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“Cibo e malnutrizione”
G. Svegliati BaroniSOS Epatopatie Croniche e Trapianto di Fegato
Clinica di Gastroenterologia ed EpatologiaUniversità Politecnica delle Marche, Ancona
XIII Monotematica AISF, Pisa, 17-18 ottobre 2013
Il sottoscritto dichiara di non aver avuto negli ultimi 12 mesi conflitto d’interesse in relazione a questa presentazione
e
che la presentazione non contiene discussionedi farmaci in studio o ad uso off-label
1 miliardo di persone in eccesso
ponderale, di cui 500 milioni sono
obesi.
Il settore agricolo consuma il 90%
dell’acqua disponibile a livello globale
Gli allevamenti ricoprono il 30% della
superficie terrestre e producono il 18%
di gas a effetto serra.
925 milioni di persone denutrite, 2
miliardi malnutrite.
1/3 del cibo prodotto a livello
globale è perso lungo la filiera agro-
alimentare o sprecato a livello
domestico.
Il paradosso dell’alimentazione
Malnutrition
Response of
adrenal cortex
Increase in
plasma cortisol
Muscle protein
mobilized
Increase in
plasma amino-acids
Lipoprotein Synthesis
Free fatty acid
increase
Fat deposit
in the liver
Inhibition of
Growth hormones
Growth
retardation
Odeegard & Chawla, Science 2013
Indipendent predictors of fibrosis in NAFLD and NASH
AISF Expert Committee, Dig Liv Dis 2010
QUANTITY?
QUALITY?
Tortosa, Diabetes Care 2007
Trichopoulou, N Engl J Med 2003
Fattori dietetici ambientali
• NAFLD has been induced by overfeeding of fast-food diet (Keghacias GUT 2008);
• Subjects with NAFLD:– consume more saturated fat (Musso Hepatology 2003);– consume less polyunsaturated fat (Cortez-Pinto Clin Nutr 2 006);– consume products with high glycemic index (Valtuena Am J
Clin Nutr 2006);– consume more carbohydrates (Kang Am J Gastroenterol 2006 ).
• In NASH there is a negative relationship between coffee consumption and hepatic fibrosis (Molloy Hepatology2012)
Food-derived peroxidized fatty acids may trigger hepaticinflammation: A novel hypothesis to explain steatohepat itis
Bohm et al., J Hepatol 2013
Dietary habits and their relations to insulin resistance and postprandial lipemia in NASH
• ↑↑↑↑ grassi saturi• ↑↑↑↑ colesterolo• ↓↓↓↓ grassi poliinsaturi• ↓↓↓↓ fibre• ↓↓↓↓ vitamina C ed E ( ↓↓↓↓ frutta e verdura)
Musso et al., Hepatology 2003 and Hepatology 2012
Azione diretta sulla steatosi Modulazione TG post-prandialie della sensibilità insulinica-↑↑↑↑ post-prandiale TG e VLDL-TG-↓↓↓↓ secrezione delle VLDL-↓↓↓↓ sensibilità insulinica
Adipose tissue dysfunction, including a maladaptiveadipokine response to fat ingestion, modulates liver inju ryand cardiometabolic risk in NAFLD.
Consumption of added sugars is decreasing in the United States
0
5
10
15
20
1999-2000 2001-2002 2003-2004 2005-2006 2007-2008
%
Guidelines for adults by the American Heart Associationrecommend that added sugars compose less than 5% oftotal calories (corresponding to 2.5% of calories fromfructose). Johnson et al., Circulation 2009
Welsh et al., Am J Clin Nutr 2011
Consuming fructose-sweetened, not glucose sweetened,beverages increases visceral adiposity and lipids anddecreases insulin sensitivity in overweight/obese humans
Stanhope et al., JCI 2009; Dirlewangeret al., Am J Phys iol 1999; Stanhope et al., Am J Clin Nutr 2008; Maersk, et al., Am J Clin Nutr 2012.
• Compared to glucose :– increases DNL;– promotes post-prandial hypertriglyceridemia;– induces hepatic and extra-hepatic insulin
resistance;– increases visceral adiposity.
de Wit et al., J Hepatol 2012
Increased Fructose Consumption Is Associated with Fibrosi sSeverity in Patients with Nonalcoholic Fatty Liver Diseas e
Abdelmalek et al., Hepatology 2010; Kohli et al., Hepato logy 2010; Charltonet al., AJP 2011; Ishimoto et al., Hepatology2013
The Multiple Parallel Hits Hypothesis
Tilg & Moschen, Hepatology 2010
Association Between Composition of the Human Gastro intestinalMicrobiome and Development of Fatty Liver With Chol ine Deficiency
Hildebrandt et al., Gastroenterology 2009Turnbaugh et al, Sci Transl Medicine 2009Spencer et al., Gastroenterology 2011
De Minicis et al., submitted
Gram - bacteria
Endotoxins - bacterial translocation
Portal vein
Inflammasome
LIVER
HCC
High Fat Diet
Contribution of microflora to liver damage.
De Minicis et al., Hepatology 2013
Summary of treatments
• Lifestyle advice for all patients with NAFLD;
• For patients with NASH + T2DN
– Metformin/Pioglitazone
• For patients with NASH + hypertension
– A2RBs + vitamin E
• Low threshold for statins (HCC)
• For patients with NASH only: best evidence
for vitamin E that should be considered as
first line therapy.
AGA Guidelines 2012
Estruch et al., NEJM 2013
Estruch et al., NEJM 2013
Chad, $1.23/week
Germany, $500.07/weekUnited States, $341.98/week
Italy, $260,11/week