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MASH: Causes, Symptoms and Treatment

MASH (Metabolic-associated Steatohepatitis) is an advanced liver disease involving fat accumulation, inflammation, and liver cell damage, which can progress to cirrhosis.

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Things worth knowing about "MASH"

MASH (Metabolic-associated Steatohepatitis) is an advanced liver disease involving fat accumulation, inflammation, and liver cell damage, which can progress to cirrhosis.

What is MASH?

MASH stands for Metabolic-associated Steatohepatitis. It is an advanced form of metabolic dysfunction-associated steatotic liver disease (MASLD), characterized not only by excessive fat accumulation in the liver, but also by inflammation and liver cell injury (hepatocyte damage). MASH replaces the older term NASH (Non-alcoholic Steatohepatitis), reflecting updated scientific understanding that places metabolic dysfunction at the center of the disease process.

Causes and Risk Factors

The development of MASH is closely linked to the metabolic syndrome. Key risk factors include:

Overweight and obesity, particularly excess abdominal fat
Type 2 diabetes and insulin resistance
Dyslipidemia (elevated blood fat levels)
High blood pressure (arterial hypertension)
Genetic predisposition (e.g., variants in the PNPLA3 gene)
Diet high in sugar, saturated fats, and ultra-processed foods
Physical inactivity

Symptoms

In its early stages, MASH is often asymptomatic. As the disease progresses, patients may experience:

Fatigue and general lack of energy
Dull pressure or discomfort in the upper right abdomen
Reduced physical performance
In advanced stages: yellowing of the skin and eyes (jaundice), fluid accumulation in the abdomen (ascites), and confusion (hepatic encephalopathy)

Diagnosis

The diagnosis of MASH typically involves several steps:

Blood tests: Elevated liver enzymes (ALT, AST, GGT) may suggest liver damage, but are not specific to MASH.
Imaging: Ultrasound, MRI, or elastography techniques (e.g., FibroScan) can assess fat accumulation and liver stiffness.
Liver biopsy: Considered the gold standard for confirming the diagnosis; it allows assessment of inflammation, fibrosis, and cell damage.
Non-invasive biomarkers: Tools such as the Enhanced Liver Fibrosis (ELF) Score or FIB-4 index can estimate the degree of fibrosis without a biopsy.

Treatment

Lifestyle Changes

The cornerstone of MASH management is a consistent lifestyle modification:

Weight loss of at least 7–10 % of body weight has proven benefits on liver inflammation and fibrosis.
Mediterranean-style diet rich in vegetables, fruits, legumes, olive oil, and fish
Regular physical activity (at least 150 minutes of moderate exercise per week)
Complete avoidance of alcohol

Pharmacological Treatment

As of 2024, Resmetirom (brand name: Rezdiffra) became the first drug specifically approved by the US Food and Drug Administration (FDA) for MASH with moderate to advanced fibrosis. Additional treatment approaches include:

Vitamin E: Recommended for non-diabetic patients with biopsy-confirmed MASH
GLP-1 receptor agonists (e.g., semaglutide): Have shown positive effects on liver inflammation and fibrosis
Managing underlying conditions: Optimal control of diabetes, blood pressure, and cholesterol levels

Advanced Liver Disease

In end-stage liver failure, a liver transplant may be necessary. MASH has become one of the leading indications for liver transplantation worldwide.

Prognosis and Disease Progression

Without treatment, MASH can progress over years to liver fibrosis (scarring), liver cirrhosis, and ultimately hepatocellular carcinoma (liver cancer). However, with early diagnosis and consistent lifestyle changes, the course of the disease can be slowed or even reversed.

References

European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO): EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). Journal of Hepatology, 2024.
Rinella, M.E. et al.: A multi-society Delphi consensus statement on new fatty liver disease nomenclature. Hepatology, 2023.
Harrison, S.A. et al.: Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. The New England Journal of Medicine, 2024.

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