Non Alcoholic Fatty Liver dis.. Non alcoholic fatty liver dis. accumulation of macro vesicular fat in hepatocytes up to 40% of liver weight. Terminology:

Non Alcoholic Fatty Non Alcoholic Fatty Liver dis. Liver dis.

Non alcoholic fatty liver dis. Non alcoholic fatty liver dis.

accumulation of macro vesicular fat in hepatocytes up to 40% of liver weight.

TerminologyTerminology:: hepatic steatosis in obese adults half century ago

Findings in liver histology 1979 similar to Alcoholic liver dis. ( NAFLD ) NASH 1980

accumulation of macro vesicular fat in hepatocytes up to 40% of liver weight.

TerminologyTerminology:: hepatic steatosis in obese adults half century ago

Findings in liver histology 1979 similar to Alcoholic liver dis. ( NAFLD ) NASH 1980

Hepatic steatosis: Primary: Obesity - ins resistance

Secondary : drugs – Toxin

metabolic – etc.

Epidemiology:Epidemiology:

FL in 2/6% school age children in Japan.

FL in 9% of autopsies in 2-19 yrs old.

Hepatic steatosis: Primary: Obesity - ins resistance

Secondary : drugs – Toxin

metabolic – etc.

Epidemiology:Epidemiology:

FL in 2/6% school age children in Japan.

FL in 9% of autopsies in 2-19 yrs old.

Pathophysiology:Pathophysiology:In fed state ins and parasympatic system In fed state ins and parasympatic system

lipid accumulation in liver and adipose tissue lipid accumulation in liver and adipose tissue In fasting glucagon and sympatic system In fasting glucagon and sympatic system

FFA as brain and muscle fuel.FFA as brain and muscle fuel.StarvationStarvationTPNTPNDMDMsteroids steroids

FFA, but not oxidation in liver steatosis

Obesity DMhyperlipemia

Obesity DMhyperlipemia

Insulin resistance Insulin resistance

NAFLDNAFLDFFA in liver Steatosis FFA in liver Steatosis

Genetic glutatione ATP

Genetic glutatione ATP

Oxidative stress

Lipid peroxidation

Oxidative stress

Lipid peroxidation

NASHNASH Inflam. Cytokines

Inflam. Necrosis

fibrosis

Inflam. Cytokines

Inflam. Necrosis

fibrosis

8-10% of NAFLD have DM

Ins resistanceIns resistance glucose transport and glucose transport and metabolism in metabolism in

adipocytes adipocytes and skeletal and skeletal muscle muscle

lipolysis circulating FFA lipolysis circulating FFA

DiagnosisDiagnosis::

usually asymptomatic usually asymptomatic

ALTALT

90% NAFLD children are obese90% NAFLD children are obese

acanthosis nigricans in 30-50%acanthosis nigricans in 30-50%

vague abd. pain in 30%vague abd. pain in 30%

hepatomegaly in 40-50% hepatomegaly in 40-50%

DiagnosisDiagnosis::

usually asymptomatic usually asymptomatic

ALTALT

90% NAFLD children are obese90% NAFLD children are obese

acanthosis nigricans in 30-50%acanthosis nigricans in 30-50%

vague abd. pain in 30%vague abd. pain in 30%

hepatomegaly in 40-50% hepatomegaly in 40-50%

DD:DD: infection : HCV infection : HCV immunologic : AIHimmunologic : AIH celiac celiac IBDIBD DM 1DM 1 medication : Amiodarone medication : Amiodarone glucocorticoidsglucocorticoids antiretroviral antiretroviral tetracyclin tetracyclin L- Asparginase L- Asparginase colchicincolchicin valproic acid valproic acid

DD:DD: infection : HCV infection : HCV immunologic : AIHimmunologic : AIH celiac celiac IBDIBD DM 1DM 1 medication : Amiodarone medication : Amiodarone glucocorticoidsglucocorticoids antiretroviral antiretroviral tetracyclin tetracyclin L- Asparginase L- Asparginase colchicincolchicin valproic acid valproic acid

Metabolic :Metabolic : abetalipoproteinemia abetalipoproteinemia αα11 AT Def. AT Def. galactosemia galactosemia tyrosinemia tyrosinemia fruct. Int. fruct. Int. GSDGSD TGTG Reye Reye homocystinuria homocystinuria wilson wilson mitochondrial dis.mitochondrial dis.

NutritionalNutritional : PEM : PEM

EFAEFA

starvation starvation

obesity obesity

jejunoileal bypass jejunoileal bypass

TPNTPN

Toxins: ethanol Toxins: ethanol

NutritionalNutritional : PEM : PEM

EFAEFA

starvation starvation

obesity obesity

jejunoileal bypass jejunoileal bypass

TPNTPN

Toxins: ethanol Toxins: ethanol

Pathology:Pathology:

for 1) definitive diagnosis of NAFLD for 1) definitive diagnosis of NAFLD 2) discrimination of 2) discrimination of NASH from NASH from milder milder forms of FLforms of FL

3) diagnosis of other cases like AIH 3) diagnosis of other cases like AIH

4)in adults with suspected NAFLD 4)in adults with suspected NAFLD

DMDM2 2 age>40yrsage>40yrs

Pathology:Pathology:

for 1) definitive diagnosis of NAFLD for 1) definitive diagnosis of NAFLD 2) discrimination of 2) discrimination of NASH from NASH from milder milder forms of FLforms of FL

3) diagnosis of other cases like AIH 3) diagnosis of other cases like AIH

4)in adults with suspected NAFLD 4)in adults with suspected NAFLD

DMDM2 2 age>40yrsage>40yrs

NAFLD:NAFLD:

Macrovesicular steatosisMacrovesicular steatosis

Perisinosoidal fibrosis Perisinosoidal fibrosis

Balloon degeneration Balloon degeneration

Lobular inflammation Lobular inflammation

Mallory hyaline Mallory hyaline

Megamitochondria Megamitochondria

Brunt criteriaBrunt criteria:: steatosis (0-3) steatosis (0-3)

lobular inflammation (0-3) lobular inflammation (0-3)

ballooning (0-2)ballooning (0-2)

NASHNASH

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

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

ALT - > 1/7 - GGT - TG ALT - > 1/7 - GGT - TG

NL FBS - fasting insulin - TNFNL FBS - fasting insulin - TNFαα- -

Adiponectin Adiponectin

ALT - > 1/7 - GGT - TG ALT - > 1/7 - GGT - TG

NL FBS - fasting insulin - TNFNL FBS - fasting insulin - TNFαα- -

Adiponectin Adiponectin

AST

ALT

The minimum warkupThe minimum warkup : FBS : FBS

insuline insuline

lipids lipids

TFT?TFT?

ImagingImaging : sonography when the liver : sonography when the liver fat is >30% fat is >30%

CT without contrast CT without contrast

MRI ( Ideal ) MRI ( Ideal )

Treatment :Treatment : control of weight control of weight

change in life style diet change in life style diet

exercise exercise

taurinetaurine

Vit E Vit E

ursobil ursobil

metformin metformin

Metabolic Syndrome(Syndrome X)

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 <50mg/dL for women

4. Fasting blood glucosemg/dL 110

5. Blood pressure130/85

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

Metabolic Syndrome (Syndrome X)Metabolic Syndrome (Syndrome X)

SteatosisSteatosis

SteatohepatitisSteatohepatitis

CirrhosisCirrhosis

NAFLDSpectrum of Hepatic Pathology

NAFLDSpectrum of Hepatic Pathology

Hepatocellular carcinoma

Hepatocellular carcinoma