( NASH)
Nomenclature
Alcoholic fatty liver disease
Alcoholic fatty liver
Alcoholic steatohepatitis (ASH)
Non-alcoholic fatty liver disease (NAFLD)
Non-alcoholic fatty liver
Non-alcoholic steatohepatitis
Norm Liver
NAFLD
NASH
Second hit
Fat metabolism
Dietary fat
hepatocyte
Triglyceride
Chylomicrons
Apoprotein
chylomicron
remnants
Lipolysis
AT
VLDL
non-esterified
fatty acids
fatty acids
triglycerides
Fatty acids
Second hit
Hepatic fibrogenesis
Early phase
Fas receptors
Accumulation of ROS
Release of proinflamatory
cytokine
Release of anti inflamatory
cytokine
Hepatocellular
damage
immunocytes
Hepatic fibrogenesis
Later phase
Inflamatory cells
inflitration
Growth factor
TGF beta,leptin,angiotensin II
Activated HCs
Profibrogenic cytokine
Collagenase
Increase collagen synthesis
Decrease collagen removal
Risk factors
Metabolic condition
Obesity
DM
Hyperlipidemia
Rapid weigth loss
TPN
Surgical procedure
Small bowel resection, bypass
Other conditions
Bacterial overgrowth
Drugs
Obesity
Obesity most often associated with NAFLD
1151 obese patients :
-
Diabetes mellitus
At the time of diagnosis of NASH up to 33% of patients
have type 2 DM
Prevalence of NASH was higher among ODM than ONDM
DM and impaired glucose tolerance are strong independent
predictor of severe hepatic fibrosis in NASH
DM and impaired glucose tolerance have sevenfold
increase risk of fibrosis.
( Marcau et al 1999 )
Insulin resistence
Severity of steatosis positively correlated with
- BMI
- plasma triglyceride
- Fasting plasma glucose
- plasma insulin
Metabolic syndrome was an independent predictor of
NASH
Among 90 NASH patients, 85% have metabolic
syndrome at time of diagnosis.
( Scheen AJ 2002)
Natural history
Non-alcoholic
Obesitas, DM, drugs
NAFLD ( 80%)
NASH ( 20%)
Alcoholic
Daily alcohol
consumption > 30 g.
AFLD ( 45% )
ASH ( 85% )
Diagnosis
Laboratory parameter
Serum transaminase increase
Ratio AST/ALT usualy < 1
Ratio AST/ALT > 1 : severe or late condition
GGT and AP normal or slightly increase
Transferin saturation and feritin increase in
60% cases
If CH present, laboratory parameter is similar
with CH of other causes
Diagnosis
Clinical picture of NASH is similar with all other
chronic liver disease, uncharacteristic
Bright liver on USG, only in early stage
By exclusion :
- Alcohol consumption
- Serologic marker for viral hepatitis
- Serologic marker for autoimmune hepatitis
- Marker for hemochromatosis
Diagnosis
Histopatologic findings in NASH
- Vesicular fatty degeneration
- Lobular hepatitis
- Balloning, focal and individual cell necrosis
- Mallory bodies, apoptosis
- Mixed cell periportal infiltration
- Pericelular net work fibrosis
- central to central and periportal to periportal
fibrotic strand
- Complete cirrhosis
Therapy
Therapy
Body weight reduction
Slowly but sure
Reduction of BW about 10% is
beneficial in improving lab parameter
The best treatment is a low calorie diet
for rest of life
Therapy
Diabetes mellitus (with obesity)
Drugs improving insulin sensitivity
- Metformin
- Troglitazone
Therapy
Ursodeoxycholic acid
Displaces the more hydrophobic bile acids
Cytoprotective
Immunomodulator
Antiapoptotic
Reduced the incidence of bacterial overgrowth
Beware,