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World J Gastroenterol. Jun 7, 2022; 28(21): 2291-2301
Published online Jun 7, 2022. doi: 10.3748/wjg.v28.i21.2291
Serological biomarkers for management of primary sclerosing cholangitis
David Tornai, Peter Laszlo Ven, Peter Laszlo Lakatos, Maria Papp
David Tornai, Maria Papp, Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen H-4032, Hajdu-Bihar, Hungary
David Tornai, Maria Papp, European Reference Network on Hepatological Diseases, ERN RARE-LIVER, Debrecen H-4032, Hajdu-Bihar, Hungary
Peter Laszlo Ven, The First Department of Medicine, Division of Gastroenterology, University of Pécs, Pécs H-7624, Baranya, Hungary
Peter Laszlo Ven, Kálmán Laki Doctoral School of Biomedical and Clinical Sciences, Faculty of Medicine, University of Debrecen, Debrecen H-4032, Hajdu-Bihar, Hungary
Peter Laszlo Lakatos, Division of Gastroenterology, McGill University Health Centre, Montreal QC H4A 3J1, Quebec, Canada
Peter Laszlo Lakatos, The First Department of Medicine, Semmelweis University, Budapest H-1083, Pest, Hungary
Author contributions: Tornai D and Ven PL performed the literature review; Tornai D wrote the manuscript; Papp M and Lakatos PL supervised the work and provided expert insights; all authors have read and approved the final manuscript.
Supported by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, No. 138041; and the EFOP projects co-financed by the European Union and the European Social Fund, No. EFOP-3.6.1-16-2016-00022.
Conflict-of-interest statement: There are no conflicts of interest to report.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Maria Papp, DSc, FEBG, MD, PhD, Full Professor, Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, Debrecen H-4032, Hajdu-Bihar, Hungary. papp.maria@med.unideb.hu
Received: December 13, 2021
Peer-review started: December 13, 2021
First decision: January 23, 2022
Revised: February 1, 2022
Accepted: April 25, 2022
Article in press: April 25, 2022
Published online: June 7, 2022
Abstract

Clinical manifestations and progression of primary sclerosing cholangitis (PSC) are heterogeneous, and its pathogenesis is poorly understood. The importance of gut-liver interactions in the pathogenesis has been clinically confirmed and highlighted in different theories. Recent advances regarding biomarkers of biliary-gut crosstalk may help to identify clinically relevant PSC subgroups assisting everyday clinical work-up (e.g., diagnosis, disease stratification, or surveillance) and the exploration of potential therapeutic targets. Alkaline phosphatase produced by the biliary epithelium is consistently associated with prognosis. However, its level shows natural fluctuation limiting its use in individual patients. Inflammatory, cell activation, and tissue remodeling markers have been reported to predict clinical outcome. Elevated immunoglobulin (Ig) G4 level is associated with a shorter transplantation-free survival. IgG type atypical perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCAs) are non-specific markers of various autoimmune liver diseases and may reflect an abnormal B-cell response to gut microbial antigens. IgG type atypical P-ANCA identifies PSC patients with particular clinical and genetic (for human leukocyte antigens) characteristics. The presence of IgA type anti-F-actin antibody (AAA) may predict a progressive disease course, and it is associated with enhanced mucosal immune response to various microbial antigens and enterocyte damage. IgA type anti-glycoprotein 2 (GP2) antibodies identify patients with a severe disease phenotype and poor survival due to enhanced fibrogenesis or development of cholangiocarcinoma. Elevated soluble vascular adhesion protein-1 (sVAP-1) level is associated with adverse disease outcomes in PSC. High sVAP-1 levels correlate with mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expression in the liver that contributes to gut activated T-cell homing to the hepatobiliary tract. In the present paper, we review the evidence on these possible serological markers that could potentially help address the unmet clinical needs in PSC.

Keywords: Primary sclerosing cholangitis, Hepatobiliary, Serological biomarker, Immunoglobulin, Inflammatory, Tissue remodeling

Core Tip: Recent advances in biomarker research may help clinicians identify relevant subgroups of primary sclerosing cholangitis (PSC) and assist everyday clinical work-up. However, a diagnostic biomarker is still an unmet need. On the other hand, several biomarkers have been reported to predict outcome in PSC; however, most of them have not been validated by subsequent studies. The IgA type anti-glycoprotein 2 antibody is the first one to be supported by a satisfactory number of clinical studies and could be incorporated into clinical practice. These discoveries also reveal different aspects of PSC providing with potential therapeutic targets.