Published online Dec 28, 2016. doi: 10.3748/wjg.v22.i48.10482
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
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.