BACKGROUND Genetic disorders affecting hepatobiliary transporters can be triggered by various factors,resulting in marked cholestasis.CASE SUMMARY We report two patients who experienced a severe episode of intrahepati...BACKGROUND Genetic disorders affecting hepatobiliary transporters can be triggered by various factors,resulting in marked cholestasis.CASE SUMMARY We report two patients who experienced a severe episode of intrahepatic cholestasis triggered by an acute hepatitis E virus infection.Following an extensive clinical examination that ruled out common causes of cholestatic liver damage,we conducted next-generation sequencing to determine the genetic profiles of the patients.The analysis revealed several known and unknown variants in genes associated with hepatobiliary transporters and bile salt regulation,including ATP8B1,ABCB11,ABCB4,MYO5B,and FXR.For a comprehensive understanding of the pathophysiology,we performed ClinVar analysis and utilized PolyPhen for bioinformatic prediction of functional impact.Both patients exhibited rapid symptom improvement and a decrease in hyperbilirubinemia when treated with either rifampicin or bezafibrate.CONCLUSION Our findings introduce hepatitis E viral infection as a novel trigger for intrahepatic cholestasis,and we categorize the significance of the various genetic variants based on the current state of research.展开更多
The aim of this study was to investigate an association between the development of cholangiocarcinoma(CCA)and the ABO variant rs505922(known to increase pan-creatic cancer risk)in a large cohort of European individual...The aim of this study was to investigate an association between the development of cholangiocarcinoma(CCA)and the ABO variant rs505922(known to increase pan-creatic cancer risk)in a large cohort of European individuals with CCA.In total,180 individuals with CCA and 350 CCA-free controls were included.The ABO variant rs505922 was genotyped using a polymerase chain reaction-based assay.Association between this single nucleotide polymorphism(SNP)and CCA was tested in contingency tables.Neither allele distributions nor association tests and regression analysis provided evidence for an increased risk of CCA among carriers of the ABO variant(all P > 0.05).Nevertheless,we documented a deviation from Hardy-Weinberg equilibrium in the entire CCA cohort(P = 0.028)and for patients with intrahe-patic(P = 0.037)but not extrahepatic tumor localization(P > 0.05).The association tests did not provide evidence for a prominent role of the investigated SNP in the genetic risk of CCA.However,Hardy-Weinberg disequilibrium in the entire cohort and the intrahepatic CCA subgroup warrants future studies investigating a potential CCA risk modulation by individual blood groups.展开更多
BACKGROUND Bacterial infections(BI)negatively affect the natural course of cirrhosis.The most frequent BI are urinary tract infections(UTI),pneumonia,and spontaneousbacterial peritonitis(SBP).AIM To assess the relevan...BACKGROUND Bacterial infections(BI)negatively affect the natural course of cirrhosis.The most frequent BI are urinary tract infections(UTI),pneumonia,and spontaneousbacterial peritonitis(SBP).AIM To assess the relevance of bacterial infections beyond the commonly recognized types in patients with cirrhosis and to investigate their relationship with other clinical variables.METHODS We retrospectively analyzed patients with cirrhosis and BI treated between 2015 and 2018 at our tertiary care center.BIs were classified as typical and atypical,and clinical as well as laboratory parameters were compared between the two groups.RESULTS In a cohort of 488 patients with cirrhosis,we identified 225 typical BI(95 UTI,73 SBP,72 pulmonary infections)and 74 atypical BIs,predominantly cholangitis and soft tissue infections(21 each),followed by intra-abdominal BIs(n=9),cholecystitis(n=6),head/throat BIs(n=6),osteoarticular BIs(n=5),and endocarditis(n=3).We did not observe differences concerning age,sex,or etiology of cirrhosis in patients with typical vs atypical BI.Atypical BIs were more common in patients with more advanced cirrhosis,as evidenced by Model of End Stage Liver Disease(15.1±7.4 vs 12.9±5.1;P=0.005)and Child-Pugh scores(8.6±2.5 vs 8.0±2;P=0.05).CONCLUSION Atypical BIs in cirrhosis patients exhibit a distinct spectrum and are associated with more advanced stages of the disease.Hence,the work-up of cirrhosis patients with suspected BI requires detailed work-up to elucidate whether typical BI can be identified.展开更多
Background The frequency of childhood obesity has increased over the last 3 decades,and the trend constitutes a worrisome epidemic worldwide.With the raising obesity risk,key aspects to consider are accurate body mass...Background The frequency of childhood obesity has increased over the last 3 decades,and the trend constitutes a worrisome epidemic worldwide.With the raising obesity risk,key aspects to consider are accurate body mass index classification,as well as metabolic and cardiovascular,and hepatic consequences.Data sources The authors performed a systematic literature search in PubMed and EMBASE,using selected key words(obesity,childhood,cardiovascular,liver health).In particular,they focused their search on papers evaluating the impact of obesity on cardiovascular and liver health.Results We evaluated the current literature dealing with the impact of excessive body fat accumulation in childhood and across adulthood,as a predisposing factor to cardiovascular and hepatic alterations.We also evaluated the impact of physical and dietary behaviors starting from childhood on cardio-metabolic consequences.Conclusions The epidemic of obesity and obesity-related comorbidities worldwide raises concerns about the impact of early abnormalities during childhood and adolescence.Two key abnormalities in this context include cardiovascular diseases,and non-alcoholic fatty liver disease.Appropriate metabolic screenings and associated comorbidities should start as early as possible in obese children and adolescents.Nevertheless,improving dietary intake and increasing physical activity performance are to date the best therapeutic tools in children to weaken the onset of obesity,cardiovascular diseases,and diabetes risk during adulthood.展开更多
High-quality DNA extraction is a crucial step in metagenomic studies.Bias by different isolation kits impairs the comparison across datasets.A trending topic is,however,the analysis of multiple metagenomes from the sa...High-quality DNA extraction is a crucial step in metagenomic studies.Bias by different isolation kits impairs the comparison across datasets.A trending topic is,however,the analysis of multiple metagenomes from the same patients to draw a holistic picture of microbiota associated with diseases.We thus collected bile,stool,saliva,plaque,sputum,and conjunctival swab samples and performed DNA extraction with three commercial kits.For each combination of the specimen type and DNA extraction kit,20-gigabase(Gb)metagenomic data were generated using short-read sequencing.While profiles of the specimen types showed close proximity to each other,we observed notable differences in the alpha diversity and composition of the microbiota depending on the DNA extraction kits.No kit outperformed all selected kits on every specimen.We reached consistently good results using the Qiagen QiAamp DNA Microbiome Kit.Depending on the specimen,our data indicate that over 10 Gb of sequencing data are required to achieve sufficient resolution,but DNA-based identification is superior to identification by mass spectrometry.Finally,longread nanopore sequencing confirmed the results(correlation coefficient>0.98).Our results thus suggest using a strategy with only one kit for studies aiming for a direct comparison of multiple microbiotas from the same patients.展开更多
文摘BACKGROUND Genetic disorders affecting hepatobiliary transporters can be triggered by various factors,resulting in marked cholestasis.CASE SUMMARY We report two patients who experienced a severe episode of intrahepatic cholestasis triggered by an acute hepatitis E virus infection.Following an extensive clinical examination that ruled out common causes of cholestatic liver damage,we conducted next-generation sequencing to determine the genetic profiles of the patients.The analysis revealed several known and unknown variants in genes associated with hepatobiliary transporters and bile salt regulation,including ATP8B1,ABCB11,ABCB4,MYO5B,and FXR.For a comprehensive understanding of the pathophysiology,we performed ClinVar analysis and utilized PolyPhen for bioinformatic prediction of functional impact.Both patients exhibited rapid symptom improvement and a decrease in hyperbilirubinemia when treated with either rifampicin or bezafibrate.CONCLUSION Our findings introduce hepatitis E viral infection as a novel trigger for intrahepatic cholestasis,and we categorize the significance of the various genetic variants based on the current state of research.
文摘The aim of this study was to investigate an association between the development of cholangiocarcinoma(CCA)and the ABO variant rs505922(known to increase pan-creatic cancer risk)in a large cohort of European individuals with CCA.In total,180 individuals with CCA and 350 CCA-free controls were included.The ABO variant rs505922 was genotyped using a polymerase chain reaction-based assay.Association between this single nucleotide polymorphism(SNP)and CCA was tested in contingency tables.Neither allele distributions nor association tests and regression analysis provided evidence for an increased risk of CCA among carriers of the ABO variant(all P > 0.05).Nevertheless,we documented a deviation from Hardy-Weinberg equilibrium in the entire CCA cohort(P = 0.028)and for patients with intrahe-patic(P = 0.037)but not extrahepatic tumor localization(P > 0.05).The association tests did not provide evidence for a prominent role of the investigated SNP in the genetic risk of CCA.However,Hardy-Weinberg disequilibrium in the entire cohort and the intrahepatic CCA subgroup warrants future studies investigating a potential CCA risk modulation by individual blood groups.
文摘BACKGROUND Bacterial infections(BI)negatively affect the natural course of cirrhosis.The most frequent BI are urinary tract infections(UTI),pneumonia,and spontaneousbacterial peritonitis(SBP).AIM To assess the relevance of bacterial infections beyond the commonly recognized types in patients with cirrhosis and to investigate their relationship with other clinical variables.METHODS We retrospectively analyzed patients with cirrhosis and BI treated between 2015 and 2018 at our tertiary care center.BIs were classified as typical and atypical,and clinical as well as laboratory parameters were compared between the two groups.RESULTS In a cohort of 488 patients with cirrhosis,we identified 225 typical BI(95 UTI,73 SBP,72 pulmonary infections)and 74 atypical BIs,predominantly cholangitis and soft tissue infections(21 each),followed by intra-abdominal BIs(n=9),cholecystitis(n=6),head/throat BIs(n=6),osteoarticular BIs(n=5),and endocarditis(n=3).We did not observe differences concerning age,sex,or etiology of cirrhosis in patients with typical vs atypical BI.Atypical BIs were more common in patients with more advanced cirrhosis,as evidenced by Model of End Stage Liver Disease(15.1±7.4 vs 12.9±5.1;P=0.005)and Child-Pugh scores(8.6±2.5 vs 8.0±2;P=0.05).CONCLUSION Atypical BIs in cirrhosis patients exhibit a distinct spectrum and are associated with more advanced stages of the disease.Hence,the work-up of cirrhosis patients with suspected BI requires detailed work-up to elucidate whether typical BI can be identified.
基金The present par develops in the context of the project FOIE GRAS,which has received funding from the European Union’s Horizon 2020 Research and Innovation Program under the Marie Sklodowska-Curie Grant Agreement(No.722619).EMM and HS are recipients of Foie Gras Early Research Training Grant.
文摘Background The frequency of childhood obesity has increased over the last 3 decades,and the trend constitutes a worrisome epidemic worldwide.With the raising obesity risk,key aspects to consider are accurate body mass index classification,as well as metabolic and cardiovascular,and hepatic consequences.Data sources The authors performed a systematic literature search in PubMed and EMBASE,using selected key words(obesity,childhood,cardiovascular,liver health).In particular,they focused their search on papers evaluating the impact of obesity on cardiovascular and liver health.Results We evaluated the current literature dealing with the impact of excessive body fat accumulation in childhood and across adulthood,as a predisposing factor to cardiovascular and hepatic alterations.We also evaluated the impact of physical and dietary behaviors starting from childhood on cardio-metabolic consequences.Conclusions The epidemic of obesity and obesity-related comorbidities worldwide raises concerns about the impact of early abnormalities during childhood and adolescence.Two key abnormalities in this context include cardiovascular diseases,and non-alcoholic fatty liver disease.Appropriate metabolic screenings and associated comorbidities should start as early as possible in obese children and adolescents.Nevertheless,improving dietary intake and increasing physical activity performance are to date the best therapeutic tools in children to weaken the onset of obesity,cardiovascular diseases,and diabetes risk during adulthood.
文摘High-quality DNA extraction is a crucial step in metagenomic studies.Bias by different isolation kits impairs the comparison across datasets.A trending topic is,however,the analysis of multiple metagenomes from the same patients to draw a holistic picture of microbiota associated with diseases.We thus collected bile,stool,saliva,plaque,sputum,and conjunctival swab samples and performed DNA extraction with three commercial kits.For each combination of the specimen type and DNA extraction kit,20-gigabase(Gb)metagenomic data were generated using short-read sequencing.While profiles of the specimen types showed close proximity to each other,we observed notable differences in the alpha diversity and composition of the microbiota depending on the DNA extraction kits.No kit outperformed all selected kits on every specimen.We reached consistently good results using the Qiagen QiAamp DNA Microbiome Kit.Depending on the specimen,our data indicate that over 10 Gb of sequencing data are required to achieve sufficient resolution,but DNA-based identification is superior to identification by mass spectrometry.Finally,longread nanopore sequencing confirmed the results(correlation coefficient>0.98).Our results thus suggest using a strategy with only one kit for studies aiming for a direct comparison of multiple microbiotas from the same patients.
