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H EPATITIS VIRAL INFECTION and NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) : AN UPDATE

H EPATITIS VIRAL INFECTION and NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) : AN UPDATE. L.A. Lesmana Department of Medicine, University of Indonesia , Jakarta. NALFD – AAS LD definition 2012 . Evidence of hepatic steatosis, by imaging or by histology,

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H EPATITIS VIRAL INFECTION and NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) : AN UPDATE

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  1. HEPATITIS VIRAL INFECTION andNON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) : AN UPDATE L.A. Lesmana Department of Medicine, University of Indonesia , Jakarta

  2. NALFD – AASLD definition 2012 • Evidence of hepatic steatosis, by imaging or by histology, • No causes for secondary hepatic fat accumulation Chalasani N, et al. Gastroenterology 2012;142:1592-1609.

  3. Prevalence of NAFLD in the Asia-Pacific region Country Percentage of NAFLD • Japan 9 – 30% • China 5 – 18% • Korea 18 % • India 5 – 28% • Indonesia 30% • Malaysia 17 % • Singapore 5% Amarapurkar. Asia Pacific Working Party on NAFLD 2006

  4. Insulin Resistance and Hepatitis p<0.005 p<0.005 Imazeki et al. Liver Int 2008:355-62

  5. Chronic Hepatitis B (CHB) and NAFLD Current Evidence

  6. Prevalence of steatosis in CHB Thomopoulos KC, et al. Eur J Gastroenterol Hepatol 2006;18:233-7 Altlparmak E, et al. World J Gastroenterol 2005;11:3056-9. Gordon A, et al. J Hepatol 2005;43:38-44. Peng D, et al. J GastroenterolHepatol 2008;23:1082-8. • Bondini S, et al. Liver Int 2007;27:607-11. • Rastogi A. et al. Indian J Pathol Microbiol 2011;54:454-9. • Lesmana LA, et al. Acta Med Indones 2012;44:35-9.

  7. Factors associated with FL in CHB Altlrmak E , et al. World J Gastroenterol 2005;11:3056-9.

  8. Insulin Resistance in CHB Kumar M, et al. Am J Gastroenterol 2009;104:76-82.

  9. Demographic Factors Rastogi A. et al. Indian J Pathol Microbiol 2011;54:454-9. Medistra Hospital. Unpublished data 2007-2009

  10. Biochemical and Viral Factors Rastogi A. et al. Indian J Pathol Microbiol 2011;54:454-9.

  11. Metabolic Parameters BMI: body mass index; FBS: fasting blood sugar; TG: triglycerides; HOMA-IR: Homeostatic Model of Assessment – Insulin Resistance Rastogi A. et al. Indian J Pathol Microbiol 2011;54:454-9.

  12. Histological Features HAI: histological activity index Rastogi A. et al. Indian J Pathol Microbiol 2011;54:454-9.

  13. Data in Medistra Hospital Lesmana LA, et al. Acta Med Indones 2012;44:35-9.

  14. Histological Features Fibrosis stage Inflammatory grade p = 0.849 p = 0.624 Lesmana LA, et al. Acta Med Indones 2012;44:35-9.

  15. Predictors of Steatosis in CHB

  16. Fatty Liver vs. SVR Rates FL did not affect IFN-based treatment outcomes (p > 0.005) Cindoruk M, et al. J ClinGastroenterol 2007;41:513-7.

  17. Immune control – inactive disease Immune Immune Immune Escape/ Immune Tolerant Control Reactivation Clearance HBeAg– HBeAg+ HBV DNA ALT HBeAg +Chronic Hepatitis B Inactive Carrier Status HBeAg – Chronic HBV Immune control – treatment not required

  18. Summary: NAFLD in CHB • NAFLD is commonly found in about one-third of patients. • NAFLD in CHB is strongly associated with metabolic factors, e.g.: body mass index (BMI), obesity, insulin resistance, dyslipidemia. • NAFLD is not associated with liver fibrosis or histological activity index. • NAFLD may not affect treatment response. • In patients with CHB and NAFLD with elevated ALT in clinical practice is not easy to distinguish whether the high ALT is due to CHB or NAFLD.

  19. Chronic Hepatitis C (CHC) and NAFLD Current Evidence

  20. Risk factors of FL in Chronic Hep C Fatty liver is associated with features of metabolic syndrome in patients with chronic hepatitis C virus infection. Sanyal AJ, et al. Am J Gastroenterol 2003;98:2064-71

  21. IR and Liver Fibrosis in CHC p = 0.002 Insulin resistance is associated with more advanced fibrosis in patients with chronic hepatitis C virus infection Taura N, et al. Am J Gastroenterol 2006;101:2752-9.

  22. HCV GENOTYPE DISTRIBUTION % Subjects: 68 chronic hepatitis, 48 cirrhosis, and 34 HCC Method: core sequence analyses HCV genotype 1b is predominant in Indonesia Utama A, et al. Liver Int 2010;30:1152-60.

  23. RVR: rapid virologic response (HCV RNA <43 IU/mL at week-4 ) • SVR: sustained virologic response (HCV RNA <15 IU/mL at week-48 p=0.001 Relapse rate are higher in patients infected with HCV genotype 3 who have an RVR Shah SR, et al. ClinGastroenterolHepatol 2011;9:688-93.

  24. OR: 3.0; 95%CI: 1,5-6.1; p=0.003 Steatosis vs. no steatosis HCV RNA > vs. < 400.000 IU/mL BMI >vs < 30 kg/m2 Age >vs <45 years GGT > vs< ULN OR: 2.5; 95%CI: 1,0-6.3; p=0.04 OR: 2.2; 95%CI: 1,0-4.8; p=0.04 OR: 2.2; 95%CI: 1,2-4.2; p=0.02 OR: 2.1; 95%CI: 1,1-4.1; p=0.03 -2 -1 0 1 2 3 4 5 6 7 8 Steatosisis the strongest independent predictor of relapse in patients infected with HCV genotype 3 who have an RVR Shah SR, et al. ClinGastroenterolHepatol 2011;9:688-93.

  25. HCV infection and Metabolic Syndrome • There is no evidence for association between HCV infection and metabolic syndrome. • The 2 conditions occur together at a higher rate than would occur by chance, although HCV infection has been associated with type2 diabetes mellitus. • The serum lipid profile of patients with HCV infections is characterized by decreased level of cholesterol and sometimes triglycerides,in contrast to metabolic syndrome Negro F. Gastroenterology 2012;142:1288-92

  26. HCV and Lipid Metabolism that may lead to steatosis of hepatocytes Negro F. Gastroenterology 2012;142:1288-92.

  27. HCV might affect insulin signaling in hepatocytes contributing to Insulin Resistance Negro F. Gastroenterology 2012;142:1288-92.

  28. Possible Clinical Outcomes • Insulin resistance in CHC have substantial impact on the morbidity and mortality : • Accelerated progression of liver fibrosis • Increase type 2 diabetes • Reduced virological response to antiviral therapy • Increase incidence of cardiovascular events  need further study Bugianesi E, et al. J Hepatol 2012;56(Suppl ):S56-S65

  29. Summary: NAFLD in CHC • NAFLD is frequently found in CHC • Its present is genotype specific, mostly genotype 1 and 3 • Alcohol, central obesity, raised BMI are associated with more activity and more severe fibrosis • Obesity reduces response to IFN-based treatment • NAFLD may increase relapse rate among previously rapid virologic responders

  30. THANK YOU

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