Along with the rise in obesity has come the rise of issues affecting the liver.
The most prevalent condition worldwide is metabolic dysfunction-associated steatotic liver disease (MASLD), which replaces the term nonalcoholic fatty liver disease (NAFLD) to better reflect the underlying cause.
It’s estimated that close to 25 percent of all adults have MASLD. Of that group, 25 percent have the much more serious condition called metabolic dysfunction-associated steatohepatitis (MASH), which replaces the older term NASH, or nonalcoholic steatohepatitis (steato stands for fat and hepatitis, inflammation of the liver).
The overriding concern with MASH is that it puts you at risk for fibrosis, scar tissue that can worsen over time, sometimes to the point of cirrhosis. Cirrhosis used to be associated with alcoholism but can develop even if you never take a drink.
Here’s what you need to know to protect yourself. MASH starts with fatty liver, the result of “dysregulated metabolism” or insulin resistance—when your body doesn’t respond appropriately to the release of insulin, the hormone that helps convert the food you eat into energy.
Body fat is stored in cells called adipocytes. When you become insulin resistant, instead of containing the fat, adipocytes release it into your system in the form of fatty acids, which are immediately transported to the portal vein and into the liver. Looked at another way, having fatty liver is the earliest clue that that you have insulin resistance.
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Why doesn’t everyone with MASLD develop MASH? The liver has ways of dealing with this excess energy. It can convert and store the fatty acids as triglycerides, or its mitrochondria (the parts of cells that act as powerhouses) can burn the excess fat as energy, or the liver can repackage fat in the form of very low density lipoprotein or VLDL, and ship it out.
MASH develops when those fatty acids aren’t appropriately and completely dealt with. Their presence can lead to liver damage in the form of scar tissue, or fibrosis.
Risk factors
We don’t completely know why many people with a fatty liver are able to cope with it and why others go on to develop MASH, but we know that the greatest risks are having type 2 diabetes and being postmenopausal. Other risk factors include:
Being aware of MASH is the first step. Next is figuring out if you should have a conversation with your doctor to see if you have a fatty liver.
This is key for everyone with diabetes. Too often, when talking about the major consequences of diabetes—retinopathy (eye disease), neuropathy (nerve disease ) and nephropathy (kidney disease)—hepatopathy (liver disease) is left out of the conversation. Yet among people with diabetes, 70 percent have fatty liver, 35 percent have MASH and 17 percent have moderate to advanced fibrosis and likely don’t even know it.
Here are other risk factors that should prompt you to be evaluated:
A noninvasive imaging test called FibroScan and a blood test called ELF (enhanced liver fibrosis) can detect fibrosis in the liver and the level of scarring. Fibrosis is staged on a scale from F0 (no fibrosis) to F4 (cirrhosis). People whose fibrosis is F0 or F1 and who are obese and have diabetes face a greater threat from cardiovascular disease than liver disease.
Doctors target cardiovascular risk with GLP-1 drugs like semaglutide transpeptidase (Wegovy, Ozempic, and others). Apart from lowering blood sugar levels, these medications help to get rid of fat and inflammation in the liver. But they don’t help with fibrosis. Until recently, there was nothing to offer people who are F2 and higher, when it becomes important to focus on the liver.
In March 2024, there was a major breakthrough for people with MASH. The U.S. Food and Drug Administration approved resmetirom, the first-ever drug—a pill—to combat the condition. It was found to significantly decrease fatty liver by ramping up the liver’s mitochondrial function and improve or limit fibrosis for most participants. Biopsies done at the start of the trial and at week 52 found that 80 percent of participants experienced either fibrosis reversal or prevention of progression of their disease.
Just as with high blood pressure, diabetes and high cholesterol, MASH needs long-term management. In addition to medication, a patient-centered approach that tackles the root cause of the problem, obesity, is needed. This means exercise and a weight loss of 5 to 10 percent of body weight—the same lifestyle modifications suggested for a mild to moderate fatty liver, which include minimizing or excluding alcohol and cutting out fructose-containing beverages while drinking more coffee, which is absolutely good for liver health. These are important for liver health and longevity in general.
The goal when exercising is to increase your Vo2 Max—that’s maximum amount of oxygen that you could use during intense or maximal exercise. This measurement, which is done as a fitness test, is generally considered the best indicator of cardiovascular fitness and aerobic endurance. But that isn’t to say you need to work out at that level on a daily basis.
There are five heart rate zones when it comes to exercise, starting with Zone 1, which is used for warmup and recovery with a heart rate of 50 to 60 percent of your maximum [225 minus your age]. Successive zones go up by 10 percentage points to the top range of 90 to 100 percent in Zone 5 (which is not sustainable for long). The good news is that you don’t have to exercise all the way up to Zone 4. You can successfully build endurance capabilities in Zone 2, working for 30 minutes at 60 to 70 percent of your maximum heart rate.
An excellent goal is to aim for 10,000 steps a day, walking outdoors or on a treadmill. The importance of tracking steps was confirmed by a 2023 study review involving 220,000 people. It found that, while 4,000 steps a day decreases your risk of dying from any cause, for every additional 1,000 steps you take a day beyond this, you can lower all-cause mortality by 15 percent. For older adults, taking between 6,000 and 10,000 steps a day reduced it by 42 percent.
When you walk those steps, do it with the idea that you’re building heart health and increasing longevity, but not with the idea of losing weight. You can’t out-exercise the fork.
To lose weight, you need to make new mitochondria, the fat-burning cells mentioned above. And the best way to do that is intermittent fasting. Here’s why: There are roughly 1,500 calories of glycogen stored in your liver, and you have to deplete that before you can really start to deplete fat in your body. Most people don’t work out beyond 1,500 calories a day: That would take two hours of solid running.
What typically happens is people work out for 30, 45 or, for a few, 60 minutes, burning 300, 400, or 500 calories. With the next meal, they just replace the used glycogen. That’s why they don’t ever lose weight. The way to get around that is to fast if you’re able.
Whether it’s intermittent fasting, such as the well-known 16/8 (with eating confined to an eight-hour block each day) or limiting calories to 500 on two days per week, the longer you fast, the more time you spend in a glycogen-depleted state, burning fat. Always talk to your doctor first, but there is evidence that this is safe and effective if you have diabetes.
Dr. Harrison is the force behind the website HepVita.com dedicated to educating people about MASLD and MASH. Features include two online tools to help you assess your liver health. The “Simple Liver Health Meter” calculates your risk of liver disease based on your answers to simple questions about your health status and helps determine if you should be evaluated for fatty liver. The “FIB-4 Meter” calculates whether you’re at risk of liver scarring based on your age and three numbers that are included on routine blood tests: your platelet count and AST and ALT liver enzyme levels. If your risks are in the danger zone, schedule an appointment to talk to your doctor.
