Nonalcoholic fatty liver disease Flashcards
define Non-alcoholic fatty liver disease
how much ethanol consumption in diagnsosis?
what type of hepatic steatosis?
An acquired liver disease in children and adults
Increased with the epidemic of obesity in the United States
Macrovesicular hepatic steatosis
Ethanol < 20 gm per day
what two conditions under nonalcoholic liver disease?
Steatosis
Non-Alcoholic Steatohepatitis (NASH)
what is the epidemiology of NASH
how many adults; kids? by 2025?
NAFLD: 20-30% of adults, 10% of children
By 2025, over 25 million Americans are predicted to have NASH related liver disease
The next epidemic for liver disease
fatty liver:
how many normal individuals?
obese individulals?
NASH:
how many normal?
obese?
Fatty Liver:
10-15% of normal individuals
70-80% of obese
NASH:
3% of normal
15-20% of morbidly obese (BMI > 35)
conditions associated with NAFLD (4)
how about race?gender? family?
Obesity
Type 2 Diabetes
Hyperlipidemia
Metabolic Syndrome
Race/Ethnicity
Mexican Americans have the highest
African Americans lowest
Gender
Initially 53-85% women
More recent studies 50:50
Familial component
? Dietary habits, genetics
what is the leading cause of pediatric liver disease?
10% of children have NAFLD
NAFLD: leading cause of Pediatric liver disease
130 patients with NAFLD with liver biopsy:
median age 12
87% had fibrosis, 20% had bridging fibrosis
In 100 children with NASH, 8% had advanced fibrosis and 3% had cirrhosis
what nutritional abnormalities lead to NAFLD(2) ? metabolic diseases? (2)
Nutritional Abnormalities
Total Parenteral Nutrition
Starvation, Refeeding
Metabolic Diseases
Abetalipoproteinemia
Hypobetalipoproteinemia
which chemical exposures lead to NAFLD?
Occupational Chemical Exposure
Drugs
Tamoxifen
Corticosteroids
Amiodarone
Methotrexate
Anti-retroviral therapy
which types of surgeries cause NAFLD?
Surgery – with rapid, excessive wt loss
Jejunoileal bypass
Gastric bypass – less common
natural history of fatty liver?
natural history of NASH?
What does NASH induce? what is it an increasing cause of?
Fatty Liver: limited progression
NASH: 30-40% with advanced fibrosis
10-15% with cirrhosis
NASH induced cirrhosis is an increasing cause of Hepatocellular Carcinoma
what is steatosis a result of?
Steatosis: a result of disturbed balance
More lipogenesis/ increased FFA
normally:
Normally triglycerides incorporated into chylomicrons
Travel via lymphatics to peripheral fat
Hydrolyzed to free fatty acids
Stored in the liver
Oxidized by mitochondria
triglyceride/ cholesterol formation
pathogenesis
insulin resistance:
insulin on glucose uptake? lipolysis? mitochondrial FA oxidation?
Insulin resistance
Insulin promotes the uptake of glucose
Stored as glycogen
Inhibits lipolysis
Increased levels of insulin lead to increased lipogenesis, increased FFA
Increased mitochondrial fatty acid oxidation
Free radical formation and damage
obesity and pathogenesis of NAFLD:
Obesity
Increase in Synthesis of Free Fatty Acids (FFA)
Decrease in oxidation of FFA
Insulin Resistance
Increase in adipose tissue lipolysis
Increased FFA
in NAFLD pathogeneisis what do increased FFA lead to? (2)
- *Increase FFA leads to:**
1. Fatty Liver
2. Increased Oxidative Stress
2a. Increased Free Radicals
2b. Direct liver Injury
what is the two hit pathogeneisis hypothesis of NAFLD?
- *1. Hepatic fat accumulation**
- *2. Oxidative Stress via lipid peroxidation and free radicals**
know this
what are four diseases that can combine with NASH for concomitant liver disease?
Hepatitis C + NASH
Hemochromatosis + NASH
Alpha 1 Antitrypsin Deficiency + NASH
Alcohol + NASH
what are the clinical symptoms and signs of NAFLD
Most have no symptoms or signs of Chronic liver disease
Nonspecific symptoms: fatigue
what is on the physical exam of a NAFLD patient? (4)
Obesity – 30-100% of patients
Hepatomegaly – up to 50%
Spider angiomata
Palmer erythema
typical labs of NASH
Liver enzymes?
ALK phos?
In patients with NASH:
50-90% with elevated liver enzymes
AST and ALT: moderately elevated (up to 4 times normal)
Unlike Alcohol, AST is rare 2x ALT
Alkaline Phosphotase: up to 2 times normal
what does NASH liver look like on US?
US: homogeneously fatty infiltrated liver, increased echogenicity throughout
A “fatty” appearance on Ultrasound or CT does not make a ___________
A “fatty” appearance on Ultrasound or CT does not make a diagnosis
how would you distinguis between steatotis and steatohepatitis?
BIOPSY!!!!
Helps to exclude other causes
Liver biopsy is the only definitive way to diagnose NASH
Helps to stage the disease
define steatosis
Macrovesicular fat
define steatohepatitis( 4 things)
BHIM
Inflammation, Hepatocyte degeneration, Ballooning and Mallory Bodies
define fibrosis in NASH
when will cirrhosis occur?
Pericellular then Bridging
cirrhosis: 20% of patients in 10 years
what is the histology of NASH?
Predominately Macrovesicular steatosis
Mallory Hyaline Hepatocyte ballooning
Perivenular and
perisinusoidal fibrosis
“Chicken wire appearance”
how do you treat NASH(non-surgical)?
4
- WEIGHT reduction . weight reduction of 10% helpful
- if diabetic, optimize control
- if hyperlipidemic- treat this b/c of increased cardiac risk
- going herbal: coffee, 2 cups/day
bariatic surgery helps NASH pts with BMI > than?
what does gastric banding improve?
Bariatric surgery may help people with NASH whose BMI is >35
Gastric banding associated with improvement in inflammation and even fibrosis
what type of cirrhosis is caused by NASH?
Hepatitis C + NASH are increasing causes of ______\_and _______
NASH is felt to be a major cause of cryptogenic cirrhosis
Hepatitis C + NASH are increasing causes of cirrhosis and HCC
t/fNASH may worsen the course of other liver diseases
true
t/f
NASH has an increasing role as a cause of cirrhosis, HCC and liver transplantation
true
