Portal Venous Remodeling Determines the Pattern of Cirrhosis Decompensation: A Systems Analysis

Abstract

Background and rationale for the study As liver disease progresses, scarring results in worsening hemodynamics ultimately culminating in portal hypertension. This process has classically been quantified via the Porto-Systemic pressure Gradient (PSG) which is clinically estimated by Hepatic Venous Pressure Gradient (HVPG), however PSG alone does not predict a given patient's clinical trajectory with regards to Baveno stage of cirrhosis. We hypothesize that a patient's 'PSG-sensitivity' to venous remodeling could explain disparate disease trajectories. We created a computational model of the portal system in the context of worsening liver disease informed by physiologic measurements from the field of portal hypertension. We simulated progression of clinical complications, HVPG and transjugular intrahepatic portosystemic shunt (TIPS) placement while only varying a patient's likelihood of portal venous remodeling. Main Results Our results unify hemodynamics, venous remodeling, and the clinical progression of liver disease into a mathematically consistent model of portal hypertension. We find that by varying how 'sensitive' patients are to create venous collaterals with rising PSG we can explain variation in patterns of decompensation for patients with liver disease. Specifically, we find that patients who have higher proportions of portosystemic shunting earlier in disease have an attenuated rise in HVPG, delayed onset of ascites, and less hemodynamic shifting after TIPS placement. Conclusion This paper builds a computational model of portal hypertension which supports that patient level differences in venous remodeling may explain disparate clinical trajectories of disease.