Non Alcoholic Fatty Liver dis.. Non alcoholic fatty liver dis. accumulation of macro vesicular fat...
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Transcript of Non Alcoholic Fatty Liver dis.. Non alcoholic fatty liver dis. accumulation of macro vesicular fat...
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
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