MASH and fibrosis: Understanding the connection

Last updated Jan. 24, 2025, by Marisa Wexler, MS
Fact-checked by Patrícia Silva, PhD

Metabolic dysfunction-associated steatohepatitis (MASH) is a form of chronic liver disease involving excessive buildup of fat in the liver that leads to inflammation and liver fibrosis (tissue scarring). MASH and fibrosis are intricately linked, and understanding the connection between the two is key for managing the disease and liver health.

How MASH affects the body

MASH is a severe manifestation of metabolic dysfunction-associated steatotic liver disease (MASLD).

MASLD is a type of fatty liver disease marked by an excessive buildup of fat in the liver in people who have other underlying metabolic issues, including obesity, high blood pressure, diabetes, high blood fat levels, and/or high blood cholesterol levels.

MASLD and MASH were previously known as nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), respectively, but the nomenclature was updated in 2023 to increase accuracy.

MASLD is characterized by excessive amounts of fat in the liver, leading to abnormal fat deposits referred to as steatosis. When MASLD progresses to MASH, it means that the buildup of fat is driving inflammation (steatohepatitis) and liver scarring (fibrosis), which can cause damage to liver tissue and interfere with normal liver function. In the most extreme cases, it can lead to cirrhosis, which refers to widespread scarring of the liver causing substantial issues with liver function.

In addition to affecting the liver, MASLD and MASH also can cause problems in other parts of the body, such as cardiovascular disease, kidney disease, and hormone abnormalities, as well as increasing the risk of some cancers.

MASH can develop in anyone who has MASLD. The causes of MASH and the reasons why MASLD progresses into MASH aren’t fully understood, but MASH is especially common in people who have metabolic syndrome, which refers to several metabolic issues occurring at the same time. This is why there is a close connection between metabolic syndrome and liver disease. Risk factors for metabolic syndrome — namely insulin resistance, a sedentary lifestyle, genetics, and the use of certain medications — can also be MASH risk factors.

MASH and fibrosis

In all body tissues, cells are held together by a network of proteins and other molecules known as the extracellular matrix (ECM). The ECM gives structure to the body’s tissues and provides important molecular signals to regulate cell function.

At the molecular level, scarring means more ECM is being produced. Normally, this plays an important role in inflammation and wound healing; when a tissue in the body is damaged, inflammation is triggered to repel infectious invaders and promote repair of the damaged tissue.

But in MASH, the normally beneficial system goes awry as the buildup of fat in the liver causes inflammation to spiral out of control. MASH is marked by persistent inflammation, which means there are constant signals being sent to deposit ECM and make new scar tissue. Because the inflammation is continuous, these signals never stop, so more and more scar tissue is made.

Ultimately, this leads to fibrosis, which is when an excessive buildup of ECM causes liver tissue to become abnormally stiff, blocks blood flow, and interferes with normal signaling between liver cells. It becomes a vicious cycle as fibrosis causes tissue damage in the liver, which in turn causes more inflammation, and, consequently, further scarring that spreads throughout the liver. Over time, scarred tissue in the liver replaces healthy tissue.

Liver fibrosis is commonly divided into stages based on the extent of the scarring. There are five stages of liver fibrosis, ranging from F0 (no fibrosis) to F4 (cirrhosis).

When fibrosis is detected in the earliest stages, it may be possible to reverse the scarring if the underlying cause of inflammation can be addressed. But once fibrosis advances the scarring is usually irreversible. For this reason, an early diagnosis is vital for allowing the best outcomes, so testing for liver fibrosis is usually a key part of MASH diagnosis.

Liver fibrosis may be diagnosed via a biopsy, a test where a small piece of liver tissue is removed and taken to a lab for analysis, or via imaging tests that examine the stiffness of the liver to detect evidence of excessive scar tissue. Blood tests looking for markers of liver damage may be used to help assess the extent of fibrosis and liver damage.

Symptoms of signs of fibrosis

Perhaps what makes liver fibrosis so problematic is that fibrosis itself typically does not cause any symptoms. The early signs of liver fibrosis are generally only detectable via medical tests. People with fibrosis may also experience MASH symptoms such as fatigue, weight loss, or pain in the upper right abdomen, but these fatty liver disease symptoms are caused by the underlying MASH, not by the actual fibrosis.

Usually, fibrosis symptoms are only noticeable when the scarring is so advanced it causes major problems with liver function.

Symptoms of severe fibrosis or cirrhosis can include:

nausea and vomiting
reduced appetite and unexplained weight loss
pronounced fatigue
abdominal pain, especially in the upper right abdomen (where the liver is located)
swelling in the extremities and/or abdomen
itchy skin
yellowed eyes and skin (jaundice).

Treating MASH and fibrosis

MASH-related liver fibrosis treatment focuses on treating the underlying MASH by reducing the amount of fat in the liver. The less liver fat there is, the less inflammation, so reducing liver fat can slow or even reverse the vicious cycle that drives fibrosis in MASH.

The main strategies for reducing liver fat are interventions that aim to promote weight loss. The logic is fairly straightforward: reducing the total amount of fat in the body will also reduce the amount of fat in the liver.

Weight loss in MASH is often facilitated by lifestyle changes including diet and exercise, though, in some cases, more intensive interventions including bariatric surgery or appetite-lowering medicines also may be used. There isn’t any one lifestyle strategy that is always best to promote weight loss in people with MASH. Instead, the specific intervention is best tailored to the person, taking into account individual preferences and situations. It’s also worth noting too much rapid weight loss can cause health issues, so it’s important for people with MASH to work with their clinical care team to come up with a set of strategies that works for them.

Medications also may be used to help manage MASH-related fibrosis. In the U.S., there is only one specific treatment for MASH, approved for use alongside diet and exercise in people with moderate to severe liver scarring. There are also a number of experimental MASH therapies in development that have shown promising results in clinical studies.

Prevention and long-term management

The strategy for liver fibrosis prevention in MASH is to treat the underlying MASH. As discussed above, it usually focuses on lifestyle changes including diet and exercise that aim to reduce the total amount of fat in the body and relieve the inflammation that drives fibrosis progression.

These strategies also are crucial for long-term management of MASH in people who already have fibrosis. Another key part of long-term management in MASH is taking steps to reduce stress on the liver and maintain liver health, such as by cutting back or stop drinking alcohol and smoking.

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