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Metabolic Steatohepatitis (MASH) – Causes & Treatment

Metabolic steatohepatitis (MASH) is an inflammatory liver disease involving fat accumulation and cell damage that can progress to liver cirrhosis.

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Things worth knowing about "Metabolic steatohepatitis"

Metabolic steatohepatitis (MASH) is an inflammatory liver disease involving fat accumulation and cell damage that can progress to liver cirrhosis.

What is metabolic steatohepatitis?

Metabolic steatohepatitis (abbreviated MASH, formerly known as non-alcoholic steatohepatitis or NASH) is an advanced form of metabolic dysfunction-associated steatotic liver disease (MASLD). It is characterised by excessive fat accumulation in the liver (hepatic steatosis), accompanying inflammation of the liver tissue, and damage to liver cells (hepatocyte injury). Unlike simple fatty liver, MASH can progress without treatment to advancing scar tissue formation (fibrosis), liver cirrhosis, and in severe cases to hepatocellular carcinoma (liver cancer).

Causes and risk factors

Metabolic steatohepatitis develops in connection with metabolic disorders. The most important risk factors include:

Overweight and obesity, especially visceral abdominal fat
Type 2 diabetes mellitus and insulin resistance
Metabolic syndrome (combination of high blood pressure, dyslipidaemia, elevated blood sugar, and abdominal obesity)
Elevated blood lipid levels (dyslipidaemia), particularly high triglycerides
Dietary habits high in sugar and saturated fats
Physical inactivity
Genetic predisposition (e.g., variants in the PNPLA3 gene)

The precise molecular mechanisms are complex. A so-called multiple-hit model is widely discussed, in which insulin resistance, oxidative stress, gut microbiome alterations, and genetic factors interact to cause inflammation and cell death in the liver.

Symptoms

Metabolic steatohepatitis often progresses for years without noticeable symptoms. When symptoms do occur, they may include:

Fatigue and general malaise
Dull pressure or pain in the upper right abdomen
Reduced performance and difficulty concentrating
In advanced stages: jaundice (icterus), fluid accumulation in the abdomen (ascites), increased bleeding tendency, and confusion (hepatic encephalopathy)

Diagnosis

Diagnosing MASH requires several investigative steps:

Blood tests: Liver enzymes (ALT, AST, GGT), blood lipids, blood glucose, and insulin resistance markers
Imaging: Liver ultrasound (sonography), elastography to measure liver stiffness (fibrosis assessment)
Liver biopsy: A tissue sample from the liver remains the gold standard for confirming diagnosis and assessing the degree of inflammation and fibrosis, particularly for distinguishing simple steatosis from MASH.
Non-invasive biomarkers: e.g., FibroScan, FIB-4 score, NAFLD Fibrosis Score

Treatment

Currently, a universally approved standard pharmacological therapy for MASH does not exist in all countries, although initial medications (e.g., resmetirom) have already received approval in some regions. Treatment therefore focuses primarily on lifestyle modifications:

Lifestyle changes

Weight loss: A reduction of 7–10% of body weight can significantly improve liver inflammation and fibrosis.
Dietary changes: Mediterranean diet, reduction of sugar (especially fructose) and saturated fats
Regular physical activity: At least 150 minutes of moderate exercise per week
Abstinence from alcohol or significant reduction in consumption

Pharmacological treatment options

Resmetirom (thyroid hormone receptor beta agonist): Approved in the USA for MASH with advanced fibrosis (2024)
GLP-1 receptor agonists (e.g., semaglutide): Show positive effects on liver inflammation and fibrosis in clinical studies
Management of comorbidities: Blood sugar, lipid, and blood pressure control

Endoscopic and surgical options

Bariatric surgery can significantly improve liver values and fibrosis status in patients with severe obesity.
In end-stage disease (liver cirrhosis), a liver transplantation may become necessary.

Prognosis

The prognosis depends largely on the degree of fibrosis at the time of diagnosis. Early lifestyle changes can significantly slow or even reverse the course of the disease. In patients with established cirrhosis, the risk of liver failure and liver cancer is elevated, making regular monitoring essential.

References

Rinella ME et al. - A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2023;78(6):1966-1986.
European Association for the Study of the Liver (EASL) - EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis. Journal of Hepatology. 2021;75(3):659-689.
Sanyal AJ et al. - A phase 2 randomized trial of semaglutide in nonalcoholic steatohepatitis. New England Journal of Medicine. 2021;384:1113-1124.

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