Non-Alcoholic Fatty Liver Disease (NAFLD)

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1- Introduction, Definition & Overview

2- Pathophysiology

3- Risk Factors 

4-Epidemiology

5- Clinical Features

6- Investigations

7- Management

8- Prognosis

Introduction, Definition & Overview

NAFLD is a spectrum of liver diseases characterized by hepatic fat accumulation (>5%) in individuals without significant alcohol consumption.
It ranges from:

  • Simple steatosis (fat only)

  • To non-alcoholic steatohepatitis (NASH) → inflammation ± ballooning ± fibrosis

  • Eventually leading to cirrhosis and hepatocellular carcinoma (HCC)

 

It’s considered the hepatic manifestation of metabolic syndrome.

© image from Wikimedia Commons

Pathophysiology

NAFLD pathogenesis involves:

 

  • First hit: Insulin resistance → ↑ hepatic free fatty acids → steatosis

  • Second hits (progression to NASH/fibrosis):

    • Oxidative stress (free radicals)

    • Lipotoxicity

    • Cytokine release (e.g. TNF-α)

    • Gut-derived endotoxins

    • Endoplasmic reticulum stress

    • Genetic predisposition (e.g. PNPLA3)

Risk Factors

  • Obesity (especially central)

  • Type 2 diabetes

  • Dyslipidaemia

  • Hypertension

  • Polycystic ovary syndrome

  • Obstructive sleep apnoea

  • Sedentary lifestyle

Epidemiology

  • Affects ~24% globally

  • Present in:

    • 94% of obese (BMI >30)

    • 67% of overweight (BMI >25)

    • 25% of normal BMI

  • Strong ethnic & gender variations

Clinical Features

  • Often asymptomatic

  • May cause fatigue, mild RUQ discomfort

  • Detected incidentally via:

    • Elevated liver enzymes (ALT > AST early on)

    • ‘Bright liver’ on ultrasound

 

  • May present late with:

    • Cirrhosis (ascites, varices, encephalopathy)

    • Hepatocellular carcinoma

Investigations

  • Aim: Confirm steatosis, assess fibrosis, exclude other liver diseases

    -Biochemistry

    • ↑ GGT common

    • ALT/AST mildly raised

    • AST:ALT ratio inverts with advanced fibrosis

    • Ferritin may be elevated

    • ANA may be low-titre positive

    -Fibrosis scores

    • NAFLD Fibrosis Score, FIB-4 → rule out advanced fibrosis

    • Enhanced Liver Fibrosis (ELF) panel (specialist use)

    -Imaging

    • Ultrasound (low sensitivity <33% steatosis)

    • Transient Elastography (for fibrosis)

    • CAP (for fat content)

    –Liver biopsy

    • Not routinely required

    • “Gold standard” for diagnosing NASH and assessing fibrosis

Management

Lifestyle is the cornerstone:

  • Weight loss (≥7–10%) improves steatosis and inflammation

  • Control of diabetes, dyslipidaemia, and hypertension

  • Avoid hepatotoxic drugs & alcohol

-Surveillance

  • HCC screening in cirrhotic patients

  • Cardiovascular risk assessment (leading cause of death)

-Referral

  • Patients with advanced fibrosis (FIB-4 >2.67 or TE >8kPa) should be referred to hepatology

Prognosis

  • Fibrosis stage is the key determinant of prognosis

  • Simple steatosis → benign

  • NASH with fibrosis → progressive disease

  • High risk of:

    • Liver-related events (cirrhosis, HCC)

    • Extrahepatic events (CV disease, cancer)

NAFLD is projected to become the leading indication for liver transplantation globally

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