©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 28, 2016; 22(48): 10482-10501
Published online Dec 28, 2016. doi: 10.3748/wjg.v22.i48.10482
Published online Dec 28, 2016. doi: 10.3748/wjg.v22.i48.10482
Does pressure cause liver cirrhosis? The sinusoidal pressure hypothesis
Sebastian Mueller, Department of Medicine and Center for Alcohol Research, Salem Medical Center, University of Heidelberg, Zeppelinstr, 69121 Heidelberg, Germany
Author contributions: Mueller S solely contributed to the conception and design, writing the paper, critical reading and final approval.
Conflict-of-interest statement: No conflict of interest to report.
Correspondence to: Sebastian Mueller, MD, PhD, Professor of Medicine, Vice Head, Co-Director, Department of Medicine and Center for Alcohol Research, Salem Medical Center, University of Heidelberg, Zeppelinstraße 11 - 33, 69121 Heidelberg, Germany. sebastian.mueller@urz.uni-heidelberg.de
Telephone: +49-6221-483210 Fax: +49-6221-484494
Received: July 27, 2016
Peer-review started: August 1, 2016
First decision: September 28, 2016
Revised: October 10, 2016
Accepted: November 23, 2016
Article in press: November 28, 2016
Published online: December 28, 2016
Processing time: 151 Days and 23.1 Hours
Peer-review started: August 1, 2016
First decision: September 28, 2016
Revised: October 10, 2016
Accepted: November 23, 2016
Article in press: November 28, 2016
Published online: December 28, 2016
Processing time: 151 Days and 23.1 Hours
Core Tip
Core tip: This paper introduces the sinusoidal pressure hypothesis, which identifies an elevation of sinusoidal pressure (SP) as cause of fibrosis/cirrhosis. Accordingly, elevated SP is the major upstream event that initiates fibrosis progression via biomechanic signaling by stretching of perisinusoidal cells. Fibrosis progression is determined by the degree and time of elevated SP. The cirrhotic extracellular matrix eventually matches the degree of pressure. Arterialization of the stiff cirrhotic liver represents the final self-perpetuating key event exposing the low-pressure-organ to pathologically high pressures. It also defines the “point of no return” where fibrosis progression becomes irreversible.