“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