Non Alcoholic Fatty Liver Disease (NAFLD) 

1. Definition & Terminology 

NAFLD = hepatic steatosis (≥5% hepatocytes with fat) without significant alcohol intake and no other secondary cause.

Alcohol threshold (MRCP)

• Men: <30 g/day
• Women: <20 g/day

2. New Nomenclature 

In 2023, international consensus replaced NAFLD terminology:

3. Epidemiology 

• Prevalence: ~25–30% worldwide
• Most common liver disease globally
• Increasing with obesity and diabetes epidemic
• Leading cause of liver transplantation in West

High risk groups:

• Type 2 DM (50–70%)
• Obesity (60–90%)
• Metabolic syndrome

4. Pathogenesis – “Multiple Hit Hypothesis”

Key mechanisms:

1. Insulin resistance → ↑ lipolysis → ↑ free fatty acids
2. Hepatic fat accumulation
3. Oxidative stress
4. Mitochondrial dysfunction
5. Cytokine-mediated inflammation
6. Fibrosis progression

5. Spectrum of Disease 

6. Risk Factors 

• Central obesity
• Type 2 diabetes
• Dyslipidaemia
• Hypertension
• PCOS
• OSA
• Hypothyroidism

Drugs:

• Amiodarone
• Methotrexate
• Tamoxifen
• Steroids

7. Clinical Features

Most patients:

• Asymptomatic
• Incidental LFT abnormality

Possible findings:

• Fatigue
• Right upper quadrant discomfort
• Hepatomegaly

Advanced disease:

• Portal hypertension signs
• Ascites
• Varices

 LFT Pattern 

• Mild ALT elevation (ALT > AST early)
• AST/ALT ratio <1
• GGT mildly elevated
• ALP normal or mildly raised
• Bilirubin normal until advanced

 When cirrhosis develops → AST > ALT

8. Investigations

A. Ultrasound (First-line)

Findings:

• Bright liver
• Increased echogenicity
• Poor visualization of portal veins

Limitation:

• Detects steatosis only if >20–30%

B. Transient Elastography (FibroScan)

• Measures liver stiffness
• CAP score measures fat
• Used to assess fibrosis

C. Non-invasive Fibrosis Scores 

FIB-4 Score

Uses:

• Age
• AST
• ALT
• Platelets

Interpretation:

• <1.3 → Low risk
• 1.3–2.67 → Indeterminate
• 2.67 → High risk fibrosis
  

NAFLD Fibrosis Score

Includes:

• Age
• BMI
• Glucose
• AST/ALT
• Platelets
• Albumin

D. Liver Biopsy (Gold Standard)

Indications:

• Diagnostic uncertainty
• Suspected advanced fibrosis
• Before clinical trials

Histology:

• Macrovesicular steatosis
• Ballooning degeneration
• Mallory-Denk bodies
• Lobular inflammation

9. Diagnosis 

Diagnosis requires:

1. Evidence of steatosis
2. Exclusion of:
• Alcohol excess
• Viral hepatitis
• Autoimmune hepatitis
• Wilson’s
• Hemochromatosis
• Drug causes

10. Management – Guideline Based (NICE + EASL)

A. Lifestyle Modification (Cornerstone)

Target weight loss:

• 5% → improves steatosis
• 7–10% → improves NASH
• 10% → improves fibrosis

Diet:

• Mediterranean diet(plant-based dietary pattern)
• Reduce fructose
• Avoid sugary drinks

Exercise:

• 150–300 min/week moderate intensity

B. Pharmacological Therapy (Only in selected cases)

Pioglitazone

• For biopsy-proven NASH (especially diabetics)

Vitamin E (800 IU/day)

• Non-diabetic biopsy-proven NASH

GLP-1 agonists (e.g., Semaglutide)

• Weight loss benefit
• Promising evidence

SGLT2 inhibitors

• Benefit in T2DM patients

C. Bariatric Surgery

• BMI >35 with comorbidities
• Improves histology

11. Complications

• Cirrhosis
• Portal hypertension
• HCC (even without cirrhosis)
• Cardiovascular disease (leading cause of death!)

12. Surveillance

If cirrhosis:

• 6-monthly ultrasound for HCC
• Variceal screening

If advanced fibrosis:

• Specialist referral

13. Cardiovascular Risk 

Most common cause of death:
➡️ Cardiovascular disease

Hence:

• Aggressive risk factor control
• Statins are SAFE in NAFLD

14. Special Situations

Lean NAFLD

• Normal BMI
• More common in Asians
• Associated with visceral fat

NAFLD in Diabetes

• Screen with FIB-4
• High risk of fibrosis