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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pharmacol Ther. Aug 6, 2015; 6(3): 32-58
Published online Aug 6, 2015. doi: 10.4292/wjgpt.v6.i3.32
Primary biliary cirrhosis: From bench to bedside
Elias Kouroumalis, George Notas
Elias Kouroumalis, Department of Gastroenterogy and Hepatology, University of Crete Medical School, 71003 Heraklion, Crete, Greece
George Notas, Department of Experimental Endocrinology, University of Crete Medical School, 71003 Heraklion, Crete, Greece
George Notas, Institute of Applied Computational Mathematics, Foundation of Research and Technology Hellas (IACM-FORTH), 70013 Heraklion, Crete, Greece
Author contributions: Kouroumalis E and Notas G contributed to this paper.
Conflict-of-interest statement: None.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Elias Kouroumalis, MD, PhD, Professor, Department of Gastroenterology and Hepatology, University of Crete Medical School, PO BOX 2208, 71003 Heraklion, Crete, Greece. kouroum@med.uoc.gr
Telephone: +30-2810-392355 Fax: +30-2810-542085
Received: July 9, 2014
Peer-review started: July 9, 2014
First decision: October 28, 2014
Revised: April 21, 2015
Accepted: May 16, 2015
Article in press: May 18, 2015
Published online: August 6, 2015
Processing time: 394 Days and 21.9 Hours
Abstract

Primary biliary cirrhosis (PBC) is a chronic non-suppurative destructive intrahepatic cholangitis leading to cirrhosis after a protractive non cirrhotic stage. The etiology and pathogenesis are largely unknown and autoimmne mechanisms have been implicated to explain the pathological lesions. Many epitopes and autoantigens have been reported as crucial in the pathophysiology of the disease and T and B cells abnormalities have been described, the exact pathways leading to the destruction of small intrahepatic ductules are mostly speculative. In this review we examined the various epidemiologal and geoepidemiological data as well as the complex pathogenetic aspects of this disease, focusing on recent in vivo and in vitro studies in this field. Initiation and progression of PBC is believed to be a multifactorial process with strong infuences from the patient’s genetic background and by various environmental factors. The role of innate and adaptive immunity, including cytokines, chemokines, macrophages and the involvement of apoptosis and reactive oxygen species are outlined in detailed. The current pathogenetic aspects are presented and a novel pathogenetic theory unifying the accumulated clinical information with in vitro and in vivo data is formulated. A review of clinical manifestations and immunological and pathological diagnosis was presented. Treatment modalities, including the multiple mechanisms of action of ursodeoxycholate were finally discussed.

Keywords: Primary biliary cirrhosis, Innate immunity, Adaptive immunity, Ursodeoxycholate, Chemokines, Macrophages, Cytokines

Core tip: Primary biliary cirrhosis (PBC) is a chronic non-suppurative destructive intrahepatic cholangitis leading to cirrhosis of largely unknown pathophysiology. We examined the epidemiological and geoepidemiological data as well as the pathogenetic aspects of PBC. A novel pathogenetic theory unifying the accumulated clinical information with in vitro and in vivo data is formulated. A review of clinical manifestations and immunological and pathological diagnosis was presented. Treatment modalities, including the multiple mechanisms of action of ursodeoxycholate are discussed.