The Role of Oxygen Intake and Liver Enzyme on The Dynamics of Damaged Hepatocytes}: \\ Implications to Ischaemic Liver Injury via A Mathematical Model.
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. Unfortunately, mechanism that causes IH are often not well understood, making it difficult to diagnose or accurately quantify the patterns of related biomakers. 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 livers response to IH is necessary to aid in its diagnosis, measurement and improve outcomes. 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. 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.