Non Alcoholic Steatohepatitis
<ul><li>What is it? </li></ul><ul><li>Epidemiology </li></ul><ul><li>Pathogenesis </li></ul><ul><li>Clinical Features and ...
Non alcoholic fatty liver disease <ul><li>Clinico-histopathological entity </li></ul><ul><ul><li>Histological features res...
Epidemiology <ul><li>Occurs worldwide </li></ul><ul><ul><li>Greater in western populations </li></ul></ul><ul><li>USA </li...
Pathogenesis <ul><li>Not fully known </li></ul><ul><li>Insulin resistance </li></ul><ul><li>Additional oxidative injury </...
Excessive Triglyceride accumulation <ul><li>Excessive import of free fatty acids </li></ul><ul><ul><li>Increased delivery ...
Fatty Acids in the Hepatocyte
Insulin Resistance <ul><li>Key role </li></ul><ul><li>Insulin resistance leads to changes in lipid metabolism  </li></ul><...
Insulin Resistance
 
 
Additional defects <ul><li>Antioxidants </li></ul><ul><ul><li>Free radicals deplete antioxidants </li></ul></ul><ul><ul><u...
Clinical Features and Diagnosis <ul><li>Usually asymptomatic </li></ul><ul><li>Fatigue, malaise, abdominal pain </li></ul>...
Clinical Course <ul><li>NAFLD have only slightly lower overall survival than the general population </li></ul><ul><li>Bett...
Treatment <ul><li>No proven effective treatment </li></ul><ul><li>Gradual weight loss </li></ul><ul><ul><li>10% over 6-12 ...
Summary <ul><li>asymptomatic in most cases </li></ul><ul><li>obesity, diabetes mellitus, hypertension and hyperlipidaemia ...
 
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Non Alcoholic Steatohepatitis

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Non Alcoholic Steatohepatitis

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Transcript of "Non Alcoholic Steatohepatitis"

  1. 1. Non Alcoholic Steatohepatitis
  2. 2. <ul><li>What is it? </li></ul><ul><li>Epidemiology </li></ul><ul><li>Pathogenesis </li></ul><ul><li>Clinical Features and Diagnosis </li></ul><ul><li>Clinical Course </li></ul><ul><li>Treatment </li></ul>
  3. 3. Non alcoholic fatty liver disease <ul><li>Clinico-histopathological entity </li></ul><ul><ul><li>Histological features resemble alcohol induced liver disease </li></ul></ul><ul><li>Associated with negligible or no alcohol intake </li></ul><ul><li>Spectrum of disease </li></ul><ul><ul><li>Steatosis </li></ul></ul><ul><ul><li>Steatohepatitis </li></ul></ul><ul><ul><li>cirrhosis </li></ul></ul><ul><li>Leading cause of cryptogenic cirrhosis </li></ul><ul><li>Increasingly recognised </li></ul>
  4. 4. Epidemiology <ul><li>Occurs worldwide </li></ul><ul><ul><li>Greater in western populations </li></ul></ul><ul><li>USA </li></ul><ul><ul><li>3% of lean individuals </li></ul></ul><ul><ul><li>19% of obese </li></ul></ul><ul><ul><li>50% of morbidly obese/diabetics </li></ul></ul><ul><li>♀ > ♂ </li></ul><ul><li>Associated with type 2 diabetes, obesity, hypertension and hyperlipidaemia </li></ul>
  5. 5. Pathogenesis <ul><li>Not fully known </li></ul><ul><li>Insulin resistance </li></ul><ul><li>Additional oxidative injury </li></ul>
  6. 6. Excessive Triglyceride accumulation <ul><li>Excessive import of free fatty acids </li></ul><ul><ul><li>Increased delivery (obesity, rapid weight loss) </li></ul></ul><ul><ul><li>Excess conversion of carbohydrates and proteins to triglycerides (overfeeding, TPN) </li></ul></ul><ul><li>Reduced export of FFA </li></ul><ul><ul><li>Impaired VLDL synthesis or secretion </li></ul></ul><ul><li>Impaired beta-oxidation of FFA to ATP </li></ul>
  7. 7. Fatty Acids in the Hepatocyte
  8. 8. Insulin Resistance <ul><li>Key role </li></ul><ul><li>Insulin resistance leads to changes in lipid metabolism </li></ul><ul><ul><li>Increased peripheral lipolysis, triglyceride synthesis and hepatic uptake of FFA </li></ul></ul><ul><li>Shift from carbohydrate to FFA beta oxidation </li></ul><ul><li>Free fatty acids </li></ul><ul><ul><li>Inducers of cytochrome p-450 </li></ul></ul><ul><ul><li>Leads to hepatotoxic free oxygen radical species </li></ul></ul>
  9. 9. Insulin Resistance
  10. 12. Additional defects <ul><li>Antioxidants </li></ul><ul><ul><li>Free radicals deplete antioxidants </li></ul></ul><ul><ul><ul><li>Glutathione, vit E, beta-carotene, vit C </li></ul></ul></ul><ul><li>Iron </li></ul><ul><ul><li>Insulin resistance associated with increased hepatic iron levels </li></ul></ul><ul><ul><li>Heterozygous for the haemochromatosis gene mutation </li></ul></ul><ul><li>Leptin </li></ul><ul><ul><li>Deficiency leads to massive obesity </li></ul></ul><ul><ul><li>Leptin may contribute to development of fibrosis </li></ul></ul><ul><li>Intestinal Microbes </li></ul><ul><ul><li>Endogenous ethanol and acetaldehyde production which leads to hepatic injury </li></ul></ul><ul><ul><li>Endotoxin production </li></ul></ul>
  11. 13. Clinical Features and Diagnosis <ul><li>Usually asymptomatic </li></ul><ul><li>Fatigue, malaise, abdominal pain </li></ul><ul><li>Often incidental diagnosis </li></ul><ul><li>AST and ALT elevated in 90% </li></ul><ul><ul><li>AST/ALT < 1 </li></ul></ul><ul><li>Liver biopsy </li></ul>
  12. 14. Clinical Course <ul><li>NAFLD have only slightly lower overall survival than the general population </li></ul><ul><li>Better prognosis than alcoholic hepatitis </li></ul><ul><ul><li>Alcoholic hepatitis </li></ul></ul><ul><ul><ul><li>38 to 50% progress to cirrhosis </li></ul></ul></ul><ul><ul><li>NASH </li></ul></ul><ul><ul><ul><li>8 to 26 % progress to cirrhosis </li></ul></ul></ul><ul><li>Little change in LFTs throughout course of disease </li></ul><ul><li>Can recur following transplant </li></ul>
  13. 15. Treatment <ul><li>No proven effective treatment </li></ul><ul><li>Gradual weight loss </li></ul><ul><ul><li>10% over 6-12 months </li></ul></ul><ul><li>Associated diabetes, hypertension and hyperlipidaemia should be treated </li></ul><ul><li>Vitamin E </li></ul><ul><li>Metformin </li></ul><ul><li>Pioglitazone </li></ul>
  14. 16. Summary <ul><li>asymptomatic in most cases </li></ul><ul><li>obesity, diabetes mellitus, hypertension and hyperlipidaemia are frequent associated features </li></ul><ul><li>increase plasma ALT the commonest liver function test abnormality </li></ul><ul><li>NASH accounts for most cases of isolated increased plasma transaminase activity of otherwise unknown cause </li></ul><ul><li>liver biopsy rarely needed </li></ul><ul><li>long-term prognosis is favourable </li></ul><ul><li>graduated weight loss is the best available treatment </li></ul>

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