Management of NAFLD in 2007


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Management of NAFLD in 2007

  1. 1. How Should We Manage Patients with NAFLD in 2007 Henry LY Chan, MD, FRCP Professor Department of Medicine and Therapeutics The Chinese University of Hong Kong
  2. 2. Diagnosis of Fatty Liver <ul><li>USG; CT if US not informative </li></ul><ul><li>Imaging can detect > 33% fat on liver biopsy Saadeh S et al., Gastroenterology 2002 </li></ul><ul><li>Cannot differentiate steatosis from steatohepatitis </li></ul><ul><li>Liver biopsy is usually not needed to </li></ul><ul><li> diagnose fatty liver disease </li></ul>
  3. 3. AFLD vs NAFLD <ul><li>Alcohol consumption to define NAFLD (g/wk) </li></ul>Faick-Ytter et al., Semin Liver Dis 2001 Metteoni (1999) Bonkovsky (1999) George (1998) Lee (1989) Teli (1995) Angulo (1999) Diehl (1988) Bacon (1994) Powell (1996) Ludwig (1980) 140 40 0
  4. 4. Exclude other Liver D isease <ul><li>HBV – HBsAg, (HBV DNA) </li></ul><ul><li>HCV – anti-HCV, (HCV RNA) </li></ul><ul><li>Autoimmune hepatitis – ANA </li></ul><ul><li>Alfa-1 anti-trypsin deficiency </li></ul><ul><li>Wilson’s disease </li></ul><ul><li>Hepatic malignancy </li></ul><ul><li>Hepatic infection </li></ul><ul><li>Biliary disease </li></ul>
  5. 5. Liver biopsy Steatohepatitis = fat accumulation + ballooning degeneration ± Mallory hyaline or fibrosis <ul><li>Recommendation for liver biopsy </li></ul><ul><li>Diagnostic uncertainty </li></ul><ul><li>High risk of advanced fibrosis </li></ul><ul><li>Clinical trial </li></ul><ul><li>With laparoscopic procedure/surgery </li></ul>Matteoni CA, et al. Gastroenterology 1999 10.9% 24.6% 73 Steatohepatitis 1.7% 3.3% 59 Simple steatosis Liver-related death Cirrhosis N
  6. 6. Advanced NAFLD <ul><li>Clinical factors </li></ul><ul><ul><li>Advanced age </li></ul></ul><ul><ul><li>Diabetes mellitus </li></ul></ul><ul><ul><li>Obesity </li></ul></ul>0 4 8 12 16 0.25 0.20 0.15 0.10 0.05 0 El-Serag and Everharts, Gastroenterology, 2004 DM No DM % HCC
  7. 7. Serum biomarker <ul><li>AST/ALT ratio </li></ul><ul><li>Serum hyaluronic acid </li></ul><ul><li>HOMA score </li></ul><ul><li>Plasma homocysteine </li></ul><ul><li>Triglyceride </li></ul><ul><li>Adiponectin </li></ul><ul><li>Steatotest </li></ul><ul><li>Fibrotest </li></ul>Accuracy was seldom above 75-80% Cannot substitute liver biopsy Guha et al, Gut 2006 Sebastian et al, WJG 2006
  8. 8. Metabolic Syndrome High fasting glucose ≥ 6.1 mmol/l or pervious diagnosed type 2 diabetes High fasting glucose ≥ 6.1 mmol/l High BP ≥ 130/85 mmHg or medication High BP ≥ 130/85 mmHg Low HDL-C < 1.03 mmol/l (M), < 1.29 mmol/l (F) or medication Low HDL-C < 1.03 mmol/l (M), < 1.29 mmol/l (F) Hypertriglyceridaemia TG ≥ 1.7 mmol/l or medication Hypertriglyceridaemia TG ≥ 1.7 mmol/l Central obesity Central obesity plus any 2 of the following 3 of the following IDF 2005 ATP III 2001
  9. 9. OGTT recommended in patients without known DM and normal fasting glucose High fasting blood glucose alone High fasting glucose +/- 2-hr post-prandial glucose NAFLD Control Wong VW et al., Aliment Pharmacol Ther 2006 50% 40% 30% 20% 10% 36% 12% 14% 2% IGT DM 50% 40% 30% 20% 10% 33% 14% 23% 7% IGT DM
  10. 10. Diet <ul><li>No association between total caloric or protein vs severity of NAFLD </li></ul><ul><li>Soiga et al, Dig Dis Sci 2004 </li></ul><ul><li>Low carbohydrate and low fat diet </li></ul><ul><ul><li>Weight loss </li></ul></ul><ul><ul><li>Lower BMI </li></ul></ul><ul><ul><li>Lower insulin resistance </li></ul></ul><ul><ul><li>? Some benefit in NAFLD </li></ul></ul><ul><ul><li>Huang et al., Am J Gastroenterol 2005 </li></ul></ul><ul><ul><li>Daubioul et al. Eur J Clin Nutr 2005 </li></ul></ul>
  11. 11. Physical Activity <ul><li>Aerobic exercise with dietary restriction can improve insulin resistance and liver disease in NAFLD in human </li></ul><ul><li>Cinar et al., JGH 2006 </li></ul><ul><li>Nobili et al., Hepatology 2006 </li></ul><ul><li>Kugelmas et al., Hepatol 2003 </li></ul><ul><li>Ueno et al., J Hepatol 1997 </li></ul><ul><li>Suzuki et al, J Hepatol 1005 </li></ul><ul><li>Hicknam et al, Gut 2004 </li></ul><ul><li>Screenivasa et al, JGH 2006 </li></ul><ul><li>Randomized controlled studies lacking </li></ul>
  12. 12. Pharmacological Treatment Adams and Angulo, Postgrad Med J 2006 Pharmacological treatment for NAFLD remains investigational Probucol Statins Pentoxifyline Angiotensin II inhibitor Betaine Vitamin C or E Thiazolidinediones Ursodeoxycholic acid Metformin No Benefit Controversial or Preliminary
  13. 13. Use of Statins in NAFLD <ul><li>Statins are safe in NAFLD </li></ul><ul><li>Recommended if clinically indicated for treatment of metabolic syndrome </li></ul><ul><li>Frequent monitoring of liver enzymes is not required </li></ul>Chalasani et al., Hepatology 2005
  14. 14. Bariatric surgery <ul><li>Bariatric surgery can induce weight loss and improve steatosis and ALT in patients with NAFLD </li></ul><ul><li>Effect on inflammation and fibrosis variable </li></ul><ul><li>Recommended for morbidly obese patients, particularly for those failed dietary restriction and exercise </li></ul><ul><li>Dixon et al, Hepatology 2004 </li></ul><ul><li>Kral et al., Surgery 2004 </li></ul><ul><li>Luyckx et al, Int J Oes Ralat Metab Disord 1998 </li></ul><ul><li>Silverman et al, Am J Clin Pathol 1995 </li></ul>
  15. 15. Proposal 5 <ul><li>Exclude secondary causes of fatty liver </li></ul><ul><li>Assess for severity of NAFLD </li></ul><ul><li>Screen and treat metabolic risk factors </li></ul><ul><li>Lifestyle modification (+/- some weight reduction) to reduce insulin resistance </li></ul><ul><li>Bariatric surgery for morbidly obese who fails lifestyle measures </li></ul><ul><li>Pharmacological treatment is not recommended as routine practice </li></ul>