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Processes (Basel). 2018 Aug;6(8). doi: 10.3390/pr6080115. Epub 2018 Aug 04.

Modeling the Dynamics of Human Liver Failure Post Liver Resection.

Processes (Basel, Switzerland)

Babita K Verma, Pushpavanam Subramaniam, Rajanikanth Vadigepalli

Affiliations

  1. Daniel Baugh Institute for Functional Genomics/Computational Biology, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
  2. Department of Chemical Engineering, Indian Institute of Technology-Madras, Chennai 600036, India.

PMID: 31131255 PMCID: PMC6534166 DOI: 10.3390/pr6080115

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.

Keywords: cell death; dynamic modeling; liver failure; liver regeneration; liver resection; virtual patient

Conflict of interest statement

Conflicts of Interest: The authors declare no conflict of interest. The funding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing

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