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The Role of Oxygen Intake and Liver Enzyme on The Dynamics of Damaged Hepatocytes}: \\ Implications to Ischaemic Liver Injury via A Mathematical Model.

By Aditi Ghosh, Claire Onsager, Leon Arriola, Andrew Mason, William Lee, Anuj Mubayi

Posted 11 Mar 2020
bioRxiv DOI: 10.1101/2020.03.11.987594

Ischaemic Hepatitis (IH) or Hypoxic Hepatitis (HH) also known as centrilobular liver cell necrosis is an acute liver injury characterized by a rapid increase in serum aminotransferase.  The liver injury typically results from another underlying medical conditions like cardiac failure, respiratory failure and septic shock in which the liver becomes damaged due to deprivation of either blood or oxygen. IH  is a  potentially lethal condition which is often preventable if diagnosed properly. {\em Unfortunately, mechanism that causes IH are often  not well understood, making it difficult to diagnose or accurately quantify the patterns of related biomarkers}. In most cases, currently the only way to determine a case of IH (i.e., to  diagnose it) is to rule out all other possible conditions for other liver injuries. A better understanding of the liver's response to IH is necessary to aid in its  diagnosis, measurement and improve outcomes. {\bf The goal of this study, is to identify mechanisms that can alter a few associated biomarkers for reducing density of damaged hepatocytes, and thus reduce chances of IH}. To this end, we develop a mathematical model capturing dynamics of hepatocytes in the liver through the rise and fall of associated liver enzymes aspartate transaminase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) related to condition of IH. %It studies liver cell death in response to IH caused by chronic heart failure and cardiovascular shock.   The  model analysis provides a novel approach to  predict the level of biomarkers given variations in the systemic oxygen in the body. Using IH patient data in US, novel model parameters are described and then estimated for the first time to capture real time dynamics of hepatocytes in the presence and absence of IH condition. Different scenarios of patient conditions  were also analyzed and validated using empirical information. This study and its results may allow physicians to estimate the extent of liver damage in a IH patient based on their enzyme levels and receive faster treatment on real time basis.

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