Metabolic dysfunction-associated steatotic liver disease (MASLD), known for decades as non-alcoholic fatty liver disease (NAFLD), is the most prevalent chronic liver condition in the world, affecting an estimated 25–30% of the adult population generally and as much as 75–90% of people with obesity or type 2 diabetes. MASLD is defined as fat accumulation in more than 5% of liver cells, in the absence of significant alcohol consumption or other secondary causes.
The condition spans a range: simple fat accumulation at one end, then metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH), fibrosis, cirrhosis and liver cancer. It is widely understood as the hepatic expression of metabolic syndrome, tightly bound up with insulin resistance, visceral obesity, elevated triglycerides, hypertension and impaired blood sugar regulation.
Crucially, early-stage MASLD is reversible given targeted lifestyle and nutritional intervention.
In 2023, a multi-society consensus renamed NAFLD to MASLD, and NASH to MASH, to reflect the metabolic drivers now understood to underlie the disease. Both names describe the same condition, and NAFLD still appears throughout older research and in everyday clinical use.
Fatty liver symptoms and early diagnostic indicators
Early MASLD is largely silent, and most cases surface incidentally, through abnormal liver enzymes or imaging carried out for unrelated reasons.
Where symptoms do occur, they are non-specific.
Hepatic symptoms:
Right upper quadrant discomfort or heaviness
Fatigue — among the most frequently reported symptoms
Nausea, particularly after fatty meals
Metabolic signs:
Acanthosis nigricans — dark, velvety skin in the skin folds; a marker of insulin resistance
Multiple skin tags — independently associated with insulin resistance and metabolic syndrome
Abdominal obesity: waist circumference predicts MASLD better than BMI does
Laboratory markers:
ALT: elevated in 50–70% of MASLD patients.
GGT — an early and sensitive marker of hepatic oxidative stress.
Fasting triglycerides: reflect impaired hepatic fat export; both a cause and a consequence of MASLD.
Fasting insulin / HOMA-IR: a HOMA-IR above 2.5 is associated with significantly elevated MASLD risk.
Uric acid — an independent risk factor, likely acting through fructose-driven mechanisms and mitochondrial oxidative stress.
Imaging: hepatic ultrasound is the standard first-line investigation. FibroScan offers greater sensitivity for mild steatosis, plus non-invasive fibrosis staging.
Disease spectrum and staging
MASLD progresses along a histological spectrum:
Simple steatosis — fat accumulation without significant inflammation or scarring. Largely reversible, with low risk of progression on its own.
MASH: steatosis accompanied by lobular inflammation, hepatocyte injury and early fibrosis. Affects 10–25% of MASLD patients.
Fibrosis — progressive scarring driven by chronic inflammation. Fibrosis stage is the strongest predictor of both liver-related and all-cause mortality.
Cirrhosis — extensive scarring with loss of normal liver architecture.
Pathophysiology: the multiple parallel-hit model
1. Insulin resistance and de novo lipogenesis
Insulin resistance drives excess fat production in the liver — de novo lipogenesis — while simultaneously reducing fatty acid oxidation. Fructose is a particularly potent driver: unlike glucose it bypasses normal glycolytic regulation and is metabolised almost entirely in the liver, activating fat synthesis pathways directly.
2. Gut-liver axis dysfunction
Around 70% of the liver's blood supply arrives via the portal vein draining the intestine. Where the gut barrier is compromised (“leaky gut”), bacterial lipopolysaccharides (LPS) enter portal circulation and activate hepatic immune cells, setting off the inflammatory cascade at the centre of MASH progression. Gut microbiome composition is significantly altered in MASLD, with fewer barrier-protective species and more LPS-producing bacteria.
3. Mitochondrial dysfunction and oxidative stress
Impaired mitochondrial fat burning, together with increased production of reactive oxygen species (ROS), drives the shift from simple steatosis to MASH, injuring hepatocytes and activating the stellate cells that generate fibrosis.
4. Visceral fat inflammation and lipotoxicity
Visceral adipose tissue releases surplus free fatty acids and inflammatory cytokines (TNF-α, IL-6) into portal circulation, damaging hepatocytes directly. Adiponectin, which is anti-inflammatory and markedly reduced in visceral obesity, is independently associated with MASH severity.
5. Endocrine disruption
Hypothyroidism reduces hepatic fatty acid oxidation and fat export, promoting steatosis. A meta-analysis confirmed significantly elevated MASLD risk among hypothyroid patients.
Evidence-based interventions
Early-stage MASLD responds well to targeted intervention. A Mediterranean-style diet has the strongest evidence base of any dietary pattern studied, and regular exercise, resistance training in particular, improves insulin sensitivity independent of weight loss. Several nutrients have trial evidence behind them too, including marine omega-3 fatty acids, silymarin, choline and targeted probiotics.
For the full evidence-based reversal protocol, diet, exercise and supplementation specifics included, see our Liver Health Master Class.
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