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Steatosis Steato-hepatitis (NASH) Cirrhosis HUMANS Obesity Causes Non-Alcoholic Fatty Liver Disease (NAFLD) Spectrum of Hepatic Pathology Hepatocellular carcinoma
Cirrhosis MICE Obesity Promotes Liver Inflammation and Cancer by  Enhancing Pro-Inflammatory Cytokines Inflammation
Human NAFLD: Where Are We? ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Where Should We Go? ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Where Should We Go? ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Cohorts For GWAS, Metagenomics  & Biomarkers  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Where Should We Go? ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Cannabinoids Affect  Liver Inflammation and Fibrosis Sophie Lotersztajn and colleagues, Nat Med 2006  38 French Academic Labs Dedicated to Liver Diseases: Aviesan Identify  Targets of New Molecules For NAFLD
gp130 Mutations in Inflammatory  Hepatocellular Tumors Jessica Zucman-Rossi and colleagues, Nature 2009   38 French Academic Labs Dedicated to Liver Diseases: Aviesan Identify  Targets of New Molecules For NAFLD gp130 IL-6 IL-6R
Tumor Samples Are Already Available: French Collection of Liver Tumors BIOBANKS INSTITUTIONS USE ,[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]
Where Should We Go? ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Liver Units in French Academic Health Centers (AHCs) For Randomized Clinical Trials (RCTs)  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
The ‘Anti-inflammatory’ Pentoxifylline For Patients With Advanced Cirrhosis   Marcellin et al. N Engl J Med 2008 Tenofovir vs. Adefovir For Chronic Hepatitis B Telaprevir and Peginterferon With or Without Ribavirin  For Chronic Hepatitis C Hézode et al. N Engl J Med 2009 Lebrec et al. Gastroenterology 2010  Survival Without Complications Pentoxifylline (n=164) Placebo (n=171) P =0.03
Conclusions ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

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08 rencontres biomédicale LIR Richard Moreau

  • 1.
  • 2. Steatosis Steato-hepatitis (NASH) Cirrhosis HUMANS Obesity Causes Non-Alcoholic Fatty Liver Disease (NAFLD) Spectrum of Hepatic Pathology Hepatocellular carcinoma
  • 3. Cirrhosis MICE Obesity Promotes Liver Inflammation and Cancer by Enhancing Pro-Inflammatory Cytokines Inflammation
  • 4.
  • 5.
  • 6.
  • 7.
  • 8.
  • 9. Cannabinoids Affect Liver Inflammation and Fibrosis Sophie Lotersztajn and colleagues, Nat Med 2006 38 French Academic Labs Dedicated to Liver Diseases: Aviesan Identify Targets of New Molecules For NAFLD
  • 10. gp130 Mutations in Inflammatory Hepatocellular Tumors Jessica Zucman-Rossi and colleagues, Nature 2009 38 French Academic Labs Dedicated to Liver Diseases: Aviesan Identify Targets of New Molecules For NAFLD gp130 IL-6 IL-6R
  • 11.
  • 12.
  • 13.
  • 14. The ‘Anti-inflammatory’ Pentoxifylline For Patients With Advanced Cirrhosis Marcellin et al. N Engl J Med 2008 Tenofovir vs. Adefovir For Chronic Hepatitis B Telaprevir and Peginterferon With or Without Ribavirin For Chronic Hepatitis C Hézode et al. N Engl J Med 2009 Lebrec et al. Gastroenterology 2010 Survival Without Complications Pentoxifylline (n=164) Placebo (n=171) P =0.03
  • 15.

Notes de l'éditeur

  1. Slide 76 NAFLD: Spectrum of Hepatic Pathology 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. Brunt EM. Nonalcoholic steatohepatitis. Semin Liver Dis 2004;24:3-20.
  2. Slide 76 NAFLD: Spectrum of Hepatic Pathology 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. Brunt EM. Nonalcoholic steatohepatitis. Semin Liver Dis 2004;24:3-20.
  3. On the right Residues 186–192 (shown in pink stick presentation) of the D2 domain of gp130 that are deleted in IHCAs are intimately involved in interactions with IL-6, as shown in the crystal structure of the IL-6R–IL-6–gp130 complex (PDB: 1P9M)7. IHCA deletions 173–177 and 215 (labelled in red) are also predicted to disrupt the IL-6–gp130 interface. The numbering of residues corresponds to the IL6ST complementary DNA, which has 22 additional amino-terminal residues compared with the polypeptide chain due to the peptide signal.
  4. On the right Residues 186–192 (shown in pink stick presentation) of the D2 domain of gp130 that are deleted in IHCAs are intimately involved in interactions with IL-6, as shown in the crystal structure of the IL-6R–IL-6–gp130 complex (PDB: 1P9M)7. IHCA deletions 173–177 and 215 (labelled in red) are also predicted to disrupt the IL-6–gp130 interface. The numbering of residues corresponds to the IL6ST complementary DNA, which has 22 additional amino-terminal residues compared with the polypeptide chain due to the peptide signal.