Clin Med - NAFLD Flashcards
What is non-alcoholic fatty liver disease (NAFLD)?
- Often called “Fatty Liver”
- The hepatic manifestation of metabolic syndrome
- Although initially benign, it can slowly progress to hepatitis and even cirrhosis
Where are the lipids deposited in the liver?
Into the hepatocytes
-it takes up space and the cells can’t function properly, signals inflammatory response
How will fatty liver appear on ultrasound?
Increased echogenicity - pale and dense
Fibrosis and mortality
The more fibrosis, the worse the prognosis.
*Fibrosis is an early indication of which patients with fatty liver will have the most difficult disease progression.
Progression of Fatty Change
- simple liver steatosis
- non-alcoholic steatohepatitis (NASH)
- non-alcoholic steatohepatitis with fibrosis
- cirrhosis
Gross morphology of NAFLD
Soft, yellow, greasy, often enlarged
Define simple fatty liver
i. e. “hepatis steatosis”
- Fat accumulation in hepatocytes
- 70% of NAFLD
Define non-alcoholic hepatosteatosis
i. e. “NASH”
- Fat + inflammation, causes cell injury, a hepatitis, can elevate liver enzymes
- 30% of NAFLD
Define fibrosis
- Scarring in liver tissue
- NASH + fibrosis = very predictive progression to ESLD
Define cirrhosis
- scar –> nodules
- irreversible damage likely to progress to ESLD
Epidemiology of NAFLD
- most common form of chronic liver disease in the Western world
- parallels the obesity epidemic
Population prevalence of NAFLD
- Highest in Hispanics, followed by non-Hispanic caucasians
- Lowest in non-Hispanic blacks
Future predictions
in 20 years, NASH will be the #1 cause for liver transplant (surpassing both chronic hepatitis C and alcoholic cirrhosis)
Pathogenesis - hepatic lipogenesis leading to hepatic steatosis
- insulin resistance –> lipolysis –> increased plasma free fatty acids –> inappropriately shifted to the liver
- de novo hepatic synthesis of fat, genetics
- accumulation of triglyceride as lipid droplets in cytoplasm of hepatocytes
“Multiple hit theory”
1st Hit: hepatic steatosis (insulin shifts)
2nd Hit: oxidative stress due to free radical formation, cardiolipin peroxidation, cytokines, apoptosis, and gut-derived bacterial endotoxinemia
3rd Hit: gene involvement (PNPLA3), impaired hepatocyte regeneration
Risk Factors of NAFLD
- OBESITY with or without: metabolic syndrome, insulin resistance, and/or type II DM
- hypothyroidism, sleep apnea, PCO, past surgeries, meds, parenteral nutrition
Diff Dx for NAFLD
- Alcoholic Hepatitis
- Hepatitis C
- Medications
- Parenteral nutrition
- Wilson’s disease
- Severe malnutrition
- Hemochromatosis
- Autoimmune liver disease
- Alpha-1 antitrypsin deficiency
Is NAFLD diagnosed on clinical presentation?
NO! Most patients are asymptomatic
- might c/o weight gain
- mild elevated of liver enzymes
- maybe RUQ discomfort
- PMH of insulin resistance or metabolic syndrome
- dx requires NO history of “heavy” alcohol consumption
What is “heavy” alcohol use?
Men: > 4 drinks per day or > 14 drinks per week
Women: > 3 drinks per day or > 7 drinks per week
A standard alcoholic drink is:
- 12 oz beer
- 5 oz wine
- 1.5 oz liquor
NAFLD - physical exam
- Obesity
- +/- Hepatomegaly
- Mild RUQ tenderness, negative Murphy’s Sign
- Stigmata of liver disease or cirrhosis (rarely would present with these)
- palmar erythema, spider nevi, caput medusa, telangiectasia, ascites, edema, jaundice, mental fog or confusion
NAFLD liver enzymes tests
NAFLD is most common cause of incidental abnormal LFTs in western world!!!
Do you see AST or ALT most predictive of fatty liver?
ALT
When AST > ALT you think…
the patient is consuming alcohol
Upper range of normal for AST, ALT, Alk Phos
AST - aspartate aminotransferase 10 – 40 IU/L
ALT - alanine aminotransferase 7 – 56 IU/L
Alkaline Phosphatase 44-147 IU/L
