Steatotic liver disease (fatty liver, MASLD)

Definition

Steatotic liver disease (SLD) is the umbrella term for excessive fat accumulation in liver cells. One of its most common forms is MASLD (metabolic dysfunction-associated steatotic liver disease): hepatic steatosis with at least one cardiometabolic risk factor and no or only minimal alcohol consumption. Since 2023 it has replaced the term NAFLD (non-alcoholic fatty liver disease).

MASH (metabolic dysfunction-associated steatohepatitis, formerly NASH) is the histologically defined inflammatory subtype with hepatocellular injury. With concomitant increased alcohol consumption (140–350 g per week in women, 210–420 g per week in men), the term MetALD is used. The new nomenclature emphasises the link with the metabolic syndrome.

Occurrence & epidemiology

MASLD, alcohol-related liver disease and MetALD are the most common causes of steatotic liver disease. MASLD is usually diagnosed at the age of about 50 to 60 years, but with the rise in obesity increasingly also in younger people and adolescents.

Aetiopathogenesis

The key to pathogenesis is insulin resistance. It increases the influx of free fatty acids to the liver and hepatic de novo lipogenesis. Reduced export of triglycerides as VLDL, increased triglyceride synthesis and genetic factors of lipid handling add to this. Ongoing inflammation activates stellate cells and leads to fibrosis; advanced MASH can progress to cirrhosis with portal hypertension and hepatocellular carcinoma. MASH can also regress to simple steatosis.

Risk factors are overweight, especially visceral obesity, type 2 diabetes or impaired glucose tolerance, dyslipidemia, arterial hypertension and the metabolic syndrome.

Clinical features

Most affected people have no symptoms, especially with simple steatosis. Some complain of fatigue, malaise or pressure in the right upper quadrant. In MASH, the liver is enlarged in about 75%. Splenomegaly is often the first sign of portal hypertension in advanced fibrosis. Cirrhosis due to MASH can also be asymptomatic and lack the usual skin signs of liver disease; hepatocellular carcinoma can also develop without cirrhosis; about half of carcinomas without cirrhosis are due to MASH.

Histology

Characteristic are large-droplet (macrovesicular) fat deposits in more than 5% of hepatocytes. In MASH, ballooned, damaged hepatocytes and lobular inflammation with mainly lymphocytes are added. Fibrosis typically shows a pericellular, chicken-wire pattern.

Diagnosis

Diagnostic criteria

The diagnosis of MASLD requires evidence of steatosis (imaging, biomarkers or biopsy) and at least one of the following cardiometabolic risk factors:

• BMI of 25 kg/m² or more (23 or more in people of Asian descent) or waist circumference of 94 cm or more (men) or 80 cm or more (women, European cut-offs)
• fasting glucose of 100 mg/dL (5.6 mmol/L) or more, HbA1c of 5.7% or more or type 2 diabetes
• blood pressure of 130/85 mmHg or more
• triglycerides of 1.7 mmol/L (150 mg/dL) or more
• HDL cholesterol of 1.0 mmol/L or less (men) or 1.3 mmol/L or less (women)

In addition, alcohol consumption may only be low (below about 20 g per day in women and 30 g per day in men); other causes such as hepatitis B and C are excluded serologically.

Laboratory tests, imaging, biopsy

• Laboratory tests: liver values are often normal; when raised, mainly the aminotransferases, with an AST/ALT ratio usually below 1, unlike in alcohol-related liver disease; ALP and GGT occasionally raised. Raised ferritin and type 2 diabetes make MASH more likely.
• Fibrosis scores such as FIB-4 or the MASLD fibrosis score identify patients at risk of advanced fibrosis.
• Imaging: ultrasound, CT and especially MRI show steatosis.
• Elastography: transient elastography, shear wave or MR elastography estimate steatosis and fibrosis; in severe obesity, ultrasound elastography is limited, whereas MR elastography is not.
• Liver biopsy: gold standard and the only method that reliably distinguishes MASLD from MASH; used when the diagnosis or stage is unclear.

Keep learning in the app

Further reading (open access)

1. MSD Manual Professional: Metabolic Dysfunction–Associated Liver Disease (MASLD)
2. Rinella ME et al. 2023: A multisociety Delphi consensus statement on new fatty liver disease nomenclature (Hepatology)
3. MSD Manual Professional: Hepatocellular Carcinoma
4. EASL-EASD-EASO-Leitlinie 2024 zur MASLD (Obes Facts 2024)

Cross-references