Progress in Biomarkers Related to Biliary Atresia

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Abstract

Biliary atresia (BA) is a congenital cholestatic disease that can seriously damage children’s liver function. It is one of the main reasons for liver transplantation in children. Early diagnosis of BA is crucial to the prognosis of patients, but there is still a lack of reliable non-invasive diagnostic methods. Additionally, as some children are in urgent need of liver transplantation, evaluating the stage of liver fibrosis and postoperative native liver survival in children with BA using a straightforward, efficient, and less traumatic method is a major focus of doctors. In recent years, an increasing number of BA-related biomarkers have been identified and have shown great potential in the following three aspects of clinical practice: diagnosis, evaluation of the stage of liver fibrosis, and prediction of native liver survival. This review focuses on the pathophysiological function and clinical application of three novel BA-related biomarkers, namely MMP-7, FGF-19, and M2BPGi. Furthermore, progress in well-known biomarkers of BA such as gamma-glutamyltransferase, circulating cytokines, and other potential biomarkers is discussed, aiming to provide a reference for clinical practice.

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A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C.

Chun-Tao Wai, Joel K. Greenson, Robert J. Fontana … (2003)

Information on the stage of liver fibrosis is essential in managing chronic hepatitis C (CHC) patients. However, most models for predicting liver fibrosis are complicated and separate formulas are needed to predict significant fibrosis and cirrhosis. The aim of our study was to construct one simple model consisting of routine laboratory data to predict both significant fibrosis and cirrhosis among patients with CHC. Consecutive treatment-naive CHC patients who underwent liver biopsy over a 25-month period were divided into 2 sequential cohorts: training set (n = 192) and validation set (n = 78). The best model for predicting both significant fibrosis (Ishak score > or = 3) and cirrhosis in the training set included platelets, aspartate aminotransferase (AST), and alkaline phosphatase with an area under ROC curves (AUC) of 0.82 and 0.92, respectively. A novel index, AST to platelet ratio index (APRI), was developed to amplify the opposing effects of liver fibrosis on AST and platelet count. The AUC of APRI for predicting significant fibrosis and cirrhosis were 0.80 and 0.89, respectively, in the training set. Using optimized cut-off values, significant fibrosis could be predicted accurately in 51% and cirrhosis in 81% of patients. The AUC of APRI for predicting significant fibrosis and cirrhosis in the validation set were 0.88 and 0.94, respectively. In conclusion, our study showed that a simple index using readily available laboratory results can identify CHC patients with significant fibrosis and cirrhosis with a high degree of accuracy. Application of this index may decrease the need for staging liver biopsy specimens among CHC patients.

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Extracellular matrix structure.

Achilleas Theocharis, Spyros Skandalis, Chrysostomi Gialeli … (2016)

Extracellular matrix (ECM) is a non-cellular three-dimensional macromolecular network composed of collagens, proteoglycans/glycosaminoglycans, elastin, fibronectin, laminins, and several other glycoproteins. Matrix components bind each other as well as cell adhesion receptors forming a complex network into which cells reside in all tissues and organs. Cell surface receptors transduce signals into cells from ECM, which regulate diverse cellular functions, such as survival, growth, migration, and differentiation, and are vital for maintaining normal homeostasis. ECM is a highly dynamic structural network that continuously undergoes remodeling mediated by several matrix-degrading enzymes during normal and pathological conditions. Deregulation of ECM composition and structure is associated with the development and progression of several pathologic conditions. This article emphasizes in the complex ECM structure as to provide a better understanding of its dynamic structural and functional multipotency. Where relevant, the implication of the various families of ECM macromolecules in health and disease is also presented.

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IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines.

Jochen Schmitz, Alexander Owyang, Elizabeth R. Oldham … (2005)

Cytokines of the interleukin-1 (IL-1) family, such as IL-1 alpha/beta and IL-18, have important functions in host defense, immune regulation, and inflammation. Insight into their biological functions has led to novel therapeutic approaches to treat human inflammatory diseases. Within the IL-1 family, IL-1 alpha/beta, IL-1Ra, and IL-18 have been matched to their respective receptor complexes and have been shown to have distinct biological functions. The most prominent orphan IL-1 receptor is ST 2. This receptor has been described as a negative regulator of Toll-like receptor-IL-1 receptor signaling, but it also functions as an important effector molecule of T helper type 2 responses. We report a member of the IL-1 family, IL-33, which mediates its biological effects via IL-1 receptor ST 2, activates NF-kappaB and MAP kinases, and drives production of T(H)2-associated cytokines from in vitro polarized T(H)2 cells. In vivo, IL-33 induces the expression of IL-4, IL-5, and IL-13 and leads to severe pathological changes in mucosal organs.

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Journal

Journal ID (nlm-ta): J Clin Transl Hepatol

Journal ID (iso-abbrev): J Clin Transl Hepatol

Journal ID (publisher-id): JCTH

Title: Journal of Clinical and Translational Hepatology

Publisher: XIA & HE Publishing Inc.

ISSN (Print): 2225-0719

ISSN (Electronic): 2310-8819

Publication date (Print): 28 March 2024

Publication date (Electronic): 30 January 2024

Volume: 12

Issue: 3

Pages: 305-315

Affiliations

Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, Shanghai, China

Author notes

[* ] Correspondence to: Shan Zheng, Department of Pediatric Surgery, Children’s Hospital of Fudan University, Shanghai Key Laboratory of Birth Defect, and Key Laboratory of Neonatal Disease, Ministry of Health, 399 Wan Yuan Road, Shanghai 201102, China. ORCID: https://orcid.org/0000-0002-9712-4573. Tel: +86-21-64932791, Fax: +86-21-64931901, E-mail: szheng@ 123456shmu.edu.cn

This study received financial support from Shanghai Municipal Key Clinical Specialty (No. shslczdzk05703), National Natural Science Foundation of China (No. 82270541, and No. 82201915), and Children’s National Medical Center (No. 2022LCKXJ06).

The authors have no conflict of interests related to this publication.

Conceptualization, writing of original draft, reviewing, and editing (FK); and conceptualization, reviewing, and editing (RD, GC, SS, YY, JJ, LM, HC, JZ, and SZ). All authors approved the final version of the manuscript.

Author information

Shan Zheng https://orcid.org/0000-0002-9712-4573

Article

Publisher ID: JCTH.2023.00260

DOI: 10.14218/JCTH.2023.00260

PMC ID: 10899875

PubMed ID: 38426193

SO-VID: 483cf35d-0ae6-4881-9905-99f8b20ccd32

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 4.0 International License (CC BY-NC 4.0), permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 30 May 2023

Date revision received : 12 December 2023

Date accepted : 2 January 2024

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Progress in Biomarkers Related to Biliary Atresia

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Journal of Circulating Biomarkers

Most cited references 119

A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C.

Extracellular matrix structure.

IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines.

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Cited by 2

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