Does pressure cause liver cirrhosis? The sinusoidal pressure hypothesis

Table 3 Direct clinical consequences of sinusoidal pressure hypothesis

Potential clinical impact of SPH	Ref.
1. Therapeutic effects of pressure lowering drugs. Optimization of timing, patient selection, dosage and duration. Risk balancing of side affects to other organs (kidneys, arterial underfilling).	[77]
2. Long-term therapy with diuretics as causal/fibrosis-blocking treatment.
3. Testing of an optimized risk stratification of cirrhotics on outcome according to liver stiffness (M1 vs M2 type, see paragraph "Important consequences of SPH and critical discussion", point 3) in addition to liver function scores such as Child-Pugh score or MELD score.	[25]
4. Liver disease as cause and consequence in the systemic context with other organs such as kidney and heart failure.	[57]
5. Test whether GGT elevation and an AST/ALT ratio > 1 at low AST and ALT levels is related with arterialization of liver and, consequently, with manifestation of liver cirrhosis.
6. Study water retention in cirrhosis, pregnancy, renal and heart failure and its consequences on hydrostatic SP.	[82]
7. Implementation of osmotic stress, water channels (aquaporines) and transporters.
8. Therapeutic approaches to lower SP by targeting mechano-signaling: mechanic conditioning and pharmacotherapy acting on mechano-signaling.
9. Role of biomembrane composition, lipid composition and potential protective role of steatosis on pressure-induced fibrosis.
10. Non-invasive LS measurements to monitor and optimize treatment of liver diseases.
11. Implementation of liquid physics to better understand the dynamic component of SP and its role on fibrosis progression.
12. Understanding of pulse wave energy and its consequences on the liver tissue.

ALT: Alanine aminotransferase; AST: Asparagin aminotransferase; GGT: Gamma-glutamyl transpeptidase; LS: Liver stiffness; SP: Sinusoidal pressure; SPH: Sinusoidal pressure hypothesis.