What are MASLD and MASH, and why do they matter?

Steatotic liver diseases, defined by an accumulation of fat in liver cells, comprise an array of conditions, including MASLD and MASH. While the terms MASLD and MASH are closely related and part of the same disease spectrum, they have distinct definitions:¹

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The rising global prevalence of MASH underscores the need for early detection of MASLD to prevent progression to more severe MASH and its associated complications, such as cirrhosis and liver cancer.²

Chapter 1: What is MASLD/MASH and why is it a high-risk, progressive condition?

SC-GB-03716 Metabolism - What is MASLD-MASH and why is it a high-risk, progressive condition

Chapter 2: What are the current recommendations and key considerations for MASLD/MASH screening?

SC-GB-03714 Metabolism - What are the current recommendations and key considerations for MASLD-MASH

How many people are living with MASLD/MASH?

Approximately 1.66 billion people were estimated to live with MASLD globally in 2019, of whom up to 30% will progress to MASH.^3,4

MASH, metabolic dysfunction-associated steatohepatitis; MASLD, metabolic dysfunction-associated steatotic liver disease.

What factors lead to MASLD/MASH?

Accumulation of fat in the liver is the starting point of MASLD, leading to lipotoxicity and metabolic stress, which activates inflammatory signaling cascades that eventually lead to the more severe stages of MASH, including fibrosis and cirrhosis.⁸

Obesity is a key risk factor, contributing to an overload of fatty acids that further intensify metabolic stress and lipotoxicity.⁹ In addition, obesity can amplify hepatic inflammation through the release of pro-inflammatory cytokines, exacerbating liver damage and accelerating the progression of MASH.¹⁰

MASH, metabolic dysfunction-associated steatohepatitis.

What comorbidities are associated with MASLD/MASH?

The liver is central to metabolic health.¹² When the liver is unhealthy, excess fat and inflammation drive insulin resistance, dyslipidemia, and systemic metabolic dysfunction.¹¹ Addressing liver health is therefore pivotal in breaking the vicious cycle of metabolic disease and to improve cardiometabolic outcomes.¹¹

Most people living with MASLD or MASH are likely to have one or more related health conditions, such as obesity, dyslipidemia, hypertension, or diabetes.^13,14 Obesity is the most common comorbidity, affecting 82% of individuals with MASH and 51% with MASLD.¹⁵ Note that estimates may be even higher when obesity is defined using other anthropometric measures, such as waist circumference, rather than body mass index.¹⁶

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Prevalence of common comorbidities of MASLD/MASH

MASH, metabolic dysfunction-associated steatohepatitis; MASLD, metabolic dysfunction-associated steatotic liver disease.

Central obesity, driven by excess visceral fat, fuels fat spillover that infiltrates organs such as the liver, heart, muscles, kidneys, and the pancreas. This in turn disrupts metabolism, drives MASH, and amplifies long-term health risks. The resulting ectopic fat deposition in these organs also contributes to an increased risk of cardiovascular, renal, and metabolic conditions, such as type 2 diabetes and cardiovascular disease.^16,18

In MASH, the excessive fat accumulation in the liver increases the production of reactive oxygen species (ROS).¹⁸ The rise in ROS, and the resulting oxidative stress, triggers a cascade of inflammatory responses, which in turn act as direct causative factors for the development of cardiovascular, renal, and metabolic conditions.^19,20

CKD, chronic kidney disease; ROS, reactive oxygen species.

To learn more about obesity as a complex, chronic, relapsing metabolic disease with a significant impact on health and quality of life.

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What is the burden of MASH?

MASH is associated with a high global health and economic burden, projected to increase further in parallel with the obesity epidemic.²²

Progression of MASH with worsening fibrosis is associated with multiple adverse outcomes, including increased mortality risk, lower quality of life and work productivity, and increased healthcare costs.^23-26 The presence of comorbidities in people living with MASH increases healthcare costs even further.²⁶

Obesity

Diagnosis and Assessment

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Liver health

Screening and Diagnosis

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