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Bile acid indices as biomarkers for liver diseases Ⅱ: The bile acid score survival prognostic model

World Journal of Hepatology 2021年第5期13卷 543-556页

作者： Jawaher Abdullah Alamoudi Wenkuan Li Nagsen Gautam Marco Olivera jane meza Sandeep Mukherjee Yazen Alnouti Department of Pharmaceutical Sciences University of Nebraska Medical CenterOmahaNE 68198-6025United States Department of Pharmaceutical Sciences Princess Nourah Bint Abdulrahman UniversityRiyadh 11564Saudi Arabia Department of Internal Medicine University of Nebraska Medical CenterOmahaNE 68105United States Department of Biostatistics University of Nebraska Medical CenterOmahaNE 68198-4375United States Department of Internal Medicine Creighton University Medical CenterOmahaNE 68124United States

BACKGROUND Cholestatic liver diseases are characterized by an accumulation of toxic bile acids(BA)in the liver,blood and other tissues which lead to progressive liver injury and poor prognosis in *** To discover and validate prognostic biomarkers of cholestatic liver diseases based on the urinary BA *** We analyzed urine samples by liquid chromatography-tandem mass spectrometry and investigated the use of the urinary BA profile to develop survival models that can predict the prognosis of hepatobiliary *** urinary BA profile,a set of non-BA parameters,and the adverse events of liver transplant and/or death were monitored in 257 patients with cholestatic liver diseases for up to 7 *** BA profile was characterized by calculating BA indices,which quantify the composition,metabolism,hydrophilicity,formation of secondary BA,and toxicity of the BA *** have developed and validated the bile-acid score(BAS)model(a survival model based on BA indices)to predict the prognosis of cholestatic liver *** We have developed and validated a survival model based on BA(the BAS model)indices to predict the prognosis of cholestatic liver *** results demonstrate that the BAS model is more accurate and results in higher truepositive and true-negative prediction of death compared to both non-BAS and model for end-stage liver disease(MELD)*** 5-and 3-year survival probabilities markedly decreased as a function of ***,patients with high BAS had a 4-fold higher rate of death and lived for an average of 11 mo shorter than subjects with low *** increased risk of death with high vs low BAS was also 2-4-fold higher and the shortening of lifespan was 6-7-mo lower compared to MELD or ***,we have shown the use of BAS to predict the survival of patients with and without liver transplant(LT).Therefore,BAS could be used to define the most seriously ill patients,who need earlier intervention such as ***

关键词： Hepatobiliary diseases Bile acid indices Death Liver transplant Survival model Prognosis

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Bile acid indices as biomarkers for liver diseases I:Diagnostic markers

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World Journal of Hepatology 2021年第4期13卷 433-455页

作者： Jawaher Abdullah Alamoudi Wenkuan Li Nagsen Gautam Marco Olivera jane meza Sandeep Mukherjee Yazen Alnouti Department of Pharmaceutical Sciences College of PharmacyUniversity of Nebraska Medical CenterOmahaNE 68198United States Department of Pharmaceutical Sciences College of PharmacyPrincess Nourah Bint Abdulrahman UniversityRiyadh 11564Saudi Arabia Department of Internal Medicine College of MedicineUniversity of Nebraska Medical CenterOmahaNE 68198United States Department of Biostatistics College of Public HealthUniversity of Nebraska Medical CenterOmahaNE 68198United States Department of Internal Medicine College of MedicineCreighton University Medical CenterOmahaNE 68124United States

BACKGROUND Hepatobiliary diseases result in the accumulation of toxic bile acids(BA)in the liver,blood,and other tissues which may contribute to an unfavorable *** To discover and validate diagnostic biomarkers of cholestatic liver diseases based on the urinary BA *** We analyzed urine samples by liquid chromatography-tandem mass spectrometry and compared the urinary BA profile between 300 patients with hepatobiliary diseases vs 103 healthy controls by statistical *** BA profile was characterized using BA indices,which quantifies the composition,metabolism,hydrophilicity,and toxicity of the BA *** indices have much lower interand intra-individual variability compared to absolute concentrations of *** addition,BA indices demonstrate high area under the receiver operating characteristic curves,and changes of BA indices are associated with the risk of having a liver disease,which demonstrates their use as diagnostic biomarkers for cholestatic liver *** Total and individual BA concentrations were higher in all *** percentage of secondary BA(lithocholic acid and deoxycholic acid)was significantly lower,while the percentage of primary BA(chenodeoxycholic acid,cholic acid,and hyocholic acid)was markedly higher in patients compared to *** addition,the percentage of taurine-amidation was higher in patients than *** increase in the non-12α-OH BA was more profound than 12α-OH BA(cholic acid and deoxycholic acid)causing a decrease in the 12α-OH/non-12α-OH ratio in *** trend was stronger in patients with more advanced liver diseases as reflected by the model for end-stage liver disease score and the presence of hepatic *** percentage of sulfation was also higher in patients with more severe forms of liver *** BA indices have much lower inter-and intra-individual variability compared to absolute BA concentrations and changes of BA indices are associated with the

关键词： Hepatobiliary diseases Bile acids Bile acid indices Diagnosis Biomarker Liver diseases

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