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COSA FARE NEL BAMBINO OBESO: NAFLD E NASH
Dott.ssa Arianna Alterio U.O. Malattie EpatoMetaboliche – Liver Research Unit
Ospedale Pediatrico Bambino Gesù
Chile: 23%
USA 31%
Taiwan 11.5%
Italy ~20-25% Canada 30%
Korea ~18%
Indonesia ~20%
India 19-28%
China 13-23%
Japan 9-30%
Brazil ~ 25%
Israel 20%
GLOBESITY
10 years F1-F2
13 years F3-F4
The degree of fibrosis, three years later, was markedly increased from the previous biopsy with the fibrosis advancing to a stage of 3 of 4 with portal, periportal, and perisinusoidal fibrosis with bridging
Patogenesi della NAFLD e della NASH
First Hits
Obesità
Insulinoresistenza
Sindrome metabolica
Dieta ipercalorica
⇑Acidi grassi liberi
*Citokine proinfiammatorie
*Disbiosi intestinale
Second Hits
Stress ossidativo
Disfunzione mitocondriale
*Citokine proinfiammatorie
*Disbiosi intestinale
NAFLD NASH
FFA + De novo lipogenesi
ACCEPTED ON 18 JUNE 2010
The I148M PNPLA3 gene variant and severity of paediatric non-alcoholic fatty liver disease
Luca Valenti, Anna Alisi, Enrico Galmozzi, Andrea Bartuli, Benedetta Del Menico, Arianna Alterio, Paola Dongiovanni, Silvia Fargion, Valerio Nobili
A sequence variation (I148M) in PNPLA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis. J Biol Chem 2009;285:6706-6715.
He S, McPhaul C, Li JZ, Garuti R, Kinch LN, Grishin NV, Cohen JC, et al.
The 148M PNPLA3 allele is a loss-of-function variant that predisposes to steatosis by decreasing triglycerides hydrolysis in hepatocytes
Equilibrium: Hepatocellular fat content
0-5%
Tg
PNPLA3 148Ile
Lipogenesis Hydrolysis of triglycerides
Lipoprotein export
ER Lipid droplets
He, J Biol Chem 2010 Zhong Li, J Clin Invest 2012 Kumari, Cell Metab 2012 Hyysalo, Diabetes 2013 Pirazzi, J Hepatol 2012
Equilibrium: Hepatocellular fat content
6%
PNPLA3 148Met
ER
Macrovescicular steatosis
PA
LPA
Mechanisms of steatosis associated with I148M PNPLA3
Obesity and insulin resistance
Excess alcohol Hepatitis C virus
PNPLA3 148I
Mild uncomplicated steatosis
PNPLA3 148M
Steatohepatitis &
fibrogenesis
Cirrhosis
Valenti, Hepatology 2012
PNPLA3 I148M variant and Progressive Liver Disease
Hepatocellular carcinoma
PNPLA3 148M/M
PNPLA3 (Hepatology 2010) LPIN – 1 (JPGN 2011) KLF – 7 (Gastroenterology 2008) SOD – 2 (J of Hepatology 2010)
FLT Fatty Liver Test
Diagnosis of Nonalcoholic Fatty Liver Disease in Children and Adolescents: Position Paper of the ESPGHAN Hepatology Committee Vajro Pietro; Lenta Selvaggia; Socha Piotr; Dhawan Anil; McKiernan Patrick; Bauman Ulrich; Durmaz Ozlem; Lacaille Florence; McLin Valerie; and Nobili Valerio
May 2012 - Volume 54 - Issue 5
CIRCONFERENZA VITA
Si misura con nastro metrico, lungo il piano orizzontale ed al termine di un’espirazione non forzata, nella zona compresa tra l’arcata costale e la spina iliaca anterior-superiore