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Nafld

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Rahimi management of nafld
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Descripción

alcohol, NASH, NAFLD, Significant alcohol intake, 1 drink , drink, metabolic syndrome, central obesity, dyslipidemia, hypertryglyceridemia, hypertension, diabetes mellitus, pathogenesis of NAFLD, Diagnosis of NAFLD, Diagnosis of NASH, ultrasound, fibroscan, treatment of nafld, fructose rich foods, coffee, coffee in NAFLD, Exercise, weight reduction, metformin, vitamin E, ursodeoxycholic acid, udiliv, pioglitazone, statins, pentoxyfilline

Transcripción

  1. 1. NAFLD
  2. 2. It is defined as accumulation of fat in liver in absence of recent or ongoing intake of Significant amount of alcohol. - Definition also includes the exclusion of other secondary causes of hepatic steatosis. Definition Ref .: position paper of the Indian National Association for liver on NAFLD
  3. 3. About 25% of adults in the United States have fatty livers in the absence of excessive alcohol consumption, a condition termed nonalcoholic fatty liver disease. More than a quarter of adults with nonalcoholic fatty liver disease are presumed to have nonalcoholic steatohepatitis
  4. 4. Significant Alcohol Intake - >1 drink of alcohol for women and >2 drink for men -1 drink = 10gm of alcohol -20 g/day -30ml of whisky =100ml of Wine = 240ml of beer = 10gm of alcohol Ref .: position paper of the Indian National Association for liver on NAFLD
  5. 5. METABOLIC SYNDROME Central obesity. This is measured by waist circumference: • More than 40 inches for men. • More than 35 inches for women Fasting blood triglycerides 150 mg/dL or more HDL cholesterol levels • Men — Less than 40 mg/dL • Women — Less than 50 mg/dL Elevated blood pressure 130/85 mm Hg or higher Fasting glucose (blood sugar) 100 mg/dL or more
  6. 6. Nonalcoholic steatohepatitis is strongly associated with overweight or obesity and the metabolic syndrome. A recent analysis of studies involving more than 8.5 million persons from 22 countries showed that more than 80% of patients with nonalcoholic steatohepatitis are overweight or obese, 72% have dyslipidemia, and 44% have received a diagnosis of type 2 diabetes mellitus. This information supports the concept that nonalcoholic steatohepatitis is the hepatic correlate of the metabolic syndrome.
  7. 7. The ‘first hit’ hepatic triglyceride accumulation, or steatosis, increases susceptibility of the liver to injury mediated by ‘second hits’, such as inflammatory cytokines/adipokines, mitochondrial dysfunction and oxidative stress, which in turn lead to steatohepatitis and/or fibrosis ‘third-hit’ has been added to reflect inadequate hepatocyte proliferation . In the healthy liver, cell death stimulates replication of mature hepatocytes which replace the dead cells and reconstitute normal tissue function.However oxidative stress, a central feature of NAFLD pathogenesis, inhibits the replication of mature hepatocytes which results in expansion of the hepatic progenitor cell (oval cell) Activation of these cells has also been implicated in hepatocellular carcinogenesis.
  8. 8. DIAGNOSIS -Most patients are asymptomatic in beginning or may have vague symptoms of dyspepsia, fatigue or malaise -Incidental finding of fatty liver in ultrasound or elevated liver enzymes in routine evaluation -Anthropometry : reveals overweight or obesity -Biochemistry : normal or mildly elevated Liver enzymes AST and ALT -ALT is more than AST -RULE OUT OTHER CAUSES OF FATTY LIVER
  9. 9. -Anthropometry should be done in all patients irrespective of elevated liver enzymes for assessment of overweight and obesity -LFT -Lipid profile - HbsAg and Anti HCV -Autoimmune markers, celiac disease work up, Iron profile and serum ceruloplasmin should be done only if elevated liver enzymes present
  10. 10. ULTRASOUND - Ultrasound is very effective in diagnosing steatosis where >33% of hepatocytes are steatotic but can be unreliable with lesser degrees of steatosis -Sensitivity of 84.8% and specificity of 93.6% for detecting 20-30% steatosis -Easily available -Inexpensive without any radiation risk -CT and MRI has no added benefit -It cant differentiate between steatosis and steatohepatitis
  11. 11. FIBROSCAN -It is a new non invasive modality which can detect Liver fibrosis -Many patient with fatty liver may turn out to be fibrosis in Fibroscan which completely change the prognosis of condition
  12. 12. TREATMENT OF NAFLD
  13. 13. Lifestyle Modifications Lose 7% of body weight over 6 months if overweight or obese Limit consumption of fructose enriched beverages Limit consumption of alcohol 2 or more cups of caffeinated coffee daily
  14. 14. Fructose rich foods
  15. 15. EXERCISE -45min/day -5days/week -To achieve a target rate of 60-70% of maximal heart rate
  16. 16. WEIGHT REDUCTION -10% of body weight to be reduced in 6-8months -Severe hypo caloric diets are not recommended -Eat fewer calories and burn more calories by regular exercises
  17. 17. -It was found to reduce insulin resistance and mean hepatic aminotransferase levels better than any other drug and in less duration. -It was also found to have improvement in steatosis and fibrosis of liver. -But some other showed no added benefit. -So its use still remains uncertain.
  18. 18. -Pioglitazone 30mg/day for 1 year has been found to show improvement in NASH in all studies -There effect has been found to better in NASH with non diabetic when compared to Diabetic - Side effect : weight gain , edema and worsening of Heart failure.
  19. 19. COFFEE The beneficial effects of coffee are reported for 2 cups/day. One cup is equivalent to 10 g of whole bean coffee and 5 g of instant coffee Coffee will not prevent onset of NAFLD but in a patient of NAFLD , it decreases progression. -Is associated with lower incidence of metabolic syndrome -It decreases Insulin Resistance -Is associated with lower liver enzyme levels. -The protective effect is irrespective of etiology of liver disease -Main mechanism is Antioxidant and prevention of fibrosis. Journal of Clinical and Experimental Hepatology, 2016
  20. 20. COFFEE - Animal studies have shown that coffee decreases expression of transforming growth factor-b and connective tissue growth factor, thus contributing to reduced fibrosis. - It should be noted that caffeine may not be the most important component, as other caffeinated drinks do not provide similar protection against liver disease. - Decrease inflammatory cytokines Anti oxidant effect due to presence of tocopherols and chlorogenic acids Journal of Clinical and Experimental Hepatology, 2016
  21. 21. VITAMIN E -@ Tocopherol - Studies have shown that Vitamin E (400-1200 IU/day orally) if given for 4-12 months and led to significant improvement in Hepatic Aminotransferase - @ Tocopherol 300mg/day was given for 1 year to patients with liver biopsy proven NASH and those with a clinical diagnosis of NAFLD. Hepatic transaminases improved significantly compared to baseline whereas steatosis , fibrosis improved or remain same. 247 adults with nonalcoholic steatohepatitis and without diabetes to receive pioglitazone at a dose of 30 mg daily (80 subjects), vitamin E at a dose of 800 IU daily (84 subjects), or placebo (83 subjects), for 96 weeks. Vitamin E therapy, as compared with placebo, was associated with a significantly higher rate of improvement in nonalcoholic steatohepatitis (43% vs. 19%, P = 0.001),
  22. 22. Ursodeoxycholic Acid -It is a non hepatotoxic epimer of chenodeoxycholic acid( endogenous bile acid) -Endogenous bile acids are hepatotoxic -Ursodeoxycholic acid are non hepatotoxins, has membrane stabilising activity, decreases oxidative stress on liver. -Studied showed no benefit over Placebo therapy when used at a dose of 13- 15mg/kg for 2 years . -Drug is found to be safe with no adverse affects -In few studies only improvement in liver enzymes were noticed after 6 months of therapy. - So to use or not still remains uncertain.
  23. 23. STATINS IN NAFLD -Studies are not much available -Studies till now has not shown any improvement in liver enzymes and histology as compared to placebo. - And they have beneficial role in preventing cardiovascular diseases. As statins can improve the adverse outcomes of other conditions commonly associated with NASH (for example, hyperlipidaemia, diabetes mellitus, metabolic syndrome), their use in patients with non-alcoholic steatohepatitis may be justified.
  24. 24. -Pentoxyfilline 400mg tds for 12months has been found to have significant improvement in both liver enzymes and histology in no. of studies Limitations : Side effects Side Effects 1) Nausea and vomitings 2) M.I 3) Pancytopenia 4) Anaphylactic reactions
  25. 25. RISK FACTOR FOR SEVERE LIVER DISEASE 1) Age >45 2) Female gender 3) AST/ALT >1 4) High APRI 5) Diabetes Mellitus or Metabolic Syndrome present 6) High CK 18
  26. 26. APRI = AST Level (IU/L) AST (Upper limit of normal) Platelet Count (109/L

Descripción

alcohol, NASH, NAFLD, Significant alcohol intake, 1 drink , drink, metabolic syndrome, central obesity, dyslipidemia, hypertryglyceridemia, hypertension, diabetes mellitus, pathogenesis of NAFLD, Diagnosis of NAFLD, Diagnosis of NASH, ultrasound, fibroscan, treatment of nafld, fructose rich foods, coffee, coffee in NAFLD, Exercise, weight reduction, metformin, vitamin E, ursodeoxycholic acid, udiliv, pioglitazone, statins, pentoxyfilline

Transcripción

  1. 1. NAFLD
  2. 2. It is defined as accumulation of fat in liver in absence of recent or ongoing intake of Significant amount of alcohol. - Definition also includes the exclusion of other secondary causes of hepatic steatosis. Definition Ref .: position paper of the Indian National Association for liver on NAFLD
  3. 3. About 25% of adults in the United States have fatty livers in the absence of excessive alcohol consumption, a condition termed nonalcoholic fatty liver disease. More than a quarter of adults with nonalcoholic fatty liver disease are presumed to have nonalcoholic steatohepatitis
  4. 4. Significant Alcohol Intake - >1 drink of alcohol for women and >2 drink for men -1 drink = 10gm of alcohol -20 g/day -30ml of whisky =100ml of Wine = 240ml of beer = 10gm of alcohol Ref .: position paper of the Indian National Association for liver on NAFLD
  5. 5. METABOLIC SYNDROME Central obesity. This is measured by waist circumference: • More than 40 inches for men. • More than 35 inches for women Fasting blood triglycerides 150 mg/dL or more HDL cholesterol levels • Men — Less than 40 mg/dL • Women — Less than 50 mg/dL Elevated blood pressure 130/85 mm Hg or higher Fasting glucose (blood sugar) 100 mg/dL or more
  6. 6. Nonalcoholic steatohepatitis is strongly associated with overweight or obesity and the metabolic syndrome. A recent analysis of studies involving more than 8.5 million persons from 22 countries showed that more than 80% of patients with nonalcoholic steatohepatitis are overweight or obese, 72% have dyslipidemia, and 44% have received a diagnosis of type 2 diabetes mellitus. This information supports the concept that nonalcoholic steatohepatitis is the hepatic correlate of the metabolic syndrome.
  7. 7. The ‘first hit’ hepatic triglyceride accumulation, or steatosis, increases susceptibility of the liver to injury mediated by ‘second hits’, such as inflammatory cytokines/adipokines, mitochondrial dysfunction and oxidative stress, which in turn lead to steatohepatitis and/or fibrosis ‘third-hit’ has been added to reflect inadequate hepatocyte proliferation . In the healthy liver, cell death stimulates replication of mature hepatocytes which replace the dead cells and reconstitute normal tissue function.However oxidative stress, a central feature of NAFLD pathogenesis, inhibits the replication of mature hepatocytes which results in expansion of the hepatic progenitor cell (oval cell) Activation of these cells has also been implicated in hepatocellular carcinogenesis.
  8. 8. DIAGNOSIS -Most patients are asymptomatic in beginning or may have vague symptoms of dyspepsia, fatigue or malaise -Incidental finding of fatty liver in ultrasound or elevated liver enzymes in routine evaluation -Anthropometry : reveals overweight or obesity -Biochemistry : normal or mildly elevated Liver enzymes AST and ALT -ALT is more than AST -RULE OUT OTHER CAUSES OF FATTY LIVER
  9. 9. -Anthropometry should be done in all patients irrespective of elevated liver enzymes for assessment of overweight and obesity -LFT -Lipid profile - HbsAg and Anti HCV -Autoimmune markers, celiac disease work up, Iron profile and serum ceruloplasmin should be done only if elevated liver enzymes present
  10. 10. ULTRASOUND - Ultrasound is very effective in diagnosing steatosis where >33% of hepatocytes are steatotic but can be unreliable with lesser degrees of steatosis -Sensitivity of 84.8% and specificity of 93.6% for detecting 20-30% steatosis -Easily available -Inexpensive without any radiation risk -CT and MRI has no added benefit -It cant differentiate between steatosis and steatohepatitis
  11. 11. FIBROSCAN -It is a new non invasive modality which can detect Liver fibrosis -Many patient with fatty liver may turn out to be fibrosis in Fibroscan which completely change the prognosis of condition
  12. 12. TREATMENT OF NAFLD
  13. 13. Lifestyle Modifications Lose 7% of body weight over 6 months if overweight or obese Limit consumption of fructose enriched beverages Limit consumption of alcohol 2 or more cups of caffeinated coffee daily
  14. 14. Fructose rich foods
  15. 15. EXERCISE -45min/day -5days/week -To achieve a target rate of 60-70% of maximal heart rate
  16. 16. WEIGHT REDUCTION -10% of body weight to be reduced in 6-8months -Severe hypo caloric diets are not recommended -Eat fewer calories and burn more calories by regular exercises
  17. 17. -It was found to reduce insulin resistance and mean hepatic aminotransferase levels better than any other drug and in less duration. -It was also found to have improvement in steatosis and fibrosis of liver. -But some other showed no added benefit. -So its use still remains uncertain.
  18. 18. -Pioglitazone 30mg/day for 1 year has been found to show improvement in NASH in all studies -There effect has been found to better in NASH with non diabetic when compared to Diabetic - Side effect : weight gain , edema and worsening of Heart failure.
  19. 19. COFFEE The beneficial effects of coffee are reported for 2 cups/day. One cup is equivalent to 10 g of whole bean coffee and 5 g of instant coffee Coffee will not prevent onset of NAFLD but in a patient of NAFLD , it decreases progression. -Is associated with lower incidence of metabolic syndrome -It decreases Insulin Resistance -Is associated with lower liver enzyme levels. -The protective effect is irrespective of etiology of liver disease -Main mechanism is Antioxidant and prevention of fibrosis. Journal of Clinical and Experimental Hepatology, 2016
  20. 20. COFFEE - Animal studies have shown that coffee decreases expression of transforming growth factor-b and connective tissue growth factor, thus contributing to reduced fibrosis. - It should be noted that caffeine may not be the most important component, as other caffeinated drinks do not provide similar protection against liver disease. - Decrease inflammatory cytokines Anti oxidant effect due to presence of tocopherols and chlorogenic acids Journal of Clinical and Experimental Hepatology, 2016
  21. 21. VITAMIN E -@ Tocopherol - Studies have shown that Vitamin E (400-1200 IU/day orally) if given for 4-12 months and led to significant improvement in Hepatic Aminotransferase - @ Tocopherol 300mg/day was given for 1 year to patients with liver biopsy proven NASH and those with a clinical diagnosis of NAFLD. Hepatic transaminases improved significantly compared to baseline whereas steatosis , fibrosis improved or remain same. 247 adults with nonalcoholic steatohepatitis and without diabetes to receive pioglitazone at a dose of 30 mg daily (80 subjects), vitamin E at a dose of 800 IU daily (84 subjects), or placebo (83 subjects), for 96 weeks. Vitamin E therapy, as compared with placebo, was associated with a significantly higher rate of improvement in nonalcoholic steatohepatitis (43% vs. 19%, P = 0.001),
  22. 22. Ursodeoxycholic Acid -It is a non hepatotoxic epimer of chenodeoxycholic acid( endogenous bile acid) -Endogenous bile acids are hepatotoxic -Ursodeoxycholic acid are non hepatotoxins, has membrane stabilising activity, decreases oxidative stress on liver. -Studied showed no benefit over Placebo therapy when used at a dose of 13- 15mg/kg for 2 years . -Drug is found to be safe with no adverse affects -In few studies only improvement in liver enzymes were noticed after 6 months of therapy. - So to use or not still remains uncertain.
  23. 23. STATINS IN NAFLD -Studies are not much available -Studies till now has not shown any improvement in liver enzymes and histology as compared to placebo. - And they have beneficial role in preventing cardiovascular diseases. As statins can improve the adverse outcomes of other conditions commonly associated with NASH (for example, hyperlipidaemia, diabetes mellitus, metabolic syndrome), their use in patients with non-alcoholic steatohepatitis may be justified.
  24. 24. -Pentoxyfilline 400mg tds for 12months has been found to have significant improvement in both liver enzymes and histology in no. of studies Limitations : Side effects Side Effects 1) Nausea and vomitings 2) M.I 3) Pancytopenia 4) Anaphylactic reactions
  25. 25. RISK FACTOR FOR SEVERE LIVER DISEASE 1) Age >45 2) Female gender 3) AST/ALT >1 4) High APRI 5) Diabetes Mellitus or Metabolic Syndrome present 6) High CK 18
  26. 26. APRI = AST Level (IU/L) AST (Upper limit of normal) Platelet Count (109/L

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