The Sinusoidal Pressure Hypothesis

The sinusoidal pressure hypothesis proposes that elevated sinusoidal pressure is not merely a consequence of cirrhosis but may act upstream as a driver of fibrogenesis.

The hypothesis emerged from studies showing that liver stiffness changes immediately with venous, biliary and arterial pressure. It extends these observations into a mechanistic model in which persistent pressure generates biomechanical stretch within the perisinusoidal compartment, activates matrix-producing pathways and promotes fibrosis.

The model separates two phases: initiation, in which elevated sinusoidal pressure triggers mechano-signalling, and perpetuation, in which vascular remodeling and arterialization sustain the pressure load. It provides a unifying physical framework for otherwise diverse causes of chronic liver injury.

Core concept of the sinusoidal pressure hypothesis: persistent sinusoidal pressure is translated into mechanical forces that promote fibrogenesis.

Conceptual transition from reversible pressure-related stiffness to persistent matrix deposition and self-perpetuating cirrhosis.

Selected publications

Does pressure cause liver cirrhosis? The sinusoidal pressure hypothesis. Mueller S. World J Gastroenterol. 2016;22(48):10482–10501.
Liver stiffness is directly influenced by central venous pressure. Millonig G et al. J Hepatol. 2010;52(2):206–210.
Arterial pressure suffices to increase liver stiffness. Piecha F et al. Am J Physiol Gastrointest Liver Physiol. 2016;311(5):G945–G953.