Nonalcoholic Fatty Liver Disease (NAFLD)
Non-alcoholic fatty liver disease (NAFLD) is a condition in which excessive fat (more than 5% of liver weight) accumulates in the liver due to causes unrelated to alcohol.
Nonalcoholic fatty liver disease (NAFLD) refers to a spectrum of liver diseases characterized by an excessive accumulation of fat in the liver without excessive alcohol consumption (i.e., > 21 standard drinks per week for men and > 14 standard drinks per week for women). It can be broadly divided into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). NAFL is less severe and only includes excessive liver fat (i.e., the presence of fat in > 5% of liver cells), whereas NASH includes excessive liver fat plus liver inflammation and damage.
Most people with NAFLD do not present with symptoms, and the disease remains silent until it has progressed to an advanced stage. In the early stages, fatigue and upper abdominal pain may be reported. Elevated levels of serum alanine aminotransferase and aspartate aminotransferase are also typically observed. In cases of very severe NAFLD, jaundice (i.e., yellowing of the eyes and skin), edema, ascites (i.e., excess fluid trapped in the abdomen), and/or confusion may be present.
Liver biopsy is considered the gold standard for diagnosing NAFLD and is essential for diagnosing NASH, as it is the only procedure that can reliably differentiate it from NAFL. Imaging methods, such as ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), are more commonly used, but their ability to detect mild NAFL is poor. MRI seems to be the precise imaging method.
There are no Food and Drug Administration-approved medications for treating NAFLD. Current guidelines suggest that pharmacological treatment should be reserved for people with biopsy-proven NASH. Off-label medications are mainly used for treating risk factors (i.e., obesity, insulin resistance, hypertension, dyslipidemia) with the aim of preventing disease progression.
Lifestyle modification with the aim of inducing weight loss is the cornerstone of NAFLD treatment. A weight loss of at least 5% of initial body weight is effective for reducing liver fat, and a weight loss of 7–10% can improve features of NASH. In this respect, the macronutrient composition of the diet is much less important than the energy content; an array of dietary patterns can be effective as long as they facilitate sustained weight loss.
NAFLD reflects an imbalance of energy metabolism in the liver: more energy enters the liver than it can dispose of, resulting in a net accumulation of energy as triglycerides. Overnutrition and sedentary behavior primarily lead to the development of NAFLD, but there are a variety of other factors that further influence the development and progression of the disease, including genetics, aging, fat tissue dysfunction, gut dysbiosis, and insulin resistance.