1 fatty liver: afld & nafld1. fatty liver: afld & nafld 2
TRANSCRIPT
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1 Fatty Liver: AFLD & NAFLD1 Fatty Liver: AFLD & NAFLD1 Fatty Liver: AFLD & NAFLD1 Fatty Liver: AFLD & NAFLD1. Fatty Liver: AFLD & NAFLD1. Fatty Liver: AFLD & NAFLD2. Drug hepatitis2. Drug hepatitis1. Fatty Liver: AFLD & NAFLD1. Fatty Liver: AFLD & NAFLD2. Drug hepatitis2. Drug hepatitisg pg p3. Iron overload disorders3. Iron overload disorders
hemosiderosishemosiderosis
g pg p3. Iron overload disorders3. Iron overload disorders
hemosiderosishemosiderosis--hemosiderosishemosiderosis--hereditary hemochromatosishereditary hemochromatosis--hemosiderosishemosiderosis--hereditary hemochromatosishereditary hemochromatosisyy
4. Copper overload4. Copper overload——Wilson diseaseWilson disease5 Al h5 Al h 11 tit i d fi itit i d fi i
yy4. Copper overload4. Copper overload——Wilson diseaseWilson disease5 Al h5 Al h 11 tit i d fi itit i d fi i5. Alpha5. Alpha--11--antitrypsin deficiencyantitrypsin deficiency5. Alpha5. Alpha--11--antitrypsin deficiencyantitrypsin deficiency
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Fatty liver and possible sequelae
AFLD ASH Cirrhosis(alcoholic fatty liver dis.) alcoholic steatohepatitis
NAFLD NASH Cirrhosis( l h li f li l h li h i i(non-alcoholic fatty liver non-alcoholic steatohepatitisdisease)
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oxidative stress-steatosis-copper overload
Mallory bodyhepatocyte
Mallory body
p62cytokeratins 8 + 18 p62
ubiquitin
PATHOGENESIS OF MALLORY BODIES
ubiquitin
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t ll t ll ti ti tstellate cell activation tomyofibroblasts fibrosis
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Alcoholic Non-alcoholic
Hit 1obesitydiabetes
AFLD NAFLD
Hit 1:causes fat
acetaldehyde diabetesmetabolic syndrome
(alcoholic fatty liver disease) (non-alcoholic fatty liver disease)
Hit 2:causes steatohepatitis
ASH NASH(alcoholic steatohepatitis) (non-alcoholic steatohepatitis)
•cytokines•endotoxin
TWO-HIT HYPOTHESIS of STEATOHEPATITIS
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Drug/ChemicalHepatotoxicity
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Veno-occlusive disease (VOD): pyrrolizidine alkaloids (“bush tea”)
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O l C t tiOral Contraceptives•cholestasis• liver-cell adenoma•peliosis hepatispeliosis hepatis
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Metal storage diseases:Metal storage diseases:Fe and CuFe and Cu
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Iron Overload DisordersIron Overload Disorders
P i I O l d• Primary Iron Overload-hereditary hemochromatosis-hereditary hemochromatosis
• Secondary Iron Overload• Secondary Iron Overload-transfusion/hemolysis/t a s us o / e o ys s/-hemodialysis
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Kupffer cell hemosiderosis: hemolysis—transfus.--hemodialysis
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1889: von Recklinghausen: “hemochromatosis”(“bronzed diabetes”)( bronzed diabetes )
-85-100% due to HFE mutation (C282Y/C282Y)
-<5% due to other non-HFE mutations
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Hereditary HemochromatosisHereditary Hemochromatosis
• Type 1: HFE (C282Y)• Type 2: Juvenile hemochromatosis• Type 2: Juvenile hemochromatosis
-hemojuvelin: 2A-HAMP: 2B
• Type 3: TfR2• Type 3: TfR2• Type 4: Ferroportin
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