Patatin-like phospholipase domain-containing protein 3 (PNPLA3) also known as adiponutrin is a protein that mediates the break down of fat and can increase hepatic fat levels based on its expression. Their genetic variation can explain this. People of African American origins have lower rates of NAFLD compared to Hispanic Americans despite having higher rates of obesity and diabetes.
Both nutritional overload states such as total parenteral nutrition and malnutrition (as in Kwashiorkor and celiac disease) are associated with NAFLD. Other metabolic and genetic conditions that are associated with NAFLD are polycystic ovary disease, lipodystrophies, mitochondrial diseases, Weber-Christian disease and Wilson disease. About three-quarter of patients with insulin resistance and type 2 diabetes mellitus have fatty liver disease with a higher prevalence of cirrhosis. Metabolic syndrome (which comprises of obesity, type 2 diabetes mellitus or hyperinsulinemia, hypertension, and dyslipidemia) is strongly associated with NAFLD. Obesity has a strong association with NAFLD. Ĭertain conditions have been associated with NAFLD and NASH. NASH is not a diagnosis of exclusion and can be associated with other liver conditions such as chronic hepatitis C. NASH is classified into two types, primary which is related to obesity and diabetes in the absence of excessive alcohol intake, and secondary which is toxin or drug induced. NASH can progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma with about 30% to 40% of patients developing fibrosis. These cutoff values are not accurately defined, especially in patients with prior history of heavy alcohol use and those who are prone to NASH.
The acceptable level of daily alcohol consumption is considered to be less than 20 g/day in men and 10 g/day in women. The diagnosis of NAFLD should not be made in a patient who has a history of significant alcohol consumption. NAFLD includes both nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) which is diagnosed when there is evidence of inflammatory activity and hepatocyte injury in a steatotic liver tissue.
Although, minor deposition of fat can occur in the liver of healthy adults, deposition of fat in at least 5% of hepatocytes is considered pathologic. Nonalcoholic, fatty liver disease (NAFLD) is defined as the ectopic accumulation of fat in the liver (hepatic steatosis) when no other causes of secondary liver fat accumulation are present.
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