Metabolic Dysfunction–Associated Steatohepatitis (MASH)

A progressive form of fatty liver disease caused by metabolic dysfunction, inflammation, and liver cell injury — strongly linked to obesity, insulin resistance, and type 2 diabetes.

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Overview

Metabolic dysfunction-associated steatohepatitis (MASH), formerly called nonalcoholic steatohepatitis or NASH, is the inflammatory, progressive form of fatty liver disease. In MASH, fat accumulation in the liver is accompanied by inflammation and liver-cell injury, which can lead to scarring (fibrosis), cirrhosis, liver failure and liver cancer (Rinella et al., multisociety nomenclature consensus, Hepatology, 2023).

MASH is part of a broader spectrum called metabolic dysfunction-associated steatotic liver disease (MASLD), which affects roughly one in three adults worldwide and is closely linked to obesity, type 2 diabetes and insulin resistance. Most people with MASLD have simple fatty liver, but a substantial minority have MASH, and fibrosis stage is the single most important predictor of long-term outcomes (Rinella et al., AASLD Practice Guidance, Hepatology, 2023).

MASH is usually silent until it is advanced, which is why screening people at risk matters. The encouraging news is that MASH is reversible: weight loss of 10% or more resolves MASH in most patients and can reverse fibrosis (Vilar-Gomez et al., Gastroenterology, 2015), and new medications and bariatric surgery offer powerful options for patients who need more help.

From NAFLD and NASH to MASLD and MASH

In 2023, international liver societies replaced the terms nonalcoholic fatty liver disease (NAFLD) and NASH with MASLD and MASH (Rinella et al., Hepatology, 2023). The new names emphasize that the condition is driven by metabolic dysfunction, such as obesity, type 2 diabetes, high blood pressure and abnormal cholesterol, rather than defined by the absence of alcohol. Patients who also drink moderate amounts of alcohol fall into a combined category called MetALD.

Stages of Fatty Liver Disease

Steatosis: fat in more than 5% of liver cells without significant inflammation
MASH: fat plus inflammation and liver-cell injury
Fibrosis: scarring, graded F0 (none) to F4 (cirrhosis)
Cirrhosis: extensive scarring that distorts the liver's structure

Causes

Excess body fat, particularly visceral (abdominal) fat
Insulin resistance, which drives fat production and storage in the liver
Type 2 diabetes
High triglycerides and low HDL cholesterol
Diets high in fructose, sugary drinks and ultra-processed foods
Genetic factors, including variants in the PNPLA3 gene that are more common in Hispanic populations
Sleep apnea, which may promote liver injury

MASH sits at the center of a cluster of metabolic problems. People with insulin resistance, metabolic syndrome or sleep apnea are more likely to have fatty liver, and fatty liver itself worsens insulin resistance, creating a cycle that effective weight loss can break.

Risk Factors

Obesity, especially severe obesity
Type 2 diabetes, one of the strongest predictors of advanced fibrosis (Rinella et al., AASLD Practice Guidance, Hepatology, 2023)
Metabolic syndrome
Hispanic ethnicity
Older age
Alcohol use, which adds to liver injury
Family history of cirrhosis

Who It Affects

MASH most often affects adults with obesity and type 2 diabetes, and a large proportion of patients undergoing bariatric surgery have fatty liver disease. In South Florida, the high prevalence of obesity and diabetes and the genetic predisposition in Hispanic communities make MASH particularly important.

Children and teenagers with obesity can also develop MASH, sometimes with significant fibrosis at a young age, which makes early treatment of childhood obesity especially important.

Complications

Fibrosis and cirrhosis
Liver failure and need for transplantation; MASH is now among the leading causes of liver transplantation in the United States
Liver cancer (hepatocellular carcinoma), which can occur even before cirrhosis
Cardiovascular disease, the leading cause of death in people with MASLD (Rinella et al., AASLD Practice Guidance, Hepatology, 2023)
Chronic kidney disease

Because cardiovascular disease is the most common cause of death in people with fatty liver disease, managing blood pressure, cholesterol and diabetes is as important as treating the liver itself.

Symptoms

Most people have no symptoms until the disease is advanced. When present, symptoms include:

Fatigue
Vague discomfort in the upper right abdomen
In cirrhosis: swelling of the abdomen or legs, yellowing of the skin, easy bruising, confusion and vomiting blood

Diagnosis

Guidelines recommend a stepwise approach to identify patients with significant fibrosis (Rinella et al., AASLD Practice Guidance, Hepatology, 2023):

Liver tests and imaging often first show fatty liver, though liver enzymes can be normal even with MASH.
FIB-4 score: a simple calculation from age, liver enzymes and platelet count; a low score makes advanced fibrosis unlikely.
Elastography (FibroScan or MR elastography) measures liver stiffness when FIB-4 is not low.
Blood-based fibrosis tests such as the ELF test
Liver biopsy, the reference standard for diagnosing MASH and staging fibrosis, used when results are uncertain or treatment decisions depend on it. During bariatric surgery, a liver biopsy can be taken at the same time.

Liver enzyme levels are a poor guide to the severity of MASH: many patients with significant fibrosis have normal ALT and AST. This is why noninvasive fibrosis scores and elastography are recommended for people at risk, regardless of enzyme levels (Rinella et al., Hepatology, 2023).

Differential Diagnosis

Alcohol-related liver disease
Viral hepatitis B or C
Autoimmune hepatitis
Hemochromatosis and Wilson disease
Medication-induced liver injury

Lifestyle Modifications

Lose weight: in a landmark study, losing 10% or more of body weight resolved MASH in about 90% of patients and reversed fibrosis in nearly half (Vilar-Gomez et al., Gastroenterology, 2015).
Follow a Mediterranean-style eating pattern rich in vegetables, olive oil, fish and whole grains.
Eliminate sugar-sweetened beverages and limit added fructose.
Exercise regularly, which reduces liver fat even without weight loss.
Limit or avoid alcohol, especially with advanced fibrosis.
Control diabetes, cholesterol and blood pressure.
Coffee consumption has been associated with lower fibrosis risk.

What a Liver-Friendly Day Looks Like

Breakfast: eggs or Greek yogurt with berries instead of pastries or sweetened cereal
Lunch: a large salad or vegetables with grilled fish or chicken and olive oil
Snack: a handful of nuts or vegetables with hummus
Dinner: lean protein, vegetables and a small portion of whole grains or legumes
Drinks: water, unsweetened coffee or tea; no soda, juice or sweetened drinks

Treatment Options

Medications

Resmetirom: the first medication approved specifically for MASH with moderate to advanced fibrosis, after a trial showed MASH resolution and fibrosis improvement compared with placebo (Harrison et al., MAESTRO-NASH trial, New England Journal of Medicine, 2024)
GLP-1 receptor agonists: semaglutide resolved MASH in a majority of patients in a phase 2 trial (Newsome et al., New England Journal of Medicine, 2021) and has since been approved for MASH with moderate to advanced fibrosis. Tirzepatide is also being studied. See medical weight loss.
Pioglitazone and vitamin E in selected patients (Rinella et al., AASLD Practice Guidance, Hepatology, 2023)

Bariatric Surgery

Bariatric surgery is one of the most effective treatments for MASH. In a prospective study with liver biopsies, MASH resolved in 84% of patients five years after surgery and fibrosis decreased in about 70% (Lassailly et al., Gastroenterology, 2020). In a large matched study, bariatric surgery was associated with an 88% lower risk of major adverse liver outcomes compared with nonsurgical care (Aminian et al., SPLENDOR study, JAMA, 2021). See bariatric surgery.

Advanced Disease

Patients with cirrhosis need cancer and varices surveillance, and those with liver failure may need transplantation. Bariatric surgery in compensated cirrhosis is possible in experienced centers with careful selection.

Choosing the Right Treatment

For patients with MASH and obesity, the most effective strategy is substantial, sustained weight loss. Lifestyle change alone works for some, but most people find it difficult to lose and maintain 10% of their body weight. Medications that produce larger weight loss, and bariatric surgery for those who qualify, offer the best chance of reversing liver damage. Patients with type 2 diabetes benefit from choosing diabetes medications that also help the liver, such as GLP-1 receptor agonists and pioglitazone (Rinella et al., Hepatology, 2023).

When to See a Doctor

Ask your doctor about liver screening if you have type 2 diabetes, obesity, or two or more metabolic risk factors, or if a scan or blood test has shown fatty liver or elevated liver enzymes.

If you are considering bariatric surgery, your team will evaluate your liver beforehand; fatty liver often causes an enlarged liver, which is why a short preoperative diet is used to shrink it and make surgery safer.

When to Seek Treatment

Seek urgent care for yellowing of the skin or eyes, vomiting blood, black stools, confusion or rapidly increasing abdominal swelling.

Long-Term Outlook

Sustained weight loss and control of diabetes and cholesterol are the keys to long-term liver health. Periodic fibrosis testing tracks progress and guides treatment decisions.

Patients with cirrhosis require lifelong surveillance with ultrasound every six months for liver cancer, even after successful weight loss.

Prognosis

The prognosis depends mainly on fibrosis stage. MASH without significant fibrosis can be reversed with weight loss, while patients with advanced fibrosis face higher risks of cirrhosis and liver cancer but can still improve with treatment (Vilar-Gomez et al., Gastroenterology, 2015) (Lassailly et al., Gastroenterology, 2020).

Even patients with advanced fibrosis can see regression after effective weight loss, particularly after bariatric surgery, which is why it is never too late to treat the underlying metabolic disease.

Why Choose Dr. de la Cruz-Muñoz

Fatty liver disease is one of the most common conditions among patients with obesity, and one of the most responsive to effective weight loss. Dr. de la Cruz-Muñoz is a board-certified metabolic and bariatric surgeon who offers medical weight loss with GLP-1 medications and bariatric surgery, with liver biopsy at the time of surgery when appropriate, in coordination with hepatology.

Dr. de la Cruz-Muñoz co-authored research on ethnic and gender differences in the prevalence of steatohepatitis among bariatric surgery patients (Messiah et al., Bariatric Surgical Practice and Patient Care, 2016), reflecting the diverse South Florida population he serves.

Dr. de la Cruz-Muñoz has been performing bariatric surgery for over 25 years and has completed more than 9,000 bariatric operations — a volume few surgeons reach.