NASH and Type 2 Diabetes: Role of the Receptor Activator of Nuclear Factor-?B (RANK) and Its Ligand (RANKL)

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Objectives: To show that (i) expression of mRNA and proteins of the RANKL pathway (RANK, RANKL, OPG) in liver and (ii) serum concentration of RANKL/OPG proteins are correlated with the gravity of the NAFLD. Study protocol: Identify patients with different stages of NAFLD (mere steatosis, NASH, and m...

Objectives: To show that (i) expression of mRNA and proteins of the RANKL pathway (RANK, RANKL, OPG) in liver and (ii) serum concentration of RANKL/OPG proteins are correlated with the gravity of the NAFLD. Study protocol: Identify patients with different stages of NAFLD (mere steatosis, NASH, and moderate or advanced fibrosis) from the database of patients who have undergone liver biopsy in the hepatology department of the Pitié-Salpêtrière Hospital . From the hepatic tissue, the paraffin-embedded liver biopsies and the serum of these patients, study of the expression of mRNA (quantitative RtPCR) and proteins (immunohistochemistry, western blots) of the RANKL pathway (RANK, RANKL, OPG) in liver. In the serum of these patients, measure of concentration of RANKL and OPG proteins as described above. Study Type: monocentric, observational, case-control, analytical study Study duration: 18 months (time for data collection, for cellular biological experimentations and for data analysis) Patient Population: 5 groups of patients very well phenotyped and with liver biopsy (with at our disposal frozen liver tissue, paraffin-embedded liver tissue and serum for all the patients): 1) steatosis group (n=10) 2) NASH group without fibrosis (n=10) 3) moderate fibrosis (n=10) 4) advanced fibrosis (n=10) 5) healthy control group without liver disease (n=10) Comprehensive clinical and laboratory data were observed at the time of the liver biopsy and are available for all the patients.

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