Non-alcoholic fatty liver disease (NAFLD) – causes, symptoms, diagnosis, treatment, pathology

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. 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. 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. 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. 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. 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. 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.


  1. We've updated this video! There was some issues with our AST and ALT numbers, so we've updated our phrasing: 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.

  2. idk if you take suggestions but I looked through your channel and couldn't find any videos on complex PTSD, could you make a video on it? I haven't found many good videos on it and I really think it should be more known.

  3. sir your videos are awesome……there are some channels they are stealing your videos ….keep watch on them….

  4. Ok,  Thank you for posting and corrections  .What can be done to stop the process on the reversible area  and not to progress to fibrosis?. When is the time for a biopsy ? Are NAFLD patients candidates for Statins as part of Metabolic syndrome treatment ?

  5. You should use the term 'dislipidemia' instead of hyperlipidemia. Because HDL levels not increased but decreased. Dislipidemia more accurate 🙂

  6. For the definition of the metabolic syndrome there needs to be hyperglycemia and not necessarily diabetes-prediabetes is sufficient for the criteria.

  7. Insulin inhibits b-oxidation and increases fatty acid, so the converse should take place in case of resistance, right?

  8. you are awesome. I review medicine with you after almost 20 years of my graduation. It was very helpful for a quick review.

  9. This is really awsome .. i nowadays started watching videos rather than books .. ur videos r simply superb… Keep it up ..!!

  10. We did a study to find the association between Nonalcoholic fatty liver disease (NAFLD) and incidence of diabetes mellitus. There we found that, subjects with ultrasonically diagnosed NAFLD have an increased risk of developing diabetes mellitus.

  11. take medication to control blood glucose? Just stop eating carbohydrates. You don't realize how sick you are with until you fix your diet.

  12. Osmosis your vedios are just awesome 😻 they are so helpful for cleaning pathology concepts! I have downloaded osmosis app though ! The thing i am encountering is a yellow lock 🔐 appearing on few vedios of each system!! Wanted to knw th reason and what could be done for it ! I also didn’t find any subscription option in that !!

  13. Please reply osmosis……i don't understand how insulin resistance cause storage of fat in liver and decreased fatty oxidation

  14. Instead of pumping yourself full of medications to "control" blood sugar levels, just stop eating foods high in sugar and low in fiber, then slowly start increasing your daily physical activity. It's really sad that people are so lazy and addicted to sugar they are killing themselves and think medications are going to make it all better, though that mindset is great for the pharmaceutical and sickcare industry bank accounts.

  15. Great vdos guys.. please do make a playlist on all chromosomes each individually???? .44 autosomes and 2sex chromosomes and their importance .

  16. What are your qualifications to speak on these topics? Please list your sources.
    I’m coming with good intent. I enjoy your videos. But want info on your credentials

  17. So what the heck is a "healthy diet" and why didn't you tell us this most important information? It seems like it is impossible to know anymore!

  18. Hey Osmosis, love the vids. Correction to metabolic syndrome criteria, I believe you look for low HDL, and not hyperlipidemia. Unless I'm confusing something. Let me know.

  19. oh my god the meow of the cat in 5:31 scared me i thought it was my cat that wanted something.
    Also this video is awesome, keep it up!!

  20. I'm watching this at 1 am and I just lost it with the fat guy running to catch a tomato 😂.
    Thank you for the video and for making me laugh so much!

  21. Whenever i look for any videos about the complicated topics in medical science ,, first of all, i Search in your channel.. This is a very good And initiative channel for medical students..
    . keep it up.. Make more videos on medicine complicated topics.. Thank you brother.

  22. BEST MOST INFORMATIVE VIDEO I HAVE SEEN YET… & I think I am in Big Trouble… I Don't Drink.. I thought I was taking good care of my liver. I had Carcinoid Cancer. They say it is gone. But Dr had me on 14 meds. & Gabapenton was one of those. Made me Crave Sweets. & Not ear Right. Others cause liver damage. So why aren't we being made more informed about this… ! Great Video. Wish that Sorry Dr had EXPLODED THIS…!!!

  23. didn't get why insulin decreases fatty acids oxidation ! isn't supposed to increase it since TAG is the main source of Energy when insulin resistance appear ?

  24. I found a program consisting of a completely natural way to treat fatty liver from the comfort of one's home. do you want to know?

  25. You're absolutely right. However, I do not understand the biological difference between alcoholic and non-alcoholic fatty liver? How do I know which one we have? Because today almost everyone drinks alcohol and many of them a lot. …. ??? Thx.

  26. My younger brother started feeling stomach ache and he started feeling swollen in the stomach. There was no relief even after taking many medicines. Then we took him to Dr. Vikram Chauhan and Dr. Sir after examining Told him that he has fatty liver disease. Dr. Sir gave my brother to take liver care pack. My brother got cured with the use of 2 months of that Ayurvedic pack.

Leave a Reply

(*) Required, Your email will not be published