Battle of the Abbreviations: NAFLD, NASH, Cirrhosis (not an abbreviation)
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Fats are tasty in food, but not particularly good in the bloodstream. They can also be toxic to the liver and to cells in general. We have special cells called adipose cells that store fat in our body. These cells have defenses against dangerous fat components called free fatty acids. Free fatty acids are the high-energy parts of fats, the part that gives you energy. Fatty acids are a great way to store energy and can be turned into power for your body, but the high energy content can also be dangerous in the wrong places.
The liver transforms free fatty acids into usable energy. From here, the energy is delivered to cells all over the body. The liver is part of the system that makes sure the body’s energy demands match the available energy. Unfortunately, when too many free fatty acids are delivered to the liver, they can start to build up in the liver tissue and cause damage.
Fatty liver is one of the most common ailments in Western countries. One in every three to four people in the US have a fatty liver. Excessive alcohol consumption can cause a fatty liver, but most sufferers develop non-alcoholic fatty liver disease (NAFLD). Either way, people have steatosis. Steato- means fat, and -osis indicates a condition, especially an abnormal one. Steatosis of 5-10% is problematic and is the earliest indication that the liver is starting to suffer damage. Many people with fatty liver and no other abnormalities can make a full recovery, usually by stopping whatever is causing the steatosis.
We know that alcohol can directly damage the liver, but how does NAFLD start? There are multiple possible causes, but some similarities exist. Excess fat released from fat cells, excess fat created by the liver, and excess fats from the diet all find their way into the liver. These are normally not an issue, but all are affected when the body isn’t regulating insulin properly. Insulin lets body parts know when you have food or are starving. When insulin isn’t processed correctly the body thinks it’s starving and tries to compensate - even when there is plenty of food present. In the middle of this, the liver suffers.
After a prolonged period of fat accumulation, a patient with NAFLD may develop non-alcoholic steatohepatitis, or NASH. Steato- for fat, hepat- indicating the liver, and -itis which means inflammation. Steatohepatitis is an inflamed, fatty liver. This second leg of the terrible journey develops when fat causes inflammation in the liver. The gut changes and gives the wrong signals to the liver. Cells develop insulin resistance and can’t convert sugars into energy or fats correctly. Free fatty acids cause cell problems and elicit an immune response. Stresses on the liver cause a feedback loop, where inflammation disrupts cell function. The body tries to fix the liver, but can’t overcome the massive amount of dangerous fats. Cells in the liver die and the living cells can be damaged trying to compensate. With NASH, the inflammation is long-lasting, also called chronic.
The liver can regenerate from NAFLD and NASH. It can’t sustain forever, however. When the liver is permanently damaged the tissue can scar and die. This is a permanent reduction in liver function. We call this scarring Cirrhosis. Cirros- is the Greek word for yellow-brown (the color of a dying liver), and -osis refers to a condition, especially an abnormal one. Cirrhosis has multiple stages, and can be asymptomatic, but cannot be recovered from without intervention. The current treatment for cirrhosis is a liver transplant.
Though we’ve been talking about the dangers of fats in the bloodstream and liver, it should be noted that the body makes a lot of these fats out of carbohydrates - sugars. A healthy diet without too many sugars and with lots of exercise are the best preventative measures for these conditions. Conditions related to insulin resistance, such as type 2 diabetes and metabolic syndrome can both cause and be caused by these conditions. Also, even though we have presented these as a pathway, note that you can progress back from NASH to NAFLD or even become symptom-free, it’s not a one-way journey! If you have any of these conditions, talk to your primary care physician to look for solutions. Also, keep an eye out for clinical research trials that may alleviate symptoms or the underlying fat buildup.
References:
Pierantonelli, I., & Svegliati-Baroni, G. (2019). Nonalcoholic fatty liver disease: basic pathogenetic mechanisms in the progression from NAFLD to NASH. Transplantation, 103(1), e1-e13. . https://doi.org/10.1097/TP.0000000000002480
Sanyal, A. J. (2019). Past, present and future perspectives in nonalcoholic fatty liver disease. Nature reviews Gastroenterology & hepatology, 16(6), 377-386.
