Background: Biliary atresia (BA) is a rare fatal liver disease in children, and the aim of this study was to develop a method to diagnose BA early.
Methods: We determined serum levels of matrix metalloproteinase-7 (MMP-7), the results of 13 liver tests, and the levels of 20 bile acids, and integrated computational models were constructed to diagnose BA.
Results: Our findings demonstrated that MMP-7 expression levels, as well as the results of four liver tests and levels of ten bile acids, were significantly different between 86 BA and 59 non-BA patients (P < 0.05). The computational prediction model revealed that MMP-7 levels alone had a higher predictive accuracy [area under the receiver operating characteristic curve (AUC) = 0.966, 95% confidence interval (CI): 0.942, 0.989] than liver test results and bile acid levels. The AUC was 0.890 (95% CI 0.837, 0.943) for liver test results and 0.825 (95% CI 0.758, 0.892) for bile acid levels. Furthermore, bile levels had a higher contribution to enhancing the predictive accuracy of MMP-7 levels (AUC = 0.976, 95% CI 0.953, 1.000) than liver test results. The AUC was 0.983 (95% CI 0.962, 1.000) for MMP-7 levels combined with liver test results and bile acid levels. In addition, we found that MMP-7 levels were highly correlated with gamma-glutamyl transferase levels and the liver fibrosis score.
Conclusion: The innovative integrated models based on a large number of indicators provide a noninvasive and cost-effective approach for accurately diagnosing BA in children. Video Abstract (MP4 142103 KB).
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http://dx.doi.org/10.1007/s12519-023-00779-7 | DOI Listing |
Arch Toxicol
December 2024
Division of Toxicology, Wageningen University and Research, Stippeneng 4, 6708 WE, Wageningen, The Netherlands.
Systemic bile acid homeostasis plays an important role in human health. In this study, a physiologically based kinetic (PBK) model that includes microbial bile acid deconjugation and intestinal bile acid reuptake via the apical sodium-dependent bile acid transporter (ASBT) was applied to predict the systemic plasma bile acid concentrations in human upon oral treatment with the antibiotic tobramycin. Tobramycin was previously shown to inhibit intestinal deconjugation and reuptake of bile acids and to affect bile acid homeostasis upon oral exposure of rats.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Isoniazid and rifampicin co-therapy are the main causes of anti-tuberculosis drug-induced liver injury (ATB-DILI) and acute liver failure, seriously threatening human health. However, its pathophysiology is not fully elucidated. Growing evidences have shown that fibroblast growth factors (FGFs) play a critical role in diverse aspects of liver pathophysiology.
View Article and Find Full Text PDFCancer Genomics Proteomics
December 2024
Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand;
Background/aim: Cholangiocarcinoma (CCA) is an aggressive hepatobiliary malignancy characterized by genomic heterogeneity. KRAS mutations play a significant role in influencing patient prognosis and guiding therapeutic decision-making. This study aimed to determine the prevalence and prognostic significance of KRAS mutations in CCA, asses the detection of KRAS G12/G13 mutations in plasma cell-free DNA (cfDNA), and evaluate the prognostic value of KRAS G12/G13 mutant allele frequency (MAF) in cfDNA in relation to clinicopathological data and patient survival.
View Article and Find Full Text PDFAm J Pathol
December 2024
Department of Microbiology and Immunology, Virginia Commonwealth University and Richmond VA Medical Center, Richmond, Virginia; Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, School of Medicine, Virginia Commonwealth University, Richmond, Virginia. Electronic address:
Cholangiocarcinoma (CCA) is a rare but highly malignant carcinoma of bile duct epithelial cells with a poor prognosis. The major risk factors of CCA carcinogenesis and progression are cholestatic liver diseases. The key feature of primary sclerosing cholangitis and primary biliary cholangitis is chronic cholestasis, which means a slowdown of hepatocyte secretion of biliary lipids and metabolites into bile as well as a slowdown of enterohepatic circulation (bile acid recirculation) of bile acids with dysbiosis of the gut microbiome, which was shown to lead to enterohepatic recirculation and an increase of toxic secondary bile acids.
View Article and Find Full Text PDFMetabolites
December 2024
Department of Microbiology, Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
: This systematic review evaluates the effectiveness of fecal microbiota transplantation (FMT) in treating infection (CDI) in mouse models using a metabolomics-based approach. : A comprehensive search was conducted in three databases (PubMed, Scopus, Google Scholar) from 10 April 2024 to 17 June 2024. Out of the 460 research studies reviewed and subjected to exclusion criteria, only 5 studies met all the inclusion criteria and were analyzed.
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