Fatty Liver Disease (NAFLD/MASLD)

What is fatty liver disease?

Non-alcoholic fatty liver disease (NAFLD): now renamed metabolic dysfunction-associated steatotic liver disease (MASLD), is characterised by excess fat accumulation in liver cells (hepatocytes) in people who drink little or no alcohol. It ranges from simple steatosis (fat only, benign) to NASH (non-alcoholic steatohepatitis, fat plus inflammation) to fibrosis and cirrhosis. It is strongly linked to obesity, type 2 diabetes, insulin resistance and metabolic syndrome.

Fatty liver grading

Blood test results in fatty liver

What causes fatty liver?

• Obesity, especially central/abdominal fat
• Type 2 diabetes and insulin resistance
• High-carbohydrate and high-fructose diet (soft drinks, refined carbs)
• High triglycerides (hypertriglyceridaemia)
• Rapid weight loss or starvation (mobilises fat to the liver)
• Certain medications: corticosteroids, amiodarone, tamoxifen, methotrexate
• Hypothyroidism (slows fat metabolism)

How to reverse fatty liver

Questions to ask your doctor

• Do I need a liver ultrasound to grade my fatty liver?
• Should I have a FibroScan (liver elastography) to assess fibrosis?
• Is my blood sugar or insulin resistance contributing?
• What diet changes will have the fastest impact?
• When should I retest my liver enzymes?

References

The clinical information on this page is drawn from peer-reviewed sources indexed by the US National Library of Medicine. Links go to the source so you can read it yourself.

1. Liver Function Tests. In: StatPearls. Treasure Island (FL): StatPearls Publishing. NCBI Bookshelf NBK482489

References

Sources cited on this page. PubMed links open the original abstract.

1. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328–357. PMID 29427967 · doi:10.1002/hep.29367

NAFLD versus NASH – the crucial distinction

Non-alcoholic fatty liver disease (NAFLD) is an umbrella term covering a spectrum:

• Simple steatosis (NAFL): Fat accumulation in more than 5% of hepatocytes without significant inflammation or cell injury. This is benign in the majority – most patients do not progress to cirrhosis. The primary risk is that it can progress to NASH.
• Non-alcoholic steatohepatitis (NASH): Fat plus inflammation plus hepatocyte injury (ballooning degeneration). Approximately 15–20% of those with simple steatosis develop NASH. Of those with NASH, approximately 15–25% progress to cirrhosis over 10–20 years. NASH is now the second most common indication for liver transplant in the USA and is projected to become the leading indication in the next decade.

Blood tests alone cannot reliably distinguish simple steatosis from NASH – liver biopsy remains the gold standard. Non-invasive alternatives include the FIB-4 score and NFS (NAFLD fibrosis score) for identifying advanced fibrosis, and the NASHscreen biomarker panel (cytokeratin-18 fragments) for identifying NASH – though none fully replace biopsy for definitive histological classification.

Blood tests and their limitations in NAFLD

• ALT and AST: Elevated in 30–80% of NAFLD cases. However, a normal ALT does not exclude NAFLD or even NASH – up to 30% of patients with histologically confirmed NASH have normal liver enzymes. ALT is therefore a poor screening tool for NAFLD.
• FIB-4 score: Calculated as (age × AST) ÷ (platelets × √ALT). Below 1.3 = low fibrosis risk (F0–F1); above 2.67 = high fibrosis risk (F3–F4). NICE and British Society of Gastroenterology recommend FIB-4 as the first-line non-invasive fibrosis tool in primary care for all patients with suspected NAFLD.
• GGT: Often elevated in fatty liver, particularly with metabolic syndrome. A GGT above the upper limit of normal in a patient with raised BMI, diabetes, or hypertriglyceridaemia supports NAFLD as the diagnosis.
• Ferritin: Elevated in NAFLD (as an acute phase protein and iron accumulation marker) – do not confuse with haemochromatosis, which also causes elevated ferritin but is distinguished by high transferrin saturation and HFE gene mutation.

The only proven treatment – and what guidelines recommend

There is currently no approved pharmacological treatment for NAFLD. The only intervention with proven efficacy for all stages of NAFLD is sustained weight loss: a 5–7% reduction in body weight reduces liver fat; a 7–10% reduction can resolve NASH histologically; weight loss above 10% can reverse fibrosis. The Liver4Life trial demonstrated that a very low-calorie diet (800–900 kcal/day) producing 10–15% weight loss led to NASH resolution in the majority. Bariatric surgery in morbidly obese patients produces the most sustained weight loss and the most dramatic NAFLD improvement. GLP-1 receptor agonists (semaglutide) are in phase 3 trials for NASH – early results suggest significant histological improvement.