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World J Gastroenterol. Sep 7, 2018; 24(33): 3738-3748
Published online Sep 7, 2018. doi: 10.3748/wjg.v24.i33.3738
Antiangiogenic therapy for portal hypertension in liver cirrhosis: Current progress and perspectives
Dmitry Victorovich Garbuzenko, Nikolay Olegovich Arefyev, Evgeniy Leonidovich Kazachkov
Dmitry Victorovich Garbuzenko, Department of Faculty Surgery, South Ural State Medical University, Chelyabinsk 454092, Russia
Nikolay Olegovich Arefyev, Evgeniy Leonidovich Kazachkov, Department of Pathological Anatomy and Forensic Medicine, South Ural State Medical University, Chelyabinsk 454092, Russia
Author contributions: Garbuzenko DV contributed to the conception, design, acquisition, analysis, interpretation of data, wrote the manuscript and approved the final version; Arefyev NO contributed to analysis of data, wrote and revised the manuscript, generated the figures and tables, and approved the final version; Kazachkov EL contributed to analysis of data, revised the manuscript, and approved the final version.
Supported by RFBR according to the research project, No. 18-315-00434.
Conflict-of-interest statement: Dr. Arefyev reports a grant from RFBR (Russian Foundation for Basic Research), during the conduct of the study. The information included in this manuscript is not related to the interests of RFBR. Prof. Garbuzenko and Prof. Kazachkov have nothing to disclose.
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: Dmitry Victorovich Garbuzenko, MD, PhD, Professor, Department of Faculty Surgery, South Ural State Medical University, PO Box 12317, Chelyabinsk 454080, Russia. garb@inbox.ru
Telephone: +7-909-7459826 Fax: +7-351-2687772
Received: May 27, 2018
Peer-review started: May 27, 2018
First decision: July 4, 2018
Revised: July 9, 2018
Accepted: July 16, 2018
Article in press: July 16, 2018
Published online: September 7, 2018
Processing time: 103 Days and 11 Hours
Abstract

Developing medicines for hemodynamic disorders that are characteristic of cirrhosis of the liver is a relevant problem in modern hepatology. The increase in hepatic vascular resistance to portal blood flow and subsequent hyperdynamic circulation underlie portal hypertension (PH) and promote its progression, despite the formation of portosystemic collaterals. Angiogenesis and vascular bed restructurization play an important role in PH pathogenesis as well. In this regard, strategic directions in the therapy for PH in cirrhosis include selectively decreasing hepatic vascular resistance while preserving or increasing portal blood flow, and correcting hyperdynamic circulation and pathological angiogenesis. The aim of this review is to describe the mechanisms of angiogenesis in PH and the methods of antiangiogenic therapy. The PubMed database, the Google Scholar retrieval system, and the reference lists from related articles were used to search for relevant publications. Articles corresponding to the aim of the review were selected for 2000-2017 using the keywords: “liver cirrhosis”, “portal hypertension”, “pathogenesis”, “angiogenesis”, and “antiangiogenic therapy”. Antiangiogenic therapy for PH was the inclusion criterion. In this review, we have described angiogenesis inhibitors and their mechanism of action in relation to PH. Although most of them were studied only in animal experiments, this selective therapy for abnormally growing newly formed vessels is pathogenetically reasonable to treat PH and associated complications.

Keywords: Liver cirrhosis; Portal hypertension; Pathogenesis; Angiogenesis; Antiangiogenic therapy

Core tip: This review describes the role of angiogenesis in the pathogenesis of portal hypertension in liver cirrhosis and the prospects of antiangiogenic therapy. The analysis of the data showed that angiogenesis plays an important role in the pathogenesis of cirrhosis and accompanies portal hypertension, underlying its development and causing related complications. Although most of angiogenesis inhibitors were studied only in animal experiments, this selective therapy for abnormally growing newly formed vessels is pathogenetically reasonable to treat portal hypertension and associated complications.