1. Non Alcoholic Fatty Liver dis.

2. Non alcoholic fatty liver dis.
accumulation of macro vesicular fat in hepatocytes up to 40% of liver weight.
Terminology:
hepatic steatosis in obese adults half century ago
Findings in liver histology
similar to Alcoholic liver dis.
( NAFLD )
NASH

3. Hepatic steatosis: Primary: Obesity - ins resistance
Secondary : drugs – Toxin
metabolic – etc.
Epidemiology:
FL in 2/6% school age children in Japan.
FL in 9% of autopsies in 2-19 yrs old.

4. Pathophysiology:
In fed state ins and parasympatic system lipid accumulation in liver and adipose tissue
In fasting glucagon and sympatic system FFA as brain and muscle fuel.
Starvation
TPN DM
steroids
FFA, but not oxidation in liver steatosis

5. Obesity DM hyperlipemia
Insulin resistance
FFA in liver
Steatosis
NAFLD
Oxidative stress
Lipid peroxidation
Genetic
glutatione
ATP
Inflam. Cytokines
Inflam Necrosis fibrosis
NASH

6. Ins resistance glucose transport and. metabolism in adipocytes
Ins resistance glucose transport and metabolism in adipocytes and skeletal muscle
lipolysis circulating FFA
8-10% of NAFLD have DM

7. Diagnosis:
usually asymptomatic
ALT
90% NAFLD children are obese
acanthosis nigricans in 30-50%
vague abd. pain in 30%
hepatomegaly in 40-50%

8. DD: infection : HCV
immunologic : AIH
celiac
IBD
DM 1
medication : Amiodarone
glucocorticoids
antiretroviral
tetracyclin
L- Asparginase
colchicin
valproic acid

9. Metabolic : abetalipoproteinemia
α1 AT Def.
galactosemia
tyrosinemia
fruct. Int.
GSD TG
Reye
homocystinuria
wilson
mitochondrial dis.

10. Nutritional : PEM
EFA
starvation
obesity
jejunoileal bypass
TPN
Toxins: ethanol

11. Pathology:
for 1) definitive diagnosis of NAFLD ) discrimination of NASH from milder forms of FL
3) diagnosis of other cases like AIH
4)in adults with suspected NAFLD
DM age>40yrs

14. NAFLD:
Macrovesicular steatosis
Perisinosoidal fibrosis
Balloon degeneration
Lobular inflammation
Mallory hyaline
Megamitochondria
Brunt criteria: steatosis (0-3)
lobular inflammation (0-3)
ballooning (0-2)
NASH

16. Progression rate to cirrhosis is unknown
NASH induced CLD are suseptible to HCC.
Advanced fibrosis is present at the time of diagnosis in 5-10% of children with NAFLD

18. ALT > 1/ GGT - TG
NL FBS - fasting insulin - TNFα- Adiponectin

19. The minimum warkup : FBS
insuline
lipids
TFT?

20. Imaging : sonography when the liver fat is >30% CT without contrast
MRI ( Ideal )

21. Treatment : control of weight
change in life style diet exercise
taurine
Vit E
ursobil
metformin

26. Metabolic Syndrome (Syndrome X)
3 or more of the following:
1.Abdominal obesity (waist > 40” for men and 34.5” for women)
2.Triglyceride level >150 mg/dL
3.HDL <40 mg/dL for men and <50 mg/dL for women
4.Fasting blood glucose 110 mg/dL
5.Blood pressure 130/85
Slide 60
Metabolic Syndrome (Syndrome X)
Syndrome X - that’s the insulin resistant syndrome - is estimated to affect almost 47 million Americans. Diagnosis is based on having three or more of the following characteristics: abdominal obesity, high triglycerides, low HDL, elevated fasting sugar or hypertension. If you have three or more of those you clinically can be diagnosed as having Syndrome X.

27. Spectrum of Hepatic Pathology Hepatocellular carcinoma
NAFLD
Spectrum of Hepatic Pathology
Steatohepatitis
Steatosis
Slide 59
NAFLD: Spectrum of Hepatic Pathology
The next several slides illustrate the histopathology of NAFLD. As mentioned earlier, nonalcoholic fatty liver disease (NAFLD) is a spectrum of hepatic pathology that ranges from fatty liver (steatosis) on the most clinically-benign end of the spectrum to cirrhosis on the opposite extreme where most liver-related morbidity and mortality occur. Nonalcoholic steatohepatitis (NASH) is an intermediate form of liver damage that sometimes progresses to cirrhosis. Some individuals who become cirrhotic from NAFLD develop hepatocellular carcinoma.
Brunt EM. Nonalcoholic steatohepatitis. Semin Liver Dis 2004;24:3-20.
Cirrhosis
Hepatocellular carcinoma