Background:Cirrhosis with acute decompensation(AD)and acute-on-chronic liver failure(ACLF)are characterized by high morbidity and mortality.Cytolysin,a toxin from Enterococcus faecalis(E.faecalis),is associated with m...Background:Cirrhosis with acute decompensation(AD)and acute-on-chronic liver failure(ACLF)are characterized by high morbidity and mortality.Cytolysin,a toxin from Enterococcus faecalis(E.faecalis),is associated with mortality in alcohol-associated hepatitis(AH).It is unclear whether cytolysin also contributes to disease severity in AD and ACLF.Methods:We studied the role of fecal cytolysin in 78 cirrhotic patients with AD/ACLF.Bacterial DNA from fecal samples was extracted and real-time quantitative polymerase chain reaction(PCR)was performed.The association between fecal cytolysin and liver disease severity in cirrhosis with AD or ACLF was analyzed.Results:Fecal cytolysin and E.faecalis abundance did not predict chronic liver failure(CLIF-C)AD and ACLF scores.Presence of fecal cytolysin was not associated with other liver disease markers,including Fibrosis-4(FIB-4)index,‘Age,serum Bilirubin,INR,and serum Creatinine(ABIC)’score,Child-Pugh score,model for end-stage liver disease(MELD)nor MELD-Na scores in AD or ACLF patients.Conclusions:Fecal cytolysin does not predict disease severity in AD and ACLF patients.The predictive value of fecal cytolysin positivity for mortality appears to be restricted to AH.展开更多
Nonalcoholic fatty liver disease(NAFLD)is the leading cause of chronic liver disease worldwide among children and adolescents.It encompasses a spectrum of disease,from its mildest form of isolated steatosis,to nonalco...Nonalcoholic fatty liver disease(NAFLD)is the leading cause of chronic liver disease worldwide among children and adolescents.It encompasses a spectrum of disease,from its mildest form of isolated steatosis,to nonalcoholic steatohepatitis(NASH)to liver fibrosis and cirrhosis,or end-stage liver disease.The early diagnosis of pediatric NAFLD is crucial in preventing disease progression and in improving outcomes.Currently,liver biopsy is the gold standard for diagnosing NAFLD.However,given its invasive nature,there has been significant interest in developing noninvasive methods that can be used as accurate alternatives.Here,we review noninvasive biomarkers in pediatric NAFLD,focusing primarily on the diagnostic accuracy of various biomarkers as measured by their area under the receiver operating characteristic,sensitivity,and specificity.We examine two major approaches to noninvasive biomarkers in children with NAFLD.First,the biological approach that quantifies serological biomarkers.This includes the study of individual circulating molecules as biomarkers as well as the use of composite algorithms derived from combinations of biomarkers.The second is a more physical approach that examines data measured through imaging techniques as noninvasive biomarkers for pediatric NAFLD.Each of these approaches was applied to children with NAFLD,NASH,and NAFLD with fibrosis.Finally,we suggest possible areas for future research based on current gaps in knowledge.展开更多
基金This study was supported in part by National Institutes of Health(NIH)grant(K12 HD85036)University of California San Diego Altman Clinical and Translational Research Institute(ACTRI)/NIH grant(KL2TR001444)+14 种基金Pinnacle Research Award in Liver Diseases Grant(PNC22-159963)from the American Association for the Study of Liver Diseases Foundation(to Hartmann P)Deutsche Forschungsgemeinschaft(DFG,German Research Foundation)fellowship(LA 4286/1-1)the“Clinical and Translational Research Fellowship in Liver Disease”by the American Association for the Study of Liver Diseases(AASLD)Foundation(to Lang S)National Institutes of Health grants(R01 AA24726,R01 AA020703,U01 AA026939)Award Number BX004594 from the Biomedical Laboratory Research&Development Service of the VA Office of Research and DevelopmentBiocodex Microbiota Foundation Grant(to Schnabl B)services provided by NIH centers(P30 DK120515 and P50 AA011999)This study was also supported by the German Research Foundation(DFG)project(403224013-SFB 1382)(to Trebicka J)the German Federal Ministry of Education and Research(BMBF)for the DEEP-HCC project(to Trebicka J)the Hessian Ministry of Higher Education,Research and the Arts(HMWK)for the ENABLE and ACLF-I cluster projects(to Trebicka J)The MICROB-PREDICT(825694)DECISION(847949)GALAXY(668031)LIVERHOPE(731875)IHMCSA(964590)projects(all to Trebicka J)have received funding from the European Union’s Horizon 2020 research and innovation program.
文摘Background:Cirrhosis with acute decompensation(AD)and acute-on-chronic liver failure(ACLF)are characterized by high morbidity and mortality.Cytolysin,a toxin from Enterococcus faecalis(E.faecalis),is associated with mortality in alcohol-associated hepatitis(AH).It is unclear whether cytolysin also contributes to disease severity in AD and ACLF.Methods:We studied the role of fecal cytolysin in 78 cirrhotic patients with AD/ACLF.Bacterial DNA from fecal samples was extracted and real-time quantitative polymerase chain reaction(PCR)was performed.The association between fecal cytolysin and liver disease severity in cirrhosis with AD or ACLF was analyzed.Results:Fecal cytolysin and E.faecalis abundance did not predict chronic liver failure(CLIF-C)AD and ACLF scores.Presence of fecal cytolysin was not associated with other liver disease markers,including Fibrosis-4(FIB-4)index,‘Age,serum Bilirubin,INR,and serum Creatinine(ABIC)’score,Child-Pugh score,model for end-stage liver disease(MELD)nor MELD-Na scores in AD or ACLF patients.Conclusions:Fecal cytolysin does not predict disease severity in AD and ACLF patients.The predictive value of fecal cytolysin positivity for mortality appears to be restricted to AH.
基金Supported by National Institutes of Health(NIH),No.K12 HD85036University of California San Diego Altman Clinical and Translational Research Institute(ACTRI)/NIH,No.KL2TR001444+1 种基金Pinnacle Research Award in Liver Diseases from the American Association for the Study of Liver Diseases Foundation,No.#PNC22-159963the Pilot/Feasibility Grant of the San Diego Digestive Diseases Research Center(SDDRC),No.P30 DK120515(to P.H.)。
文摘Nonalcoholic fatty liver disease(NAFLD)is the leading cause of chronic liver disease worldwide among children and adolescents.It encompasses a spectrum of disease,from its mildest form of isolated steatosis,to nonalcoholic steatohepatitis(NASH)to liver fibrosis and cirrhosis,or end-stage liver disease.The early diagnosis of pediatric NAFLD is crucial in preventing disease progression and in improving outcomes.Currently,liver biopsy is the gold standard for diagnosing NAFLD.However,given its invasive nature,there has been significant interest in developing noninvasive methods that can be used as accurate alternatives.Here,we review noninvasive biomarkers in pediatric NAFLD,focusing primarily on the diagnostic accuracy of various biomarkers as measured by their area under the receiver operating characteristic,sensitivity,and specificity.We examine two major approaches to noninvasive biomarkers in children with NAFLD.First,the biological approach that quantifies serological biomarkers.This includes the study of individual circulating molecules as biomarkers as well as the use of composite algorithms derived from combinations of biomarkers.The second is a more physical approach that examines data measured through imaging techniques as noninvasive biomarkers for pediatric NAFLD.Each of these approaches was applied to children with NAFLD,NASH,and NAFLD with fibrosis.Finally,we suggest possible areas for future research based on current gaps in knowledge.