What are the dangers of Non-Alcoholic Fatty Liver Disease (NAFLD)?

Dangers of Non-Alcoholic Fatty Liver Disease (NAFLD)

Non-Alcoholic Fatty Liver Disease (NAFLD) poses significant dangers including increased cardiovascular mortality, progression to cirrhosis, liver failure, and hepatocellular carcinoma, with cardiovascular disease being the leading cause of death in these patients. 1

Disease Spectrum and Progression

NAFLD encompasses a spectrum of liver conditions in individuals without significant alcohol consumption:

• Non-alcoholic Fatty Liver (NAFL): Hepatic steatosis without evidence of hepatocellular injury

  • Minimal risk of progression to cirrhosis and liver failure 1

• Non-alcoholic Steatohepatitis (NASH): Hepatic steatosis with inflammation and hepatocyte injury

  • Can progress to cirrhosis, liver failure, and hepatocellular carcinoma
  • Associated with increased liver-related mortality 1

• NASH Cirrhosis: Cirrhosis with current or previous evidence of steatosis or steatohepatitis 1

The disease progression rate corresponds to:

• 1 fibrosis stage every 14 years in NAFL
• 1 fibrosis stage every 7 years in NASH
• Progression rate doubles with arterial hypertension 1

Major Health Risks

1. Cardiovascular Disease

• Leading cause of death in NAFLD patients 1
• Higher prevalence and incidence of CVD in NAFLD than matched controls 1
• Associated with:
  • Pre-atherogenic lesions (increased carotid intima-media thickness)
  • Coronary artery calcifications
  • Endothelial dysfunction
  • Altered cardiac energy metabolism 1
• Risk increases further in NASH and advanced fibrosis 1

2. Liver-Related Complications

• Cirrhosis and End-Stage Liver Disease

  • Patients with NASH (not NAFL) have increased liver-related mortality 1
  • Risk of decompensated liver disease (jaundice, ascites, hepatic encephalopathy, variceal bleeding) 1
  • May require liver transplantation 1

• Hepatocellular Carcinoma (HCC)

  • Increased risk in NAFLD, particularly with advanced fibrosis and cirrhosis 1
  • Can occur even in the absence of cirrhosis 1, 2

3. Metabolic Complications

• Type 2 Diabetes

  • Bidirectional relationship: NAFLD both increases risk and worsens diabetes 3
  • NAFLD prevalence in diabetic patients is 60-75% 1

• Chronic Kidney Disease

  • NAFLD contributes to pathophysiology and progression 2, 3

4. Other Associated Conditions

• Extrahepatic Malignancies

  • Increased risk of colorectal polyps and cancer 1, 3
  • Association with various other extrahepatic malignancies 3

• Other Conditions:

  • Osteoporosis
  • Obstructive sleep apnea
  • Polycystic ovary syndrome
  • Stroke 3

Risk Factors for NAFLD

Major risk factors include:

• Obesity
• Type 2 diabetes
• Dyslipidemia
• Metabolic syndrome 1

Additional risk factors:

• Hypothyroidism
• Obstructive sleep apnea
• Hypopituitarism
• Hypogonadism
• Polycystic ovary syndrome 1

Mortality Risk

• Overall mortality is increased compared to matched control populations 1
• Main causes of death:
  1. Cardiovascular disease (predominant cause)
  2. Malignant tumors
  3. Liver diseases 1

Clinical Implications

• Patients with NASH and fibrosis require closer monitoring (annually) 1
• Patients with NASH cirrhosis should be monitored at 6-month intervals 1
• Cardiovascular risk assessment is mandatory in all NAFLD patients 1
• Statin therapy should not be withheld from NAFLD patients, including those with compensated cirrhosis, as benefits significantly outweigh risks 1
• Patients with decompensated liver disease caused by NAFLD should be considered for liver transplantation 1

Emerging Terminology

The American Diabetes Association now recommends using the terms:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) instead of NAFLD
• Metabolic dysfunction-associated steatohepatitis (MASH) instead of NASH 4

This change aims to address stigma, provide a positive diagnosis approach, and reflect pathophysiological accuracy.