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Assessment/Diagnosis
Risk Factors
• Modifiable risk factors include visceral adiposity (defined by waist
circumference greater than 94 cm in men and 80 cm in women),
which raises MASLD risk by 7.4% to 11.4% for each 1 kg/m² increase
in BMI, as well as diets high in ultra-processed foods, saturated fats,
fructose, and sugar-sweetened beverages, which exacerbate hepatic
lipid accumulation.
• Physical inactivity impairs insulin sensitivity and f ree fatty
acid oxidation, while comorbidities such as T2DM and
hypertension synergistically accelerate disease progression.
Nonmodif iable risk factors comprise genetic polymorphisms
in patatin-like phospholipase domain-containing 3 (PNPLA3)
and transmembrane 6 superfamily member 2 (TM6SF2) gene
mutations, increasing susceptibility, as well as older age (peak
prevalence 50–60 years) and higher incidence among those of
Hispanic ethnicity.
Additional Metabolic Complication of Obesity
Metabolic Dysfunction-Associated Steatotic Liver Disease
➤ MASLD, present in up to 90% of individuals with severe obesity,
reflects the hepatic manifestation of MetS and progresses from
steatosis to cirrhosis due to obesity-driven insulin resistance,
visceral adiposity, and associated metabolic and genetic risk factors.
➤ Clinical Manifestations
• MASLD is mainly asymptomatic and often discovered incidentally.
Patients may present with nonspecif ic symptoms such as
fatigue related to sarcopenia, right upper-quadrant discomfort
f rom Glisson capsule distension, and diminished health-related
quality of life. Cardiovascular complications are common and
include accelerated atherosclerosis, coronary artery disease, and a
signif icantly increased risk of heart failure (up to 2.5 times higher in
those with advanced f ibrosis). Hepatic manifestations include mild
elevations in liver enzymes (ALT/AST typically <2 times the upper
limit of normal), hepatomegaly, and progression to cirrhosis in
approximately 5% to 20% of cases.
