Definition of MASLD
MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease) is defined as the presence of excess triglyceride storage in the liver (hepatic steatosis) in the presence of at least one cardiometabolic risk factor and the absence of harmful alcohol intake (≤20 g/day in females, ≤30 g/day in males). 1
Core Diagnostic Criteria
MASLD requires two essential components to be present simultaneously: 1
- Hepatic steatosis confirmed by imaging (ultrasound, CT, MRI) or liver biopsy 2
- At least one cardiometabolic risk factor including: 1, 3
- Overweight or obesity
- Type 2 diabetes or impaired glucose metabolism
- Hypertension
- Dyslipidemia (hypertriglyceridemia or low HDL-cholesterol)
- Limited alcohol consumption below harmful thresholds (≤140 g/week for women, ≤210 g/week for men) 4
Terminology Update and Context
MASLD replaces the outdated term "non-alcoholic fatty liver disease" (NAFLD) and represents a fundamental shift toward recognizing the metabolic basis of this condition. 1
The term MASLD sits within the broader umbrella of steatotic liver disease (SLD), which also includes: 1
- MetALD (MASLD with moderate alcohol intake: 20-50 g/day in females, 30-60 g/day in males)
- Alcohol-related liver disease (ALD) (>50 g/day in females, >60 g/day in males)
- Specific etiologies (drug-induced, monogenic diseases)
- Cryptogenic SLD
Disease Spectrum
MASLD encompasses a spectrum of liver conditions ranging from simple steatosis to life-threatening complications: 1
- MASL (Metabolic dysfunction-associated steatotic liver): isolated liver steatosis without inflammation
- MASH (Metabolic dysfunction-associated steatohepatitis, previously NASH): characterized by hepatocellular ballooning and lobular inflammation on histology 1, 5
- Fibrosis: progressive scarring of liver tissue
- Cirrhosis: end-stage liver scarring
- Hepatocellular carcinoma (HCC): MASH-related liver cancer 1
Clinical Significance and Epidemiology
MASLD has become the most common chronic liver disease globally, affecting more than a quarter of the world's population, with prevalence expected to continue rising due to the obesity pandemic. 1, 3, 6
The disease carries substantial morbidity and mortality through: 1
- Cardiovascular events (the leading cause of death in MASLD patients)
- Chronic kidney disease
- Hepatic and extrahepatic malignancies
- Liver-related outcomes including liver failure and HCC
Pathophysiologic Mechanisms
The development of MASLD involves multiple interconnected pathways: 3, 7
- Insulin resistance as a central driver
- Dysregulation of lipid metabolism: increased hepatic fatty acid entry from adipose tissue, increased fatty acid synthesis, reduced fatty acid oxidation
- Chronic inflammation and oxidative stress
- Mitochondrial dysfunction
- Gut microbiota alterations
- Genetic and epigenetic factors
Critical Distinction: MASLD vs MetALD
Accurate quantification of alcohol consumption is essential to differentiate MASLD from MetALD, as MetALD carries a worse prognosis despite identical cardiometabolic risk factor prevalence. 2
Use validated psychometric instruments (such as AUDIT-C) and biomarkers rather than relying solely on patient self-report, as underreporting of alcohol consumption is common. 2