About This Page
This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
The Bottom Line
- NAFLD = hepatic steatosis (≥5% fat) without excessive alcohol intake — now the commonest liver disease in the UK (~25–30% prevalence)
- Spectrum: simple steatosis (benign) → NASH (inflammation + hepatocyte damage) → fibrosis → cirrhosis → HCC
- Strongly associated with metabolic syndrome: obesity, T2DM, hypertension, dyslipidaemia
- Assess fibrosis risk: use FIB-4 score (age, AST, ALT, platelets) or NAFLD fibrosis score → FibroScan if intermediate/high risk
- Treatment: weight loss of ≥10% body weight is the most effective intervention — no licensed pharmacological therapy for NAFLD itself
Overview
Non-alcoholic fatty liver disease (NAFLD) — recently also termed metabolic dysfunction-associated steatotic liver disease (MASLD) — is defined as hepatic steatosis (≥5% of hepatocytes containing fat on histology or imaging) in the absence of significant alcohol consumption (<20 g/day women, <30 g/day men) or other secondary causes. The condition is driven by insulin resistance and is considered the hepatic manifestation of metabolic syndrome. Most patients have simple steatosis, which is benign. Approximately 20% develop NASH (non-alcoholic steatohepatitis), which can progress to fibrosis, cirrhosis, and hepatocellular carcinoma.
Epidemiology
NAFLD is the most common liver disease in the UK, affecting approximately 25–30% of the adult population. Prevalence rises to 70–80% in people with obesity and 50–70% in people with T2DM. NASH is present in approximately 5–6% of the general population. NAFLD is now the second most common indication for liver transplantation in the UK and is projected to become the leading cause. The primary cause of death in NAFLD patients is cardiovascular disease, not liver disease.
Clinical Features
Symptoms
Usually asymptomatic — often detected incidentally on USS or blood tests
Fatigue (non-specific)
Vague RUQ discomfort
Features of metabolic syndrome: central obesity, known T2DM, hypertension
Symptoms of advanced liver disease if cirrhosis has developed
Signs
Hepatomegaly (smooth, non-tender in simple steatosis)
Central/visceral obesity
Acanthosis nigricans (insulin resistance marker)
Signs of cirrhosis if advanced: spider naevi, palmar erythema, splenomegaly, ascites
Investigations
First-line
LFTsALT typically mildly raised (usually <100 IU/L). GGT may be elevated. Can be entirely normal even with significant fibrosis
FIB-4 scoreNon-invasive fibrosis assessment using age, AST, ALT, platelet count. <1.3 = low risk; 1.3–2.67 = intermediate (needs further assessment); >2.67 = high risk
Metabolic screenHbA1c, fasting glucose, lipid profile, blood pressure — assess and manage cardiovascular risk
Second-line
FibroScan (transient elastography)For intermediate/high FIB-4 scores — determines degree of fibrosis. <8 kPa = low fibrosis; >12 kPa = suggests advanced fibrosis/cirrhosis
Abdominal USSBright (hyperechogenic) liver — suggests steatosis. Cannot distinguish simple steatosis from NASH
Liver screenExclude other causes of chronic liver disease: hepatitis B/C, autoimmune (ANA, SMA, immunoglobulins), haemochromatosis (ferritin, transferrin sat), Wilson disease (if <40 years), alpha-1-antitrypsin
Specialist
Liver biopsyGold standard for distinguishing NASH from simple steatosis and staging fibrosis. Reserved for diagnostic uncertainty or clinical trials
ELF (Enhanced Liver Fibrosis) testBlood biomarker panel (HA, PIIINP, TIMP-1) — additional non-invasive fibrosis tool
Management
NICE NG49 (NAFLD), 20161
Lifestyle modification (cornerstone)
- Weight loss: target ≥10% body weight — shown to resolve NASH and improve fibrosis
- Mediterranean diet: high in fruit, vegetables, olive oil, nuts; low in refined carbohydrates and saturated fat
- Regular exercise: ≥150 min/week moderate-intensity — improves hepatic steatosis independent of weight loss
- Avoid alcohol excess (even moderate alcohol may accelerate progression)
2
Cardiovascular risk management
- Cardiovascular disease is the leading cause of death in NAFLD — aggressively manage risk factors
- Statin therapy: safe in NAFLD/NASH (NICE confirms statins are NOT contraindicated in liver disease)
- Antihypertensive therapy as indicated
- Optimise glycaemic control in T2DM
3
Pharmacological (limited)
- No NICE-approved drug specifically for NAFLD/NASH
- Pioglitazone or vitamin E may be considered for biopsy-proven NASH with significant fibrosis (off-label, specialist decision)
- GLP-1 receptor agonists (e.g. semaglutide) showing promise in trials for NASH resolution — watch this space
- Resmetirom (thyroid hormone receptor agonist) approved by FDA in 2024 for NASH with fibrosis — not yet UK licensed
4
Monitoring and referral
- Repeat FIB-4 every 3 years (NICE NG49)
- Refer to hepatology if: advanced fibrosis (FibroScan >12 kPa), diagnostic uncertainty, co-existing liver disease
- If cirrhosis develops: HCC surveillance (6-monthly USS), variceal screening (OGD)
Complications
- Cirrhosis: ~5–10% of NASH patients progress over 10–20 years
- Hepatocellular carcinoma: Can develop in NAFLD even without cirrhosis (though much rarer)
- Cardiovascular disease: Leading cause of death in NAFLD — the liver disease itself is a cardiovascular risk marker
- Type 2 diabetes: NAFLD and T2DM are bidirectional — each worsens the other
- CKD: NAFLD is independently associated with chronic kidney disease
UKMLA Exam Tips
- 1NAFLD is the commonest liver disease in the UK (~25–30% adults). Cardiovascular disease, NOT liver disease, is the leading cause of death
- 2FIB-4 <1.3 = LOW risk of fibrosis → reassure and repeat in 3 years
- 3Statins are SAFE in NAFLD/NASH — do NOT withhold (common misconception)
- 4Weight loss ≥10% = most effective treatment. There is no NICE-approved drug for NAFLD
- 5USS shows bright liver but CANNOT distinguish simple steatosis from NASH — only biopsy can definitively distinguish
- 6Normal ALT does NOT exclude significant fibrosis — fibrosis assessment (FIB-4/FibroScan) is essential
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