NAFLD Flashcards
What is NAFLD and what are the different stages of NAFLD?
Fatty infiltrations and inflammation can lead to oxidative stress injury and lipid peroxidation which leads to fibrosis
- Steatosis (F0-1)
- fat in liver w/o inflammation or fibrosis - NASH (F2-3)
- non-alcoholic steatohepatitis
- would need liver biopsy to diagnose and identify the inflammation to differentiate from steatosis
- increasing fibrosis - NASH + Fibrosis (F3-4)
- cirrhosis
What is the pathophysiology underlying NAFLD? What conditions is it associated with?
STEATOSIS
Increased free fatty acids (FFA) from the diet, lipogenesis and lipolysis results in formation of triglycerides and formation of fat droplets which are deposited in the liver
INFLAMMATION + FIBROSIS
Impaired oxygenation of FFA leads to increased ROS
Stimulates inflammation -> induces steatohepatitis
Increased immune cells recruited and increased fibrosis over time
Associated with other metabolic disorders i.e. diabetes and obesity
What is the pathophysiological hallmark of NAFLD?
Insulin resistance contributes to NAFLD by:
- Increases the de novo lipogenesis
- increases FFA flux to liver via decreased inhibition of lipolysis
- stimulates connective tissue growth factor= increased fibrosis process
What are the histological signs of NAFLD?
Steatosis= white circles to show fat deposits
Fibrosis= thick pink bands -> bands of collagen i.e. fibrotic nodules
What are the risk factors associated with NAFLD?
Obesity Poor diet Low activity levels Type 2 diabetes High cholesterol Middle age Smoking HTN
NOTE: considered part of metabolic disorders
What investigations can be done to identify NAFLD?
LFTs:
-derranged -> might have increased AST/ALT ratio (present with increased fibrosis)
Enhanced Liver Fibrosis (ELF)
- 1st line method for investigation fibrosis
- <7.7= non to mild fibrosis
- > = 7.7-9.8= moderate fibrosis
- > =9.8= severe fibrosis
NAFLD fibrosis score
- 2nd line (when ELF not available)
- includes age/BMI/liver enzymes/platelets/albumin/diabetes
- RULE OUT fibrosis but not severity
Fibroscan:
- 3rd line
- US measuring the stiffness of liver to give indication of fibrosis
- use if ELF or NAFLD fibrosis scores indicate fibrosis
NOTE:
-if fibroscan was between 18-20 then would indicate advanced fibrosis/cirrhosis = indication for liver biopsy
What additional tests might you need to perform when LFTs are deranged to rule out other causes besides NAFLD?
Need to do investigations to rule out other causes of deranged LFTs i.e. NON-INVASIVE LIVER SCREEN
- Hep B and C serology
- Autoantibodies (ANA, SMA, AMA, LKM-1)
- Immunoglobulins (AI hepatitis)
- Caeruloplasmin (Wilsons disease)
- Alpha 1 anti-trypsin levels
- ferritin and transferrin sat (hereditary haemochromatosis)
- US of liver
What is the process of determining whether patient with suggestion of NAFLD (on US or in LFT when no other cause present) is high or low risk for advanced fibrosis?
How does the management change depending on the risk of advanced fibrosis?
NAFLD fibrosis + ELF score or Fibroscan generates number:
> 8 = high risk of liver fibrosis
- refer to hepatology clinic
- assessment of liver disease and advanced fibrosis
- screening and treatment of portal hypertension
- HCC screening and management
<8= low risk of liver fibrosis
- manage in primary care
- assess CVS risk
- QRISK3 (cholesterol score)-> indicates whether statins needed
- diabetes control
- HTN control
- life style advice i.e. weight loss and alcohol
Why is it important to start diabetic patients at risk of NAFLD + fibrosis on GLP-1 agonists and SGLT-2 inhibitors early?
Can help with weight loss-> can help to control risk factor
Can help to manage insulin resistance to help to prevent continued contribution to pathophysiology
What roles do vitamin E and pioglitazone have in managing patients with fibrosis in NAFLD?
Vitamin E:
-potential antioxidant= reduces oxidative stress in NAFLD which is one of the drivers of pathophysiology
Pioglitazone:
-targets insulin resistance and adipose tissue dysfunction (both drivers of NAFLD pathophysiology)
