ABIM Exam Disease of the Week Profile: Non-Alcoholic Fatty Liver Disease

“Could you please double size my cheeseburger, give me some extra-large fries, two cherry pies, and a large soda?” It is this type of diminished willpower and generous demands that lead to unattractive, expanded waistlines and the ever so popular “love handles” to develop. Obesity increases the risk of developing certain medical conditions like dyslipidemia, coronary artery disease, diabetes mellitus, obstructive sleep apnea, and stroke. These are just some of the few common medical conditions that can result from obesity. The ABIM Board Exam disease condition that I will discuss today as the disease of the week is non-alcoholic fatty liver disease (NAFLD). It represents the third most common cause of abnormal transaminases after medications and alcohol.




NAFLD is just what the name applies: fat accumulation in the liver that is not due to alcohol use. It is increasingly being recognized as the most common cause of liver disease in the United States. The reason behind this phenomenon is simple: people in the United States have an infatuation with fast food that is leading to higher rates of obesity. Obesity and insulin resistance play the strongest role in the disease process. Approximately sixty percent of obese individuals will develop fatty liver disease or NAFLD. NAFLD (without inflammation) is more common in women than men. If inflammation is present, the diagnosis steatohepatitis is given.


The main pathophysiology in the development of NAFLD can best be understood by the “two hit phenomenon.” Initially, there will be accumulation of fat in the liver because of years of eating unhealthy, greasy, high fat content food. The second “hit” involves beta oxidation and lipid peroxidation of fatty acids that leads to reactive oxidative species and mitochondrial injury. The mitochondria (powerhouse of the cell) is where adenosine triphosphate (ATP) is generated. ATP is used to supply cellular energy. Therefore, the mitochondria has an important role in regulating cell growth, cell differentiation, cell signaling, and eventually apoptosis (cellular death) of cells that are not properly functioning. With mitochondrial injury occurring because of production of reactive oxidative species, cirrhosis can develop because of fat accumulation.


Indian males have a higher predisposition for the development of NAFLD because of genetic mutations in the single- nucleotide polymorphisms (SNPs) T455C and C482T of APOC3. Polymorphism means genetic variation. APOC3 is a protein that inhibits lipoprotein lipase and hepatic lipase, which will inhibit the uptake of triglyceride-rich particles. With higher genetic variability, APOC3 levels are increased and, therefore, lead to hypertriglyceridemia because of decreased triglyceride uptake into the cell.




It is important to understand the risk factors of NAFLD for general practice and for your Internal Medicine Board Review.


Some of the most common risk factors or causes of NAFLD are: obesity (BMI usually greater than 30), insulin resistance (type 2 DM), long term use of corticosteroids, amiodarone use, dyslipidemia, protein malnutrition, prolonged IV, and hyperalimentation.




With alcoholic liver disease, AST elevation tends to be higher than ALT levels, usually in a ratio of 2:1. The transaminase levels in alcoholic hepatitis will rarely reach 500 IU/L. NAFLD, on the other hand, usually displays ALT elevation more than AST with characteristic risk factors described above. The most common scenario of suspecting an individual to have NAFLD is a patient who has slightly elevated ALT levels and a high body mass index. Normal LFTs however do not exclude NAFLD. When your clinical suspicion is high for NAFLD, a right upper quadrant ultrasound should be obtained to confirm the presence of steatosis (fat accumulation). Definitive diagnosis of NAFLD, however, is by performing a liver biopsy. The biopsy can determine the severity of inflammation and degree of fibrosis to predict if patients are at risk of developing cirrhosis in the future.




Although there is no standardized treatment for NAFLD, the best advice for patients to improve liver function tests is to reduce weight, control diabetes mellitus (if present), and control cholesterol. Participating in an exercise regimen can help individuals to gradually lose weight and prevent the progression of cirrhosis to occur. Interestingly, rapid weight loss may actually increase inflammation and fibrosis. Along with the above measures in managing NAFLD, metformin, statins, and the thiazolidinediones have shown promising results in controlling NAFLD.


In conclusion, maintaining a healthy weight and exercising regularly can prevent the onset of NAFLD. With cardiovascular exercise and weight resistance training, individuals get more blood flow to the brain that creates a natural “high” for individuals and improves mental functional capability. With this improved mental function capability, why not use that to your advantage and create the mental toughness or will-power to indulge in a well-balanced diet instead of eating foods that will decrease your quality of life and increase your chance of developing conditions like NAFLD?


You can see all the previous ABIM Exam disease of the week blog posts at the Knowmedge Blog. You can find also additional topics and questions directly from the Knowmedge Internal Medicine ABIM Board Exam Review Questions QVault.

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