MASH, MASLD, and your body: Understanding the long-term impact

Last updated Sept. 3, 2024, by Lindsey Shapiro, PhD
Fact-checked by Patrícia Silva, PhD

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its more serious form metabolic-associated steatohepatitis (MASH) are types of fatty liver disease. They both involve higher than usual amounts of fat accumulating in the liver. It can affect not only the liver, but also the rest of the body, especially if left untreated.

Prior to an update in 2023, MASLD was referred to as nonalcoholic fatty liver disease (NAFLD). MASH, where liver fat leads to inflammation and scarring, was previously called nonalcoholic steatohepatitis (NASH).

MASLD refers to a fatty liver that develops associated with any of five cardiometabolic risk factors: being overweight or obese, or having high blood sugar or type 2 diabetes, high blood pressure, or elevated fats in the blood (triglycerides or cholesterol).

Over time, it is possible for MASLD/MASH to cause irreversible liver damage and dysfunction.

People with these diseases are also at an elevated risk for a range of other health issues, including cardiovascular disease and kidney problems. It is possible, with lifestyle interventions and sometimes medications, to reverse the disease before it becomes more serious.

How MASLD and MASH affect the liver

Fatty liver disease, now referred to as steatotic liver disease, generally refers to excess fat built up in the liver. Although the exact ways MASLD and MASH develop are not completely understood, metabolic factors are believed to drive increased fat production in liver cells and affect the organ’s ability to clear out the fat.

The liver serves many important functions in the body, including removing toxins from the bloodstream, and aiding digestion and metabolism. At its most severe, MASLD/MASH can lead to irreversible damage that prevents the liver from doing these functions.

There are generally four stages of fatty liver disease progression. How significantly the liver is affected depends on what stage it is.

Steatosis

In this early stage of disease, abnormal fat deposits are seen in the liver, but they have not yet caused any significant problems. Usually, there aren’t any obvious MASLD symptoms at this stage, and many people don’t know they have a problem until it is detected in medical tests.

Often the liver will stay in this disease stage and not progress to more serious problems. Up to a quarter of adults in the U.S. have MASLD, but only around 20% of them will develop MASH, which is the next stage of fatty liver.

Steatohepatitis

Eventually, fat buildup can lead to liver inflammation (hepatitis) that begins to cause damage to the liver. This stage marks the transition from MASLD to MASH. Liver inflammation at this point can lead to symptoms such as pain in the upper right abdomen (where the liver is located), fatigue, and appetite loss, but many people still may not notice any symptoms.

Fibrosis

While the liver is working hard to heal itself from disease-related damage, it progressively generates scar tissue in a process called fibrosis.

Depending on the amount of scarring, the liver may not be functioning properly. Scar tissue may start to reduce blood flow through the liver, interfering with it receiving oxygen and nutrients. Reaching this stage can take several years.

Even with fibrosis, you may not have symptoms of MASLD/MASH, but may experience persistent abdominal pain, fatigue, or appetite and weight changes.

Cirrhosis

When fibrosis becomes widespread and permanent and substantially impairs the liver, it becomes cirrhosis. This is when you are most likely to experience symptoms, which may include:

nausea and vomiting
yellowing of the skin and eyes (jaundice)
severe itch (pruritus)
painful abdominal swelling due to fluid buildup (ascites)
easy bruising or bleeding
visible spider-like blood vessels
loss of appetite or weight loss
swelling in the legs, feet, or ankles.

Even with cirrhosis, the liver may still be able to do its most critical functions, keeping symptoms at bay for some time.

Eventually, however, your liver may reach a stage called decompensated cirrhosis, where it can no longer function adequately and is approaching complete liver failure. At this point, a liver transplant is usually necessary for survival.

People with cirrhosis are also at an increased risk of liver cancer, particularly a type called hepatocellular carcinoma. Around 90% of people who have hepatocellular carcinoma also have cirrhosis.

How MASLD and MASH affect the rest of the body

While MASLD/MASH is a liver disease, it also can cause many non-liver-related issues. It is believed that because the liver is such a critical organ that when it’s unable to take care of its usual functions, it can have a widespread impact on the body. It may also be that the metabolic conditions underlying MASLD/MASH cause problems with other organs.

Cardiovascular disease

Cardiovascular disease is common among people with MASLD. In fact, cardiovascular disease, not liver failure, is the leading cause of death in people with MASLD. Those who develop MASH and advanced fibrosis or who also have diabetes may be at a higher risk of cardiovascular issues.

The relationship between cardiovascular disease and MASLD is likely linked to the two diseases having a number of metabolic risk factors in common, such as obesity, high blood pressure, diabetes, and high cholesterol. However, some evidence suggests MASLD itself leads to an additional risk of early cardiovascular disease.

Types of cardiovascular issues seen in MASLD include:

high blood pressure
coronary artery disease, where plaque builds up in the blood vessels of the heart and makes blood flow more difficult
angina, a chest pain or discomfort that arises when the heart muscle doesn’t receive enough oxygen-rich blood
arrhythmia (abnormal heart rhythm)
heart failure
problems with the heart’s valves
ischemic stroke, where blood flow to the brain is blocked.

Kidney disease

People with MASLD also experience chronic kidney disease at a higher rate than what’s seen in the general population. It seems to be higher once you have progressed to MASH and advanced fibrosis.

While shared metabolic risk factors may play a role, emerging evidence suggests MASLD itself may cause kidney damage independently of these factors, by way of several different mechanisms.

Some of the symptoms of kidney problems can overlap with those caused by cirrhosis. Signs of kidney issues include:

tiredness and fatigue
dry and itchy skin
urine changes, including frequent or infrequent urination, blood in the urine, or foamy urine
swelling
poor appetite
muscle cramping.

As with liver disease, if chronic kidney disease causes the kidneys to no longer do their usual function, it will lead to kidney failure and dialysis, or a kidney transplant will be needed for survival.

Hormonal conditions

The liver interacts with the body’s endocrine system — the network of glands that produce hormones — in complex ways. For this reason, MASLD can be accompanied by a number of different hormonal irregularities including:

type 2 diabetes, where blood sugar levels get too high because the body does not respond properly to the hormone insulin, which removes sugar from the blood
polycystic ovarian syndrome, where excess male sex hormones (androgens) are linked to menstrual irregularities in females of reproductive age and cysts develop on the ovaries
hypothyroidism, where the thyroid gland, which produces hormones that regulate metabolism, is underactive.

Cancer

People with MASLD also may be at an increased risk of developing other cancers. A 2022 study reported MASLD is associated with a 1.5 to 2 times higher risk of developing cancers not of the liver, especially gastrointestinal cancers such as of the esophagus, stomach, pancreas, or colon.

Other types of cancer for which MASLD patients may be at an increased risk include gynecological or urinary system cancers, breast, and lung cancer. Additionally, fatty livers may be a target for cancers in other organs that eventually spread to the liver.

Is MASLD reversible?

The liver is very resilient and able to naturally heal itself from damage and injury up to a certain point, but the underlying liver disease will always be working against the organ’s efforts to recover. This is why reaching a prompt MASLD/MASH diagnosis and starting to manage the condition before it gets worse is the best way to reverse the disease.

MASLD treatment mainly involves making lifestyle changes and trying self-care strategies to address the underlying metabolic MASLD causes.

In the earliest stages, these changes can completely clear fat deposits from the liver and reverse the disease.

Ways to help reverse MASLD include:

eating a healthy diet
avoiding smoking and excessive use of alcohol or other substances that could harm the liver
regular exercise
losing weight
managing stress and staying well rested
taking medications recommended by your doctor for managing MASLD and related conditions.

The more scar tissue that builds up, the harder it becomes for the liver to repair itself. Still, more intensive lifestyle changes can help at least partially reverse or stop the progression of the disease. Disease-specific medications are limited.

Making lifestyle changes is also critical for counteracting the effects of metabolic dysfunction throughout the rest of the body.

Even if the liver heals itself, you may still be at risk for other issues, such as heart disease or kidney problems, if underlying factors such as obesity or high blood pressure are not addressed. Organs including the heart and kidneys don’t have the same regenerative capacity as the liver, so it is especially important to protect them.

Overall, continuing to live a healthy lifestyle in the long term can help prevent MASLD from returning and improve your overall general health.

It is important to work with your healthcare team to come up with a management plan that best addresses your specific needs and gives you the best possible chance of reversing or stopping the progression of MASLD/MASH.

Liver Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.