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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2016; 22(18): 4427-4437
Published online May 14, 2016. doi: 10.3748/wjg.v22.i18.4427
Thrombin activation and liver inflammation in advanced hepatitis C virus infection
Emilio González-Reimers, Geraldine Quintero-Platt, Candelaria Martín-González, Onán Pérez-Hernández, Lucía Romero-Acevedo, Francisco Santolaria-Fernández
Emilio González-Reimers, Geraldine Quintero-Platt, Candelaria Martín-González, Onán Pérez-Hernández, Lucía Romero-Acevedo, Francisco Santolaria-Fernández, Servicio de Medicina Interna, Hospital Universitario de Canarias, Universidad de La Laguna, Tenerife, 38320 Canary Islands, Spain
Author contributions: González-Reimers E, Martín-González C, Pérez-Hernández O, Romero-Acevedo L and Quintero-Platt G made the review and drafted the manuscript; and Santolaria-Fernández F revised it.
Conflict-of-interest statement: The authors declare that there are no conflicts of interest regarding this manuscript. They also declare that they have not received any funding for this study.
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: Emilio González-Reimers, MD, PhD, Servicio de Medicina Interna, Hospital Universitario de Canarias, Universidad de La Laguna, Ofra s/n, San Cristóbal de La Laguna, Tenerife, 38320 Canary Islands, Spain. egonrey@ull.es
Telephone: +34-922-678600
Received: February 25, 2016
Peer-review started: February 25, 2016
First decision: March 21, 2016
Revised: March 30, 2016
Accepted: April 15, 2016
Article in press: April 15, 2016
Published online: May 14, 2016
Processing time: 69 Days and 5.9 Hours
Abstract

Hepatitis C virus (HCV) infection is associated with increased thrombotic risk. Several mechanisms are involved including direct endothelial damage by the HCV virus, with activation of tissue factor, altered fibrinolysis and increased platelet aggregation and activation. In advanced stages, chronic HCV infection may evolve to liver cirrhosis, a condition in which alterations in the portal microcirculation may also ultimately lead to thrombin activation, platelet aggregation, and clot formation. Therefore in advanced HCV liver disease there is an increased prevalence of thrombotic phenomena in portal vein radicles. Increased thrombin formation may activate hepatic stellate cells and promote liver fibrosis. In addition, ischemic changes derived from vascular occlusion by microthrombi favor the so called parenchymal extinction, a process that promotes collapse of hepatocytes and the formation of gross fibrous tracts. These reasons may explain why advanced HCV infection may evolve more rapidly to end-stage liver disease than other forms of cirrhosis.

Keywords: Coagulation; Liver cirrhosis; Hepatitis C virus; Fibrogenesis; Parenchymal extinction; Portal thrombosis; Protein C

Core tip: Liver cirrhosis may be considered a prothrombotic condition despite it being associated with a low platelet count and deranged synthesis of clotting factors. When hepatitis C virus (HCV) is the etiological factor of liver cirrhosis, intrahepatic coagulation may be enhanced by several direct actions of HCV on the clotting system, platelet aggregation, and altered anticoagulation. The excessive thrombin generation may be related to increased fibrogenesis both by a direct effect of thrombin on hepatic stellate cells and fibrosis related to ischemic parenchymal extinction.