Modeling the Dynamics of Human Liver Failure Post Liver Resection

Abstract

Liver resection is an important clinical intervention to treat liver disease. Following liver resection, patients exhibit a wide range of outcomes including normal recovery, suppressed recovery, or liver failure, depending on the regenerative capacity of the remnant liver. The objective of this work is to study the distinct patient outcomes post hepatectomy and determine the processes that are accountable for liver failure. Our model based approach shows that cell death is one of the important processes but not the sole controlling process responsible for liver failure. Additionally, our simulations showed wide variation in the timescale of liver failure that is consistent with the clinically observed timescales of post hepatectomy liver failure scenarios. Liver failure can take place either instantaneously or after a certain delay. We analyzed a virtual patient cohort and concluded that remnant liver fraction is a key regulator of the timescale of liver failure, with higher remnant liver fraction leading to longer time delay prior to failure. Our results suggest that, for a given remnant liver fraction, modulating a combination of cell death controlling parameters and metabolic load may help shift the clinical outcome away from post hepatectomy liver failure towards normal recovery.