominal pain was the commonest symptom.Abdominal ultrasound was performed on all patients,with a diagnostic accuracy of 100%.Five patients underwent cholecystectomy,and at follow-up were asymptomatic.In the remaining patient,completely asymptomatic at diagnosis,a conservative approach with monthly monitoring via ultrasonography was undertaken.CONCLUSION:Considering the remote but possible degeneration leading to cancer and the feasibility of laparoscopic cholecystectomy even in small children,evidence suggests that elective laparoscopic cholecystectomy represent the treatment of choice.Preoperative evaluation of the extrahepatic biliary tree anatomy with cholangio-MRI is strongly recommended.展开更多
The purpose of the present review is to summarise the current knowledge on the association between single nucleotide polymorphisms (SNPs) in the interferon L3 (IFNL3) gene and hepatitis C virus (HCV) infection in chil...The purpose of the present review is to summarise the current knowledge on the association between single nucleotide polymorphisms (SNPs) in the interferon L3 (IFNL3) gene and hepatitis C virus (HCV) infection in children. Many studies in adults have demonstrated that genetic variation in IFNL3 is a strong predictor of the virological response in treatment-naive patients with HCV genotype 1 who were treated with Pegylated-IFN-α and ribavirin. Genetic variation in IFNL3 is also associated with the spontaneous clearance of HCV. Thus far, few paediatric studies have explored the association between variations in the IFNL3 gene and either spontaneous or treatment-induced clearance of HCV. The CC genotype of the rs12979860 SNP is associated with the spontaneous clearance of HCV in children independently of HCV genotype. Four paediatric studies have shown that both the CC genotype of the rs12979860 SNP and the TT genotype of the rs8099917 SNP are associated with the treatment-induced (IFN monotherapy and Pegylated-IFN-α and ribavirin association) clearance of HCV, while the rs12980275 SNP did not affect the virological response. The possible role of IFNL3 gene variation as a pre-treatment and on-treatment predictor of virological response in children is highly attractive but still undetermined. Further paediatric studies are needed to evaluate if testing for SNPs in IFNL3, either alone or together with other predictors of response to treatment, could be used to direct treatment strategies, including an avoidance of unnecessary protease inhibitor therapy and the duration of treatment.展开更多
Chronic infections by hepatitis B virus(HBV)and hepatitis C virus(HCV)major causes of advanced liver disease and mortality worldwide.Although regarded as benign infections in children,their persistence through adultho...Chronic infections by hepatitis B virus(HBV)and hepatitis C virus(HCV)major causes of advanced liver disease and mortality worldwide.Although regarded as benign infections in children,their persistence through adulthood is undoubtedly of concern.Recent advances in HCV treatment have restored the visibility of these conditions and raised expectations for HBV treatment,which is currently far from being curative.Herein we describe direct-acting antivirals available for pediatric HCV(sofosbuvir/ledipasvir,sofosbuvir/velpatasvir,glecaprevir/pibrentasvir)and their real-world use.A critical review of the HBV pediatric classification is provided.Anti-HBV investigational compounds are reviewed in light of the pathophysiology in the pediatric population,including capsid assembly modulators,antigen secretion inhibitors,silencing RNAs,and immune modifiers.Recommendations for screening and management of immunosuppressed children or those with other risk factors or comorbidities are also summarized.展开更多
文摘Hepatitis B virus(HBV)is the leading cause of chronic viral hepatitis.Annually,almost two million children younger than 5 years acquire the infection,mostly through vertical or horizontal transmission in early life.Vertical transmission of HBV is a high efficacy phenomenon ranging,in the absence of any preventive interventions,from 70%to 90%for hepatitis e antigen positive mothers and from 10%to 40%for hepatitis e antigen-negative mothers.Maternal viraemia is a preeminent risk factor for vertical transmission of HBV.Maternal screening is the first step to prevent vertical transmission of HBV.Hepatitis B passive and active immunoprophylaxis at birth together with antiviral treatment of highly viraemic mothers are the key strategies for global elimination of HBV infection.Strategies are needed to promote implementation of birth-dose vaccination and hepatitis B immunoglobulins in low-and middle-income countries where the prevalence of the infection is at the highest.
文摘Hepatitis B virus(HBV)infection is one of the main causes of morbidity and mortality worldwide.Most children acquire the infection perinatally or during early childhood and develop a chronic hepatitis characterized by a high viral replication and a low-inflammation phase of infection,with normal or only slightly raised aminotransferases.Although a conservative approach in children is usually recommended,different therapies exist and different therapeutic approaches are possible.The main goals of antiviral treatment for children with chronic HBV infection are to suppress viral replication and to warn the disease progression to cirrhosis and hepatocellular carcinoma,although these complications are rare in children.Both United States Food and Drug Administration(USFDA)and European Medicines Agency(EMA)have approved interferon alfa-2b for children aged 1 year and older,pegylated interferon alfa-2a and lamivudine for children aged 3 years and older,entecavir for use in children aged 2 years and older,and adefovir for use in those 12 years of age and older.Tenofovir disoproxil fumarate is approved by EMA for children aged 2 years and older and by USFDA for treatment in children aged 12 years and older.Finally,EMA has approved the use of tenofovir alafenamide for treatment of children aged 12 years and older or for children weighing more than 35 kg independent of age.This narrative review will provide the framework for summarizing indications to antiviral therapy in the management of chronic HBV infection in children and adolescents.
文摘1 Introduction Kounis syndrome constitutes a coronary hypersensitivity disorder defined by the association of an anaphylactoid,anaphylactic,allergic or hypersensitivity reaction with an acute coronary syndrome,in a physiopathological context involving various interrelated and interacting inflammatory cells,such as mast-cells,eosinophils and platelets.[1,2]Similar entities to Kounis syndrome might involve cerebral and mesenteric arteries.
文摘Pegylated interferon (IFN) α-2a or 2b in combination with ribavirin for children aged 3 years and older is the standard treatment for paediatric chronic hepatitis C. This treatment regimen was developed firstly in adults. In recent years, a number of direct-acting antiviral agents (DAAs) are under development for treatment of chronic hepatitis C virus (HCV) infection. These agents block viral replication inhibiting directly one of the several steps of HCV lifecycle. DAAs are classified into several categories based on their molecular target: HCV NS3/4A protease inhibitors, HCV NS5B polymerase inhibitors and HCV NS5A inhibitors. Other promising compounds are cyclophilin A inhibitors, mi-RNA122 and IFN-λ. Several new drugs associations will be developed in the near future starting from the actual standard of care. IFN-based and IFN-free regimens are being studied in adults. In this constantly evolving scenario new drug regimens targeted and suitable for children would be possible in the next future. Especially for children, it is crucial to identify the right combination of drugs with the highest potency, barrier to resistance and the best safety profile.
文摘AIM:To investigate the diagnostic and therapeutic assessment in children with adenomyomatosis of the gallbladder(AMG).METHODS:AMG is a degenerative disease characterized by a proliferation of the mucosal epithelium which deeply invaginates and extends into the thickened muscular layer of the gallbladder,causing intramural diverticula.Although AMG is found in up to 5%of cholecystectomy specimens in adult populations,this condition in childhood is extremely uncommon.Authors provide a detailed systematic review of the pediatric literature according to PRISMA guidelines,focusing on diagnostic and therapeutic assessment.An additional case of AMG is also presented.RESULTS:Five studies were finally enclosed,encompassing 5 children with AMG.Analysis was extended to our additional 11-year-old patient,who presented diffuse AMG and pancreatic acinar metaplasia of the gallbladder mucosa and was successfully managed with laparoscopic cholecystectomy.Mean age at presentation was 7.2 years.Unspecific abdominal pain was the commonest symptom.Abdominal ultrasound was performed on all patients,with a diagnostic accuracy of 100%.Five patients underwent cholecystectomy,and at follow-up were asymptomatic.In the remaining patient,completely asymptomatic at diagnosis,a conservative approach with monthly monitoring via ultrasonography was undertaken.CONCLUSION:Considering the remote but possible degeneration leading to cancer and the feasibility of laparoscopic cholecystectomy even in small children,evidence suggests that elective laparoscopic cholecystectomy represent the treatment of choice.Preoperative evaluation of the extrahepatic biliary tree anatomy with cholangio-MRI is strongly recommended.
文摘The purpose of the present review is to summarise the current knowledge on the association between single nucleotide polymorphisms (SNPs) in the interferon L3 (IFNL3) gene and hepatitis C virus (HCV) infection in children. Many studies in adults have demonstrated that genetic variation in IFNL3 is a strong predictor of the virological response in treatment-naive patients with HCV genotype 1 who were treated with Pegylated-IFN-α and ribavirin. Genetic variation in IFNL3 is also associated with the spontaneous clearance of HCV. Thus far, few paediatric studies have explored the association between variations in the IFNL3 gene and either spontaneous or treatment-induced clearance of HCV. The CC genotype of the rs12979860 SNP is associated with the spontaneous clearance of HCV in children independently of HCV genotype. Four paediatric studies have shown that both the CC genotype of the rs12979860 SNP and the TT genotype of the rs8099917 SNP are associated with the treatment-induced (IFN monotherapy and Pegylated-IFN-α and ribavirin association) clearance of HCV, while the rs12980275 SNP did not affect the virological response. The possible role of IFNL3 gene variation as a pre-treatment and on-treatment predictor of virological response in children is highly attractive but still undetermined. Further paediatric studies are needed to evaluate if testing for SNPs in IFNL3, either alone or together with other predictors of response to treatment, could be used to direct treatment strategies, including an avoidance of unnecessary protease inhibitor therapy and the duration of treatment.
文摘Chronic infections by hepatitis B virus(HBV)and hepatitis C virus(HCV)major causes of advanced liver disease and mortality worldwide.Although regarded as benign infections in children,their persistence through adulthood is undoubtedly of concern.Recent advances in HCV treatment have restored the visibility of these conditions and raised expectations for HBV treatment,which is currently far from being curative.Herein we describe direct-acting antivirals available for pediatric HCV(sofosbuvir/ledipasvir,sofosbuvir/velpatasvir,glecaprevir/pibrentasvir)and their real-world use.A critical review of the HBV pediatric classification is provided.Anti-HBV investigational compounds are reviewed in light of the pathophysiology in the pediatric population,including capsid assembly modulators,antigen secretion inhibitors,silencing RNAs,and immune modifiers.Recommendations for screening and management of immunosuppressed children or those with other risk factors or comorbidities are also summarized.
