Non-alcoholic fatty liver disease

Definitions & Key takeaways

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.

Chapters:

Watch video only

Introduction0:00–0:57

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, unrelated to alcohol or viral causes. Typically, it affects individuals with metabolic syndrome, which includes a combination of three of the following five diagnosis: 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.

Pathology0:57–2:01

Although the precise mechanism of nonalcoholic fatty liver disease is not 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 pushing 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, shows widespread steatosis which makes the liver appear large, soft, yellow, and greasy.

Complications2:01–3:45

Over time, the 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 particularly vulnerable to initiators such as the reactive oxygen species like the hydroxy 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. The fatty acid radical is unstable and will react with non-radicals, including molecular oxygen and undamaged fatty acids.
This goes on until one radical species reacts with another radical species terminating the reaction. This process damages lipid membranes leading to things like mitochondrial dysfunction and eventually cell death.
Cell death generates inflammation, and together the process of steatosis and inflammation is referred to as steatohepatitis.
In the absence of alcohol this is called nonalcoholic steatohepatitis or NASH. In addition to bloated and dying hepatocytes, there may be additional histopathologic changes like the presence of Mallory-Denk bodies which are tangles of intermediate filaments that can be seen in the cytoplasm of hepatocytes.
The mechanism for how these form remains unclear. Hepatocyte damage also attracts neutrophils into the liver tissues.
Finally, chronic steatohepatitis can cause liver stellate cells to lay down fibrotic tissue causing the disease to be classified as fibrosis.
As the process of fibrosis continues, the overall architecture of the liver changes, to the point where the disease is classified as cirrhosis.

Symptoms3:45–4:48

Even at the advanced stage of steatohepatitis, an individual might have no symptoms. And when there are symptoms, they are often vague - like fatigue or malaise.
Once there is significant liver damage, there can be hepatomegaly or enlargement of the liver, pain in the right upper quadrant of the abdomen, jaundice, and even an accumulation of fluid in the peritoneal cavity called ascites.
Because hepatocytes are being destroyed, there can be an increase in liver enzymes such as aspartate transaminase (AST) and alanine transaminase (ALT).
Classically, progression of steatosis to steatohepatitis and then to cirrhosis causes an increase in the ALT and sometimes AST.
In contrast, alcoholic liver injury generally causes the a big increase in AST and a more modest increase in ALT giving a AST:ALT ratio generally > 2.
If nonalcoholic fatty liver disease is suspected, a diagnosis can be made with imaging studies such as ultrasound, a CT scan, or an MRI to look for fatty infiltrates.

Diagnosis4:48–5:13

In addition, a biopsy of the liver can be done to confirm the diagnosis and assess the severity of the disease. Generally speaking, a liver with more than 5% fat content is considered abnormal.

Treatment5:13–5:39

Steatosis and to a lesser degree steatohepatitis is generally reversible by addressing the underlying cause, however, that’s generally not the case once fibrosis and cirrhosis have set in.
The goal is to reverse the factors that contribute to insulin resistance, primarily through a healthy diet and an active lifestyle, as well as medications to control blood glucose levels if needed.

Review5:39–6:21

OK, quick recap: nonalcoholic fatty liver disease occurs when fat is deposited in the liver - a process called steatosis.
Inflammation from steatosis can lead to steatohepatitis, and chronic steatohepatitis can lead to fibrosis, and ultimately to cirrhosis.
This spectrum of disease is thought to be caused by insulin resistance, and depending on the stage of disease, it can be reversed with careful attention to diet and exercise - as well as medications to help control blood glucose levels.
Thanks for watching, you can help support us by donating on patreon, or subscribing to our channel, or telling your friends about us on social media.