This document summarizes information about non-alcoholic fatty liver disease (NAFLD). It begins by defining NAFLD as a spectrum of liver disease ranging from simple fatty liver or steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. It then discusses the global prevalence of NAFLD, key risk factors like obesity, diabetes, genetic factors, and demographic information. Mortality risks associated with NAFLD are also summarized, showing increased risks of death from liver-related causes and all-cause mortality correlated with fibrosis stage. The document concludes by noting NAFLD is now considered a systemic disease with potential extrahepatic manifestations affecting other organ systems.

1. NAFLD:unapproccioclinico
multidisciplinare
P.O. Orvieto, 18 novembre 2019
h 14:30, aula convegni p.-2
«Dimensione del problema: epidemiologia,
fattori genetici ed ambientali»
G. RALLI, Specialista in Medicina Interna
Medicina Generale P.O. Orvieto

2. What is NAFLD?
Risk Factors
Mortality
«A Sistemic Disease»
TO DO LIST

3. What is NAFLD?
Risk Factors
Mortality
«A Sistemic Disease»
TO DO LIST

4. What is
Non Alcoholic Fatty Liver Disease??
A Spectrum of Liver Disease
«Fatty Liver or Steatosis»

5. What is
Non Alcoholic Fatty Liver Disease??
A Spectrum of Liver Disease
Steatosis NASH Cirrhosis
«Fatty Liver or Steatosis»
Fat accumulates
in the liver
Fat plus
inflammation
and scarring
Scar tissue
replaces liver
cells
(Steatohepatitis)

6. Global Prevalence of NAFLD
In 2018, it is estimated that about 25% of the world population has NAFLD
Younossi et al. Hepatology 2019

7. NAFLD: Obesity
0
10
20
30
40
50
60
70
80
Obesity Obesity /
bariatric surgery
NAFLD lean
NAFLD%
0
10
20
30
40
50
60
70
25-30 30-35 40-45 45-50
NAFLD%
BMI (KG/M2)
 Obesity independently led to 4-6 fold increased risk for developing NAFLD
 Visceral obesity predicts significant fibrosis (F3-F4 Metavir score)
Lazo et Clark Semin Liver Dis 2008
Li et al Obes Rev 20016
54,2%
70,1%
15,3%
16,8%

8. NAFLD in Diabetes
0
10
20
30
40
50
60
70
80
90
T2DM T2DM / Obesity T2DM / MetS
NAFLD%
 The prevalence of NASH in patients NAFLD/T2DM is estimated at 78%
 The frequency of HCC is increased to 4-6 fold in the T2DM
Seto et al j Gastroenterol 2017
Li et al Obes Rev 20016
0
10
20
30
40
50
60
70
80
90
NAFLD / T2DM NAFLD / No T2DM
%
NASH F3-F4
51%
83% 81%
Prevalence NASH/Fibrosis

9. NAFLD role Gender and Age
 Significant prevalence sex male (57,3%), peak was in aged 60-79 years
 Age < 18 years old prevalence 4-6%, M/F ratio (2:1)
Alexander et al. BMC Medicine 2018
0
5
10
15
20
25
30
35
40
45
50
< 18 18-29 30-39 40-49 50-59 60-69 70-79 80-89 > 90
%
Health Search Data Base, Italy (N = 24,027)
Male Female

10. NAFLD: Ethnicity and Race
Browning et al. Hepatology 2004
0 10 20 30 40 50
Blacks
Whites
Hispanic
Pooled prevalence
24%
33%
45%
26%
NAFLD %
Prevalence of Hepatic Steatosis in an Urban Population in the
United States: Impact of Ethnicity (Dallas Heart Study)

11. What is NAFLD?
Risk Factors
Mortality
«A Sistematic Disease»
TO DO LIST

12. Risk Factors for NAFLD
Tarquini et al.G It Diabetol Metab 2012
Pathological conditions most frequently associated with NAFLD
Obesity
50-90%
Hypertension
22%
Diabetes
28-55% Dyslipidemia
22-92%
INSULIN-
RESISTANT
Microbiota
Genetic
Polimorphisms
NAFLD

13. Genetic Polimorphisms
Miyaaki et al. Clin J Gastroenterol 2017

14. C>GAAG TCA AT
PNPLA3 polimorphism I148M C>G
 CG, GG (Genetic Variants)
 CC (Wild type)  Isoleucina
 Methionina
CODON 148
Chromosome 22 I148Mc
 Incresed with feeding
 Expressede high level in fat and liver
 Nonspecific lipase activity
ADIPONUTRIN

15. Dongiovanni et al. WJG 2013
PNPLA3:
Mechanism of Hepatic Fat Accumulation

16. PNPLA3 and NAFLD severity
0
1
2
3
4
5
6
7
8
9
African-Americans Hispanics
HEPATICTGCONTENENT(%)
II IM MM
 PNPLA3 genetic variant has been associated with increased TG accumulation, fibrosis,
and predisposes to hepatocellular carcinoma
Romeo et al. Nat Genet 2008
Valenti et al. Plot One 2013

17. What is NAFLD?
Risk Factors
Mortality
«A Sistemic Disease»
TO DO LIST

18. NAFLD: All-Cause Mortality
Cohort study of pts in Sweden with NAFLD (N = 229) followed for
a mean of 26.4 ± 5.6 yrs
Ekstedt et al . Hepatology 2015
Reference population
Pts fibrosis stage F0-F2
Pts fibrosis stage F3-F4

19. Ekstedt et al. Hepatology 2015
NAFLD: Mortality Liver-related
1,60x 2,52x 3,48x
6,40x
9,57x
16,69x
42.30x
0
10
20
30
40
50
60
F1 F2 F3 F4
MORTALITYRATERATIO
FIBROSIS STAGE
Overall Liver-related
Cohort study of pts in Sweden with NAFLD (N = 229) followed for
a mean of 26.4 ± 5.6 yrs
Cause liver-related death:
 HCC (60%)
 Cirrhosis (45%)
 Others (5%)

20. New Liver Transplant Waitlist
Wong et al. Gastroenterology 2015
Data from United Network for Organ Sharing and Organ Procurement and
Transplantation Network registry since 2004 to 2013
NASH Is the Second Leading Etiology of Liver Disease Among Adults
Awaiting Liver Transplantation in the United States

21. What is NAFLD?
Risk Factors
Mortality
«A Sistemic Disease»
TO DO LIST

22. «A Sistematic disease»
Younussi et al. Hepatology 2019 «Extrahepatic» manifestations of NAFLD
Renal
 Chronic Kidney disease
 Hyperuricemia
Cardiac
 Coronary Artery disease
 Left Ventricular Disfuction
Vascular
 ↑Intima-media Thickness
Malignancy
 Colon Rectal, Breast
Biliary
 Gallstone disease (?)
Gynecologic
 Polycystic Ovary Syndrome
Respiratory
 Obstructive Sleep Apnea
Muscolar
 Osteoarthritis (?)
Targher et al. G It Diabetol Metab 2012
Nobili et al. Thorax 2015
Kwak et al. Digestive and Liver Disease 2019

23. Thanks for your attention!!