Non-Alcoholic Fatty Liver Disease (NAFLD)
NICE guideline [NG49] Non-alcoholic fatty liver disease (NAFLD): assessment and management. Published: Jul 2016.
Background information has been added accordingly.
Date: 11/11/25
Background Information
Definition
NAFLD refers to the presence of hepatic steatosis in those who consume little / no alcohol (below the threshold associated with ARLD)
NAFLD is a spectrum of liver pathology, encompassing:
- Simple steatosis – reversible
- Non-alcoholic steatohepatitis (NASH) – potentially reversible
- Cirrhosis – irreversible
The terminology for NAFLD has recently been updated by the international liver disease societies (in Jun 2023):
- Non-alcoholic fatty liver disease (NAFLD) is now referred to as metabolic dysfunction-associated steatotic liver disease (MASLD)
- Non-alcoholic steatohepatitis (NASH) is now referred to as metabolic dysfunction-associated steatohepatitis (MASH)
However, NICE guidelines have not yet adopted these new terms. It is important to know both naming systems. The older terms are still commonly used in teaching, clinical notes, and exams.
Epidemiology
NAFLD is now the most common cause of chronic liver disease worldwide [Ref]
Aetiology
The cause of NAFLD is multifactorial, mainly driven by metabolic dysfunction (particularly insulin resistance, in the context of obesity and overnutrition) [Ref]
Genetic predisposition plays a significant role, with variants such as PNPLA3 and TM6SF2 increasing susceptibility to NAFLD and influencing disease progression [Ref]
Pathophysiology
Core pathophysiological mechanism of NAFLD [Ref]
- Insulin resistance → excess fat accumulation in the liver (→ hepatic steatosis)
- Over time, excessive fat deposition triggers oxidative stress and inflammation → hepatocyte injury and fibrosis
Clinical Features
Presence of the following are more suggestive of NAFLD (as opposed to general chronic liver disease):
- Obesity (esp. central obesity)
- Type 2 diabetes / pre-diabetes
- Hypertension
- Dyslipidaemia
Most other clinical features are non-specific and can be seen in any cause of chronic liver disease:
| Compensated chronic liver disease | Patients are often asymptomatic
Signs:
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| Decompensated chronic liver disease |
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Diagnosis
Although NICE does not provide a formal diagnostic checklist for NAFLD, the diagnosis is generally based on the following points (supported by international guidelines and the wider literature): [Ref]
- Evidence of hepatic steatosis
- Exclusion of secondary causes of hepatic fat accumulation
Metabolic risk factors (obesity, type 2 diabetes, dyslipidaemia) are common in NAFLD but NOT required for diagnosis
Testing for Hepatic Steatosis
1st line: liver ultrasound
- Increased echogenicity is suggestive of steatosis (the liver appears brighter than the renal cortex or spleen)
- Note that ultrasound cannot only detect steatosis, but CANNOT distinguish NAFLD from ARLD
NICE recommends offering liver ultrasound screen for NAFLD in patients with:
- Type 2 diabetes / metabolic syndrome, and
- Do not misuse alcohol
Definitive test: transjugular liver biopsy
- It is NOT performed routinely
- Liver biopsy is associated with a significant risk of morbidity and mortality
Exclusion of Secondary Causes
Main secondary causes that need to be excluded:
- ARLD (check for any significant alcohol consumption) – most common and important
- Viral hepatitis
- Medication-induced hepatic steatosis (e.g. methotrexate, amiodarone, tamoxifen, corticosteroids, valproic acid, tetracycline, certain antiretrovirals)
- Autoimmune liver disease
- Haemochromatosis
- Wilson disease
- Genetic and metabolic disorders (e.g. familial hypercholesterolaemia, glycogen storage disease, fatty acid disorders)
- Endocrine disorders (e.g. hypothyroidism, hypopituitarism, PCOS, growth hormone deficiency)
A typical chronic liver disease screening panel (in addition to standard blood test and full LFT panel):
| Test(s) | Purpose |
|---|---|
| HBsAg and Anti-HCV | Screen for viral hepatitis (Hepatitis B and C) |
| Autoimmune panel (ANA, ASMA, AMA, IgG/IgA/IgM levels) | Screen for autoimmune liver disease (AIH / PBC / PSC) |
| Ferritin + transferrin saturation | Screen for haemochromatosis |
| Caeruloplasmin | Screen for Wilson disease |
| Alpha-1 antitrypsin level | Screen for alpha-1 antitrypsin deficiency |
| HbA1c and Lipid profile | Identify metabolic syndrome risk |
Testing For Cirrhosis
ALL patients with NAFLD should be offered testing for advanced liver fibrosis (risk
- NICE recommends the ELF test
- ELF score ≥10.51 confirms advanced liver fibrosis (in those with NAFLD)
Those with advanced liver fibrosis (based on ELF score) should be referred to secondary care for transient elastography (e.g. FibroScan) to diagnose cirrhosis
Management
Management
There is no specific management for NAFLD:
- Offer lifestyle modifications (e.g. weight loss, physical activity, stop smoking) and optimise management of comorbidities (e.g. optimise diabetes control, manage concurrent cardiovascular diseases)
- Offer hepatitis A and B immunisations (to be offered to those with chronic liver disease)
- Consider pioglitazone or vitamin E in secondary and tertiary care only
Manage any complications of cirrhosis, see this article for more information.