Non-alcoholic fatty liver disease

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Non-alcoholic fatty liver disease

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A 52-year-old man is brought to the emergency department after being found unconscious on the sidewalk. He is arousable to sternal rub. The patient’s family is contacted, and his next of kin reports that the patient is currently undomiciled. Past medical history is notable for hypertension. The patient has been drinking a pint of vodka daily for the last 12 years, but does not consume tobacco or illicit substances. Temperature is 37.0°C (98.6°F), pulse is 92/min, respirations are 13/min, and blood pressure is 156/95 mmHg. Physical examination reveals jaundice, palmar erythema, and pungent breath. The lungs are clear to auscultation. The abdomen is soft and mildly tender to palpation; there is shifting dullness to percussion. The liver is not palpable. Which of the following is most likely to be present if a biopsy of the patient’s liver is performed?

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Nonalcoholic fatty liver disease is actually a spectrum of disease, going from least to most severe—steatosis, steatohepatitis, fibrosis, and finally cirrhosis.

Nonalcoholic fatty liver disease results from fat deposition in the liver, which is unrelated to alcohol or viral causes.

Typically, it affects individuals with metabolic syndrome, which includes a combination of three of the following five diagnoses: obesity, hypertension, diabetes, hypertriglyceridemia, and hyperlipidemia.

Given how common metabolic syndrome has become, it’s not surprising that the rate of nonalcoholic fatty liver disease has also increased dramatically.

It’s a massive problem growing in lock-step with expanding waistlines, affecting about three quarters of all obese individuals, including many children.

Although the exact mechanism of nonalcoholic fatty liver disease isn’t clear, insulin resistance seems to play an important role.

Over time, insulin receptors on various tissues including the liver become less responsive to insulin, and as a result the liver goes into a mode where it increases fat storage and decreases fatty acid oxidation.

That means decreased secretion of lipids into the bloodstream, in the form of lipoproteins, and increased synthesis and uptake of free fatty acids from the blood, a process called steatosis.

Steatosis causes fat droplets to form within hepatocytes, some of which become large enough to cause the hepatocytes to swell up with fat and push the nuclei to the edge of the cell.

You can see this on a histopathology slide of the liver.

All of these white circles are large deposits of fat.

Zooming out and looking at the liver, you see widespread steatosis which makes the liver appear large, soft, yellow, and greasy.

Over time, that fat in the hepatocytes is vulnerable to degradation.

Unsaturated fatty acids, or fatty acids that have at least one double bond in their carbon chain, have hydrogen atoms that are especially vulnerable to initiators such as the reactive oxygen species like the hydroxyl radical that have an unpaired electron.

In this example the hydroxyl radical pairs with the vulnerable lipid hydrogen to make water and a fatty acid radical.

Summary

Non-alcoholic fatty liver disease (NAFLD) is a condition in which excess fat is deposited in the liver, leading to inflammation and scarring. NAFLD is a common liver disorder that affects people who do not drink alcohol excessively. NAFLD commonly affects people with metabolic syndrome, which includes a combination of three of the following five diagnoses: obesity, hypertension, diabetes, hypertriglyceridemia, and hyperlipidemia.

Symptoms of NAFLD may be subtle or absent in the early stages of the disease. In advanced stages, symptoms may include fatigue, abdominal pain, and jaundice. NAFLD can progress to a more serious condition called non-alcoholic steatohepatitis (NASH), which can lead to liver scarring and cirrhosis. Treatment for NAFLD may involve lifestyle changes such as weight loss, regular exercise, and a healthy diet to help reduce fat in the liver and improve insulin resistance.

Sources

  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
  4. "CURRENT Medical Diagnosis and Treatment 2020" McGraw Hill Professional (2019)
  5. "The Role of Intestinal Bacteria Overgrowth in Obesity-Related Nonalcoholic Fatty Liver Disease" Nutrients (2014)
  6. "Non-alcoholic fatty liver disease" BMJ (2014)
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