03-18 NAFLD

Question 1

OBJECTIVE: Define NAFLD

Answer 1

a spectrum of liver damage [resembling EtOH injury] ranging from simple steatosis to steatohepatitis (fatty liver plus inflam and/or necrosis), advanced fibrosis, and cirrhosis.
—differentiated from steatosis that results from 2° causes such as drug-induced steatosis

Question 2

OBJECTIVE: Discuss the epidemiology, risk factors, and prevalence of NAFLD

Answer 2

Epidemiology
—The majority of cases occur between the ages of 40 and 60; however it can occur in any age group including children.

Risk Factors
—Metabolic syndrome (abdominal obesity, hypertension, diabetes and dyslipidemia) –> don’t need all of ‘em
—some evidence that fatty liver pts, w/ metab syn are more likely to have NASH and/or fibrosis than simple steatosis

Prevalence
—0-24% of gen population
—57-74% in obese
—50% in diabetics

Question 3

OBJECTIVE: Discuss the pathogenesis of NAFLD

Answer 3

Inflammatory mediators are in excess of anti-inflammatory mediators in metabolic syndrome, particularly from VISCERAL fat
—Data show that for sure fatty acids, adiponectin and TNFα are all involved
—excess adipose tissue sends lots of FFAs to liver
—adiponectin normally 1) blocks hepatocytes uptake of FFAs, 2) stims FA oxidation/export and 3) ‪↓‬ insulin resistance
—But excess FFAs stimulate production of TNFα
—TNFα 1) inhibits adiponectin → ↑ hepatocyte FFA uptake and ↑ insulin resistance, 2) is a pro-apoptotic and 3) recruits WBCs
—hepatocytes try to rid themselves of all this fat and in so doing generate ROS’s; TNFα also ↑ ROS’s

Question 4

OBJECTIVE: Describe the histological features and spectrum of Non-alcoholic fatty liver disease and Non-alcoholic steatohepatitis (NAFLD/NASH)

Answer 4

Virtually same appearance as EtOH-liver:
—steatosis, mixed inflammatory cell infiltration (neutrophils and lymphocytes), hepatocyte ballooning and necrosis, glycogen nuclei, Mallory’s hyaline, and fibrosis.
—The presence of these features, alone or in combination, accounts for the wide spectrum of non alcoholic fatty liver disease.
—Portal tracts are relatively spared from inflammation.

Question 5

OBJECTIVE: Describe the natural history of NAFLD/NASH

Answer 5

Usually plain old NAFLD is completely reversible; only 3% → cirrhosis over 10 yrs
—NASH has a more variable course that depends on the point in dz progression at which you make dx
—30% of NASH pts → cirrhosis in 10yrs
—Risk factors for worse outcomes include: older, obesity and DM.

Question 6

OBJECTIVE: Describe the management of NAFLD/NASH

Answer 6

No exact tx guidelines here. generally:

SCREEN
—R/o other possible causes of liver dz
—screen for cirrhosis, HCC and portal HTN
—f/u w/ pts to screen for dz progression

UNIVERSAL TX RECOMMENDATIONS
—WEIGHT LOSS (not too fast, can → ↑ hepatic necro-inflammation); consider bariatric surgery
—DIET: low CARB, low calorie esp; avoid HFCS and trans-fat, coffee may be good
—EXERCISE
—DIABETES - get it under control
—STATINS - OK to use even w/ ↑ LFTs; follow LFTs, they should go down; statins may also ‪↓ risk of HCC‬)

CASE-BY-CASE TX
—Vit E: give to pts w/ full blown NASH who don’t have CVD (Vit E may increase cardio mortality risk)
—Metformin
—Pioglitazone and Rosiglitazone
—Betaine - normal component of metabolic cycle of methionine; has a protective effect against steatosis in animal models
—UCDA (Ursodeoxycholic acid ) - a natural hydrophilic bile acid

Question 7

S/Sx of NAFLD/NASH

Answer 7

Usually asx at first and just end up w/ high LFTs on routine blood worko; may report fullness in RUQ, general malaise/lethargy

Question 8

Lab findings in NAFLD/NASH

Answer 8

METAB STUDIES
LDL/HDL/TGs - Dyslipidemia
HgA1c > 6.5%
—Suggestive of metab syn

LIVER ENZYMES
AST- usually 3-5X
ALT- usually 3-5X
ALP- usually 2X
AST:ALT ratio- most cases 10X nl) consider DDx

IRON AND COPPER STUDIES
Ferritin- ↑ in 50% of patients
Transferrin sat- ↑ in 6-11% of patients
Hepatic iron index- almost always normal
Serum ceruloplasmin - wnl
Serum copper levels - wnl

VIRAL SERLOGIES
Negative for HAV, HBV, HEV

A1AT normal

OTHER STUDIES
—Hypoalbuminemia, prolonged PT hyperbilirubinemia may be found in patients with cirrhotic stage fatty liver disease.

Question 9

Imaging Findings in NAFLD/NASH

Answer 9

US fat produces a diffuse ↑echogenicity compared w/ kidneys; has 89% sensitivity of 89% and 93% specificity in detecting steatosis. CT and MRI can also diagnose fatty liver. No imaging study can differentiate simple steatosis from steatohepatitis.