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Enfermedad por Hígado Graso y Obesidad Infantil Dr. José Luis Gonzáles  Gastroenterología Noviembre 2009
Steatosis Steatohepatitis Cirrhosis Hepatocellular carcinoma Non Alcoholic Fatty Liver Disease (NAFLD) Spectrum of Hepatic Pathology
 
 
The Hypothalamic-Leptin Axis How it works: ,[object Object],[object Object],[object Object],[object Object],[object Object]
What blocks leptin? ,[object Object],[object Object],[object Object],[object Object]
Insulin excess blocks leptin Lustig,  Ped Annals , 35:12 Dec 2006
INSULIN RESISTANCE AND FAT DEPOSITION Insulin resistance  Free Fatty Acids Insulin resistance Insulin resistance insulin Liver Muscle
Hepatic Steatosis Gender Disparities in Whites Hispanics Whites Blacks 45% 42% 24% FLD 24% M M M F F F
TV + Food = Overweight
Enfermedad de Hígado Graso No Alcohólico Esteatohepatitis no Alcohólica NAFLD
Enfermedad de Hígado Graso No Alcohólico ,[object Object],[object Object]
[object Object],[object Object],[object Object]
 
NON-ALCOHOLIC FATTY LIVER DISEASE ,[object Object],[object Object],[object Object],[object Object],[object Object]
NON-ALCOHOLIC FATTY LIVER DISEASE ,[object Object],[object Object],[object Object],[object Object]
Prevalence of Elevated Alanine Aminotransferase Among US Adolescents and Associated Factors: NHANES 1999–2004 ,[object Object],[object Object],[object Object]
Elevated Alanine Aminotransferase Among US Adolescents
Elevated Alanine Aminotransferase Among US Adolescents
Elevated Alanine Aminotransferase Among US Adolescents ,[object Object],[object Object],GASTROENTEROLOGY 2007;133:1814–1820
The Problem: Non-alcoholic Fatty Liver Disease in Your Practice and Interpretation of ALT Levels ,[object Object],[object Object],[object Object],[object Object],[object Object]
Elevated Alanine Aminotransferase Among US Adolescents ,[object Object],[object Object],GASTROENTEROLOGY 2007;133:1814–1820
NAFLD ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Causa ,[object Object],[object Object],[object Object],[object Object]
Fatty Liver:  Macrovescicular steatosis with nucleus  positioning at cell periphery NASH:   Mallory bodies, ballooning degeneration, lobular neutrophil inflammation and perisinusoidal fibrosis AGA Technical Review on Nonalcoholic Fatty Liver Disease Gastroenterology  2002;123:1705-1725 NAFLD
NAFLD ,[object Object],Fatty Liver Obese BMI>28 Centipetal (apple) Bright liver on USS Insulin Resistance Normal  ALT NASH Obese BMI>28 Bright liver on USS Abnormal  ALT Features of metabolic syndrome Dyslipidaemia DM HBP Cirrhosis Bright/ small liver on USS + splenomegaly Abnormal  ALT Thrombocytopenia Obesity Poorly controlled  DM Poorly controlled lipids Hypertension 2 nd  hit
NASH Steatosis Cirrhosis
NASH- Peri-sinusiodal fibrosis
Grading and Staging of NAFLD Grading NAFLD 1.Macrovescicular steatosis Grade 0: None Grade 1: Up to 33% Grade 2: 33%-66% Grade 3: >66% 2. Necroinflammatory activity  Mild, Mod, Severe Brunt et al  Am J Gastro  1999
 
Diseases associated with Steatohepatitis ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
 FFA oxidation  Lipogenesis  Lipid Export Hepatic Steatosis High Fat/CHO Diet Lack of Exercise Pathogenesis of NASH Insulin Resistance White Adipose Tissue Adipokines- adiponectin Cytokines-  TNF   IL-6    Oxidative Stress Endotoxin Cytokines ROS Toxins NASH Peroxidation of  hepatocyte membrane Cytokine release Stellate cell activation 2 nd  Hit
 FFA oxidation  Lipogenesis  Lipid Export Hepatic Steatosis High Fat/CHO Diet Lack of Exercise Pathogenesis of NASH  CellularFFA Insulin Resistance I  B and NF  B activation  IL6 &TNF α
 FFA oxidation  Lipogenesis  Lipid Export Hepatic Steatosis High Fat/CHO Diet Lack of Exercise Pathogenesis of NASH  CellularFFA Insulin Resistance  GLUT 4 activity Reduced glucose entry into cells
 FFA oxidation  Lipogenesis  Lipid Export Hepatic Steatosis High Fat/CHO Diet Lack of Exercise Treatment Strategies In NASH Insulin Resistance White Adipose Tissue Adipokines- adiponectin Cytokines-  TNF   IL-6    Oxidative Stress Endotoxin Cytokines ROS Toxins NASH Peroxidation of  hepatocyte membrane Cytokine release Stellate cell activation 2 nd  Hit Diet &Exercise Orlistat Sibutramine Rimonabant Statins Gemfibrozil Metformin Pioglitazone Rosiglitazone Diet &Exercise Probiotics Antioxidants Bariatric Surgery
SINTOMAS DE NAFLD/NASH ,[object Object],[object Object]
NAFLD NASH DIAGNOSIS ,[object Object],[object Object],[object Object],[object Object]
NAFLD NASH: Tx ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object]
Current Management of |NAFLD and NASH.  APT.  Younossi Z: 2008
Natural history ,[object Object],[object Object],[object Object]
NASH ,[object Object],[object Object],[object Object]
Non-alcoholic fatty liver ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

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Hígado graso no alcohólico en niños y adolescentes obesos

  • 1. Enfermedad por Hígado Graso y Obesidad Infantil Dr. José Luis Gonzáles Gastroenterología Noviembre 2009
  • 2. Steatosis Steatohepatitis Cirrhosis Hepatocellular carcinoma Non Alcoholic Fatty Liver Disease (NAFLD) Spectrum of Hepatic Pathology
  • 3.  
  • 4.  
  • 5.
  • 6.
  • 7. Insulin excess blocks leptin Lustig, Ped Annals , 35:12 Dec 2006
  • 8. INSULIN RESISTANCE AND FAT DEPOSITION Insulin resistance Free Fatty Acids Insulin resistance Insulin resistance insulin Liver Muscle
  • 9. Hepatic Steatosis Gender Disparities in Whites Hispanics Whites Blacks 45% 42% 24% FLD 24% M M M F F F
  • 10. TV + Food = Overweight
  • 11. Enfermedad de Hígado Graso No Alcohólico Esteatohepatitis no Alcohólica NAFLD
  • 12.
  • 13.
  • 14.  
  • 15.
  • 16.
  • 17.
  • 18. Elevated Alanine Aminotransferase Among US Adolescents
  • 19. Elevated Alanine Aminotransferase Among US Adolescents
  • 20.
  • 21.
  • 22.
  • 23.
  • 24.
  • 25. Fatty Liver: Macrovescicular steatosis with nucleus positioning at cell periphery NASH: Mallory bodies, ballooning degeneration, lobular neutrophil inflammation and perisinusoidal fibrosis AGA Technical Review on Nonalcoholic Fatty Liver Disease Gastroenterology 2002;123:1705-1725 NAFLD
  • 26.
  • 29. Grading and Staging of NAFLD Grading NAFLD 1.Macrovescicular steatosis Grade 0: None Grade 1: Up to 33% Grade 2: 33%-66% Grade 3: >66% 2. Necroinflammatory activity Mild, Mod, Severe Brunt et al Am J Gastro 1999
  • 30.  
  • 31.
  • 32.  FFA oxidation  Lipogenesis  Lipid Export Hepatic Steatosis High Fat/CHO Diet Lack of Exercise Pathogenesis of NASH Insulin Resistance White Adipose Tissue Adipokines- adiponectin Cytokines- TNF IL-6 Oxidative Stress Endotoxin Cytokines ROS Toxins NASH Peroxidation of hepatocyte membrane Cytokine release Stellate cell activation 2 nd Hit
  • 33.  FFA oxidation  Lipogenesis  Lipid Export Hepatic Steatosis High Fat/CHO Diet Lack of Exercise Pathogenesis of NASH  CellularFFA Insulin Resistance I  B and NF  B activation  IL6 &TNF α
  • 34.  FFA oxidation  Lipogenesis  Lipid Export Hepatic Steatosis High Fat/CHO Diet Lack of Exercise Pathogenesis of NASH  CellularFFA Insulin Resistance  GLUT 4 activity Reduced glucose entry into cells
  • 35.  FFA oxidation  Lipogenesis  Lipid Export Hepatic Steatosis High Fat/CHO Diet Lack of Exercise Treatment Strategies In NASH Insulin Resistance White Adipose Tissue Adipokines- adiponectin Cytokines- TNF IL-6 Oxidative Stress Endotoxin Cytokines ROS Toxins NASH Peroxidation of hepatocyte membrane Cytokine release Stellate cell activation 2 nd Hit Diet &Exercise Orlistat Sibutramine Rimonabant Statins Gemfibrozil Metformin Pioglitazone Rosiglitazone Diet &Exercise Probiotics Antioxidants Bariatric Surgery
  • 36.
  • 37.
  • 38.
  • 39.
  • 40. Current Management of |NAFLD and NASH. APT. Younossi Z: 2008
  • 41.
  • 42.
  • 43.

Notes de l'éditeur

  1. 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.
  2. Changes slowly in days to weeks
  3. Hypothalamic obesity syndrome is incredibly rare. Later, fructose…
  4. Adi Adipose tissue in obesity becomes refracdtory to insulins suppression of fat mobilization., Insulin resistance increases the release of FFA from the adipcyte. In the postprandial period there is an excess of FFA leading to fat deponsition in other tissues Hytperinsulinemiua stimulates fatty acid synthesi while inhibiting the oxidation of fatty acids.,sElevagted insulin may increase the degradation of apolipoprotein B100a component of VLDLcompromising triglyceride transport out of the liver causing anet accumulation of fat. ElevatedFFA and accumulagted triacylglycerol appear to inhibit insulin signalling leading to a reduction in insulin stimulated muscleglucose transporty,.The reduced muscle glucose transport leads to reduced glycogen syntethisisand glycolysis
  5. Another interesting result of this study pertained to gender-related differences in hepatic steatosis. The latter was noted only in the Caucasian population, in which men were almost twice as likely as women to have fatty livers. In other ethnic subgroups, the prevalence of hepatic steatosis was similar in men and women.
  6. Bad combination ! Many studies lately…