Markov Chains Analyzing Dataset of Patients with Metabolic Associated Fatty Liver Disease
Authors: Attia Iman M. 
Published: July 2022

Abstract
The prevalence of obesity and type 2 diabetes has reached epidemic levels that parallel the rates of the widely distributed non-alcoholic fatty liver disease (NAFLD). Nearly one billion people worldwide suffered from NAFLD. The estimated annual medical costs for NAFLD exceed €35 billion in four large European countries (the United Kingdom, France, Germany, and Italy) and $100 billion in the United States. According to the American Association for the study of liver disease, NAFLD requires the presence of hepatic steatosis in more than 5 % of hepatocytes detected by histology or imaging with little consumption of alcohol and exclusion of other causes of chronic liver diseases.The risk factors for NAFLD are age>45, males are more susceptible than females, ethnicity; the Hispanics have more prevalent rates than the whites who are more susceptible than the blacks, ingestion of high fat and high cholesterol diet, genetic backgrounds like patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene which is most prevalent in Hispanics followed by non-Hispanics whites and African Americans, and features of metabolic syndrome.The newly proposed name is metabolic associated fatty liver disease (MAFLD). This new definition requires evidence of hepatic steatosis as previously mentioned plus one of three features: obesity or overweight (BMI > 25 kg/m2 in white and > 23 kg/m2 in Asian Individuals), type 2 diabetes, or lean or normal weight with evidence of metabolic dysregulation. For the definition of metabolic dysregulation , at least two risk metabolic risk factors should be present. These factors are waist circumference ≥ 102cm for males and ≥ 88cm for females in the western countries, while for the Asian and Eastern males and female , it is ≥ 90 cm and ≥ 80 cm respectively, prediabetes, homeostasis model assessment of insulin resistance (HOMA-IR) ≥ 2.5 ,elevated high-sensitive serum C-reactive protein(CRP) denoting inflammation, elevated blood pressure or specific drug treatment, decreased high-density lipoprotein (HDL) cholesterol levels, and increased plasma triglycerides or drug treatment. The pathogenesis of this disease process can be explained by the “two-hit theory” which is updated to the “multiple or parallel hit theory”. The first hit is initiated by liver fat content exceeding five percent of the total hepatocytes and concomitant insulin resistance. This fatty liver is more vulnerable to the second hit, inflammation, and necrosis (death of cells). This inflammation is called steatohepatitis which stimulates fibrosis. Other hits that augment this steatohepatitis are the interactions of the genetic and environmental factors and the cross-talk between different organs and tissues like the adipose tissue, the pancreas, the gut (microbiota), and the liver. Liver biopsy, although invasive and has some limitations like sampling error, hospital admission, elevated costs, and obseobserver-dependents the gold standard method for diagnosis. Rigorous control of risk factors with lifestyle modifications by reducing the caloric intake and exercises can protect the liver. The newly emerging anti-fibrotic and anti-inflammatory drugs are promising to reduce the histo-pathological picture of the disease.