Non-alcoholic fatty liver disease (NAFLD)

Definition

Non-alcoholic fatty liver disease (NAFLD) refers to excess fat (triglyceride) accumulation in the liver (steatosis), in the absence of excessive alcohol consumption (<2.5 units/day for women or <3.75 units/day for men) or other secondary causes (e.g. drugs like amiodarone or tamoxifen or PCOS).
NAFLD is diagnosed by the presence of an echobright liver on ultrasound in the absence of excessive alcohol consumption.

NAFLD is causally linked to insulin resistance, obesity and the metabolic syndrome.

Majority of NAFLD case involve simple steatosis (good prognosis), minority involve non-alcoholic steatohepatitis (NASH) (high risk of liver fibrosis, cirrhosis, or rarely cancer).

NAFLD is the commonest cause of abnormal liver function test (LFT) results in the UK.

Risk factors

Hypertension
Impaired glucose regulation or type 2 diabetes mellitus
Central obesity (BMI>30, waist circumference>94 cm in men or 80 cm in women)
Hyperlipidaemia

Complications

METABOLIC: cardiovascular disease, impaired glucose regulation, and type 2 diabetes mellitus.

LIVER: portal hypertension, variceal haemorrhage, liver failure, hepatocellular carcinoma, and sepsis.

Symptoms and Signs

NAFLD is often asymptomatic, but may occasionally cause non-specific symptoms of fatigue, general malaise, and abdominal discomfort.

Diagnosis

Criteria:

  1. Presence of risk factors for NAFLD

  2. Elevated LFTs (ALT x3 upper limit)

  3. Ultrasound abdomen: fatty liver changes

  4. Negative liver aetiology screen

Further assessment

METABOLIC screen:

Manage risks of hypertension, diabetes, hyperlipidaemia and cardiovascular disease using validated tools (e.g. QRISK3).

LIVER:

Assess the risk of liver fibrosis

1. Calculate fibrosis-4 (FIB-4) or NAFLD Fibrosis Score (NFS) to determine the risk of advanced liver fibrosis

A low FIB-4 (<1.3 for those aged <65 years or <2.0 for those >65 years) or low NFS (<−1.455 for those aged <65 years or <0.12 for those >65 years) excludes likelihood of advanced liver fibrosis (low false-negative rate) and can be managed in primary care

A non-low FIB-4 or NFS score indicates a risk of advanced liver fibrosis, and necessitates quantitative assessment of liver fibrosis

Tests:

  1. Serum enhanced liver fibrosis (ELF) measurement

  2. Imaging: Fibroscan acoustic radiation force impulse (ARFI) elastography

If ELF>9.5 or ARFI>7.8kPa or invalid scan then individual is considered high risk of advanced liver fibrosis and should be referred to Hepatology.

The FIB-4 score should be calculated every two to five years in patients with NAFLD; refer to a specialist if the score increases above the age-related cut-off.

NAFLD Fibrosis Score : 6 variables

6 variables: age, BMI, blood glucose, platelet count, albumin, and aspartate aminotransferase [AST] to alanine aminotransferase [ALT] ratio

The Fibrosis (FIB)-4 Score:

4 variables: age, AST, ALT, and platelet count

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Primary care treatment for NAFLD

Manage NAFLD in primary care if other causes of liver disease have been excluded, and there is a low risk of advanced liver fibrosis.

  1. Diet and lifestyle advice: avoiding excess alcohol, dietary modification, reduce calorie intake, increase physical activity, induce gradual and long-term weight loss

  2. Screen and treat diabetes, hypertension and hyperlipidaemia (statins)

  3. Assess QRISK 3

Secondary care management of NAFLD

  1. Assessment of liver disease

  2. Management of advanced fibrosis

  3. Screening and treatment of portal hypertension and oesophageal varices

  4. Hepatocellular carcinoma HCC surveillance and management (ultrasound scans and serum AFP alpha-fetoprotein monitoring)

Dr Rajesh VarmaNAFLD, non-alcoholic fatty liver disease