Liver Metabolism and Fatty Liver Disease PDF

Preface

LIVER METABOLISM AND FATTY LIVER DISEASE

Nonalcoholic fatty liver disease (NAFLD) comprises a spectrum of hepatic pathology, ranging from simple steatosis (SS), in which there is an increase of fat accumulation in hepatocytes, to nonalcoholic steatohepatitis (NASH), to cirrhosis. Primary NAFLD is associated with obesity, insulin resistance and metabolic syndrome, diabetes, and dyslipidemia. Secondary NAFLD is associated with all forms of liver damage including viral infections, autoimmune and hereditary diseases, drugs, toxins, and nutrition (parenteral nutrition, vitamin B12/folic acid deficiency, etc.). NASH is a progressive lesion in which steatosis is accompanied by hepatocyte injury and death as well as by hepatic infiltration of inflammatory cells. NASH-related liver damage often triggers liver fibrosis. In severe cases, NASH may progress to cirrhosis and possibly to hepatocellular carcinoma. NAFLD is one of the most common liver diseases worldwide affecting all racial, ethnic, and age groups without sex predilection. The prevalence of NAFLD is between 15% and 45% of the general population, whereas NASH affects about 3% of the lean population (those weighing no more than 110% of their ideal body weight), 19% of the obese population, and almost half of morbidly obese people.

It has become evident that progression from SS to NASH is not just a consequence of free fatty acid (FFA)–derived triglyceride (TG) accumulation in hepatocytes but, rather, the inadequate adaptation of the cells to toxic lipid–derived metabolites. Those may include unsaturated FFA, lipid peroxidation products, and others, which may induce multiple inflammatory pathways, mitochondrial dysfunction, oxidative stress, and endoplasmic reticulum stress—all leading eventually to cellular damage and apoptosis.