Metabolically associated fatty liver disease: What hepatologists need to know about this systemic disease

Table 1 Change of terminology

Transcript	Years of use	Features/reasons for introduction
Non-alcoholic fatty liver disease	1980-2020	Emphasized the absence of alcohol as a cause of the disease
Metabolic (dysfunction) associated fatty liver disease	Since 2020	The emphasis is on metabolic disorders
Metabolic dysfunction-associated steatotic liver disease	Since 2023	A more precise definition is adopted in American Association for the Study of Liver Diseases/European Association for the Study of the Liver

Table 2 Comorbidities associated with metabolically associated fatty liver disease

Condition	Mechanisms/links with MAFLD	Clinical outcomes	Ref.
Type 2 diabetes mellitus	Insulin resistance, chronic hyperglycemia, lipotoxicity	Faster progression to NASH and fibrosis; higher risk of CVD	Byrne et al[263]
Chronic hepatitis B/C	Additive hepatocellular injury, inflammation, altered lipid metabolism	Increased fibrosis progression, higher risk of HCC	Choi et al[175]
Arterial hypertension	Systemic inflammation, endothelial dysfunction, insulin resistance	Greater cardiovascular morbidity, worse liver outcomes	Lonardo et al[235]
Obstructive sleep apnea	Intermittent hypoxia, oxidative stress, systemic inflammation	Worsening fibrosis; increased CVD and metabolic complications	Zhang et al[220]

NASH: Non-alcoholic steatohepatitis; CVD: Cardiovascular disease; HCC: Hepatocellular carcinoma; MAFLD: Metabolically associated fatty liver disease.

Table 3 Complications of metabolically associated fatty liver disease

Complication	Mechanisms/links with MAFLD	Clinical outcomes	Ref.
Cardiovascular disease	Atherosclerosis, dyslipidemia, systemic inflammation	Myocardial infarction, stroke, heart failure	Mantovani et al[254]
CKD	Shared risk factors (diabetes, hypertension), systemic inflammation	Higher CKD incidence, faster progression	Agustanti et al[296]
HCC	Fibrosis/cirrhosis, lipotoxicity, chronic inflammation	Increased HCC risk even without cirrhosis	Tan et al[356]
Advanced liver disease (fibrosis, cirrhosis)	Persistent steatosis, oxidative stress, inflammation	End-stage liver disease, need for transplantation	Spahis et al[73]

MAFLD: Metabolically associated fatty liver disease; CKD: Chronic kidney disease; HCC: Hepatocellular carcinoma.

Table 4 Current therapeutic approaches in Metabolically associated fatty liver disease

Therapy	Mechanisms	Clinical outcomes/limitations	Ref.
Lifestyle modification	Weight loss, improved insulin sensitivity, reduced inflammation	Most effective, especially with ≥ 10% weight loss; limited adherence	Vilar-Gomez et al[369]
Metformin	Insulin sensitizer, improves metabolic profile	Improves liver enzymes and insulin resistance, but no histological benefit	Rena et al[403]
Vitamin E	Antioxidant, reduces oxidative stress	Improves steatosis and inflammation, but not fibrosis; conflicting evidence	Yakaryilmaz et al[436]
GLP-1 receptor agonists	Weight loss, improved insulin sensitivity, reduced inflammation	Histological improvement, promising data; long-term outcomes unknown	Hartman et al[425]
SGLT2 inhibitors	Improve glycemic control, promote weight loss, reduce steatosis and fibrosis	Improve metabolic and hepatic parameters; long-term outcomes lacking	Pradhan et al[429]

SGLT2: Sodium-glucose transporter 2; GLP-1: Glucagon-like peptide-1.