Introducing Metabolic Dysfunction ASsociated Liver Disease (MASLD) - a story about the rebranding of Non-Alcoholic Fatty Liver Disease
For several years, decades even, the medical condition that results from fatty infiltration into liver cells and the toxic environment that ensues risking liver cirrhosis has been referred to as Non-Alcoholic Fatty Liver Disease (NAFLD). But in the past couple of years, the medical field has been pushing to change the name, rebrand it, if you will. I support this rebranding to MASLD and will explain why the first name existed and why this rebranding effort is a much more appropriate designation for the disease.
Why was it called NAFLD in the first place?
Liver cirrhosis is a very serious medical condition where the liver gets so scarred over from fibrosis that it is no longer able to perform its very crucial functions, such as energy storage, hormone production, and detoxification of cellular breakdown products, to highlight just a few of its very many important functions in our body. There are many causes of cirrhosis, one of the main ones being chronic alcohol use and abuse. However, NAFLD distinguished itself from alcohol related disease under the microscope. Looking at the cells, clusters of liver cells are seen ‘ballooning’ with fat infiltrates. Whenever fat deposits itself into areas it should not be, an inflammatory response develops and eventually leads to fibrous bands forming and liver cell death. If this continues unchecked, cirrhosis develops. Liver disease from alcohol does not look like this under the microscope. So, it was given its name by describing the result of fat invading liver cells, not due to alcohol.
BUT… the natural question is WHY does this fat invasion into liver cells even start in the first place?
The major, if not, main culprit: insulin resistance. When cells are unable to respond to the body’s own insulin in the way that it should, the pancreas will increase insulin production - this is called hyperinsulinemia. From a lifestyle perspective, and especially honing in on dietary patterns, the Standard American Diet, which is exceedingly high in BOTH saturated fat and refined carbohydrates, is especially poised at leading individuals toward the development of insulin resistance. Now, no one meal in one dose will cause disease. However, a pattern of eating, more days out of the week than not, of high saturated fat or added fat foods and high refined carbohydrate or added sugars will lead to insulin resistance.
In the state of high insulin and higher blood sugars and fat stores in the body that have reached capacity, these two forms of excess energy either get converted to or stored as fat in alternate fat storage sites that, in all honesty, were never meant to store fat. One of these favorite alternate sites - the liver.
So the fat storage in the liver is a result of hyperinsulinemia caused by insulin resistance, which is a metabolic dysfunction. THEREFORE, the name metabolic dysfunction associated liver disease now reflects the cause of the disease. While this may seem trivial, I find this to be so incredibly important and something that can have a big impact on how we approach the management, and key to decreasing how common it is. Because calling it by its cause, we can now focus on addressing the cause - at its core.
There are 3 Stages of MASLD:
Stage 1 - MASLD, which 1 out of every 4 adults in the U.S. has
Stage 2 - MASH, or metabolic steatohepatitis where now many inflammatory cells have invaded the liver because of the fat deposits that are not supposed to be there, which 25% of individuals with MASLD will go on to develop
Stage 3 - Cirrhosis of the liver, where the inflammatory cells lead to significant scarring and damage, which 25% of individuals with MASH will go on to develop.
This is a big problem, especially considering that since 2014, it is now rivaling alcoholic cirrhosis as the leading cause of liver transplantation. Yes, you read that right. MASLD is now becoming the number one reason for liver transplantation (JAMA 2020 3(2)). That is frightening, especially considering how prevalent this medical condition is and how little time is spent discussing it during clinical visits.
Not only is it a threat unto itself (liver damage), but individuals with MASLD are also at a much higher risk of developing type 2 diabetes, heart disease, and kidney disease. This is not surprising, considering that all of these other medical conditions also have insulin resistance as a major cause of the disease.
How is it diagnosed?
Blood Tests
Specifically, looking at ALT and AST elevation. Frequently, the ALT is higher than the AST. This can give a clue as to the possibility of existing MASLD. This should be worked up further if found on blood tests.
Imaging
Liver ultrasound +/- elastography, which is a way to look at liver stiffness
So, what can be done to treat it?
Well, we always, always start with lifestyle optimization. Since lifestyle habits fuel insulin resistance, it is important to understand how to adjust certain lifestyle habits to decrease and reverse insulin resistance.
Here are some quick lifestyle tips to reverse insulin resistance.
Nutrition:
Fill your food options with vegetables, beans, lentils, nuts, whole grains, and fruit. Choose lean sources of protein and keep saturated fat to a minimum. Prioritize wholesome food over ultra-processed foods and avoid sugar-sweetened beverages and excess alcohol. Interestingly, 2 cups of black coffee a day has been shown in studies to have a positive benefit in MASLD.
Exercise:
Avoid spending the majority of your days being sedentary. Capitalize on ‘down-time’ during the day to do lunges, squats, walk around your room/house/office/building. Take stairs, do calf-raises. Make time to get in dedicated exercise.
Sleep:
I’ve written about sleep and its impact on insulin resistance in the past. Make sure to choose a bedtime and stick to it. Avoid technology screens 1 hour prior to bedtime and provide yourself a sleep opportunity of at least 8-9 hours. Even if you fall short an hour, you are still within that desired range.
Are there medicines for MASLD?
This is an area of very active, ongoing research. For years, nothing had been approved for specifically the use of MASLD. While medicines that improve insulin resistance, like metformin and GLP-1/GIP-GLP1 therapies, have been shown to improve certain properties of MASLD, they had not received FDA approval for the specific indication of treating NASH.
Just last month, however, the FDA approved the use of resmetirom, a once a day medicine that attaches to the liver-directed thyroid hormone receptor (THR)-β, designed to target key underlying causes of MASH - the more progressive form of MASLD. Even with the MASH category, the drug is indicated for those who have moderate to advanced fibrosis.
In summary - this disease which has been growing in prevalence and was previously called by the findings seen on a microscope, is now undergoing a rebranding, if you will. With this rebranding, it is shining light on the cause and by understanding the cause and treating it, we can really make significant impacts on reversing the course and sparing not only end-stage liver disease, but the risk of other metabolic dysfunction diseases
Article: Under NASH search in email https://www.medpagetoday.com/gastroenterology/generalhepatology/109187?xid=NL_breakingnewsalert_2024-03-14&eun=g851278d0r&utm_source=Sailthru&utm_medium=email&utm_campaign=RezdiffraAlert_031424&utm_term=NL_Daily_Breaking_News_Active