NAFLD-cirrosi: tutto uguale?

Dimensione: px

Iniziare la visualizzazioe della pagina:

Download "NAFLD-cirrosi: tutto uguale?"

Ambrogio Berti
8 anni fa
Visualizzazioni

1 Monotematica AISF 2015 Modena ottobre NASH: malattia epatica, oncologica e cardiovascolare NAFLD-cirrosi: tutto uguale? Prof. Marcello Persico Dipartimento di Medicina e Chirurgia Medicina Interna ed Epatologia Università di Salerno

2 Prof. Marcello Persico AOU San Giovanni e Ruggi d Aragona Salerno 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 discussione di farmaci in studio o ad uso off-label..

3 The natural history of chronic liver disease Increasing liver fibrosis and neo-angiogenesis Development of HCC Chronic hepatitis Compensated cirrhosis Decompensated cirrhosis Death Variceal hemorrhage Ascites Encephalopathy Jaundice Esophageal Varices < > 12 Hepatic Venous Pressure Gradient (HVPG) (mm Hg)

4 Natural history of HBV-related cirrhosis. events / per year.

5 (Fast) Rate of progression (Slow) Female sex, young age at infection, IL28B CC? 30 years Normal liver Acute infection Modified from Lauer et al al. Chronic infection (50-80%) Chronic hepatitis Cirrhosis (20 %) Risk of HCC (1-4%/yr) 20 years Alcohol, steatosis, iron, BMI, old age, coinfections, male sex, immune deficiency, IL28B TT?

6 Only fat Fat + infl., ballooning, fibrosis

7 NAFLD si associa ad eccesso di mortalità NAFLD Reference population 129 consecutively enrolled patients diagnosed with biopsy proven NAFLD were reevaluated. Mean follow-up (SD) was 13.7 (1.3) years. Steatosis Reference population NASH Reference population

8 Importance Of Fibrosis Prediction In NAFLD N=619 Median f/u 12.6yrs P<0.001 Angulo et al. AASLD 2014

9 NAFLD probabilmente sarà nel 2020 la più frequente indicazione al trapianto di fegato nei paesi occidentali Projected relative frequencies of NASH and HCV as indications for liver transplantation (LT)

10 The natural history of NAFLD is poorly understood No large long-term studies

11 Abdominal obesity Insulin resistance Hyperglycemia Increased adypolysis and release of FFA input input Dietary glucose and fructose output output input Dietary fat

12 steatosi = risposta adattativa precoce che limita la potenziale tossicità degli FFA

13 Insulin resistance and NAFLD: Good and Bad Storers INSULIN RESISTANCE HEPATIC FATTY ACID OVERLOAD LIPOTOXICITY bad storers STEATOHEPATITIS? TG ACCUMULATION good storers SIMPLE STEATOSIS CIRRHOSIS Hepatic decompensation HCC DEATH

14 Ganz et al. J Transl Med (2015) 13:193

15 Ganz et al. J Transl Med (2015) 13:193

16 Distribution Of Histological Fibrosis At Index And Followup Liver Biopsy Baseline Fibrosis Follow-up fibrosis stage Stage 0 Stage 1 Stage 2 Stage 3 Stage 4 Total Stage Stage Stage Stage Stage Total Numbers in red (45:42% 26 progressed by 1 stage, 15 by 2 stages and 4 by 3 stages): of those having fibrosis progression 80 % were diabetic at the follow-up liver biopsy compared with 25% of nonprogressors (p = 0.005). Stuart McPherson, J Hepatol 2015

17 Prognostic significance of DM in cirrhosis 100 % Survival Without Diabetes With Diabetes P = Months Bianchi, Hepatology 1994

18 NASH and IR: MS or Diabetes? Our Data Persico et al. Unpublished data

19 VF IS ASSOCIATED TO DEGREE OF LIVER FIBROSIS IN NAFLD

20 Similarities And Differences In Outcomes Of Cirrhosis Due To Nonalcoholic Steatohepatitis And Hepatitis C Sanyal et al, Hepatology 2006

21 Similarities And Differences In Outcomes Of Cirrhosis Due To Nonalcoholic Steatohepatitis And Hepatitis C Sanyal et al, Hepatology 2006

22 Similarities And Differences In Outcomes Of Cirrhosis Due To Nonalcoholic Steatohepatitis And Hepatitis C Sanyal et al, Hepatology 2006

23 Similarities And Differences In Outcomes Of Cirrhosis Due To Nonalcoholic Steatohepatitis And Hepatitis C Sanyal et al, Hepatology 2006

24 NAFLD versus HCV. (A) Total liver-related complications. (B) Total liver-related complications adjusted by age and sex. (C) Total liver-related complications adjusted by age, sex, body mass index, and presence of diabetes. Neeraj Bhala, 2011

25 Similarities And Differences In Outcomes Of Cirrhosis Due To Nonalcoholic Steatohepatitis And Hepatitis C Sanyal et al, Hepatology 2006

Studi osservazionali che dimostrano l associazione tra NAFLD e l incidenza di morbidità e mortalità CV L'aumentato rischio CV conferito dalla NAFLD sembra indipendente

26 Studi osservazionali che dimostrano l associazione tra NAFLD e l incidenza di morbidità e mortalità CV L'aumentato rischio CV conferito dalla NAFLD sembra indipendente da quello derivante dai fattori di rischio cardiometabolico tradizionali. La malattia CV sembra condizionare l'outcome dei pazienti con NAFLD più dell'epatopatia stessa.

27 PREVALENZA dell HCC da NAFLD Marcato aumento dell incidenza di HCC nell ultimo decennio Circa metà dei casi di HCC nei paesi sviluppati si verifica oggi in pazienti senza epatite virale 0.5% in NAFLD 2.8% in NASH

Risk for HCC in NASH-cirrhosis Cleveland Clinic (2003-2007) NASH-induced

Years since cirrhosis diagnosis Yearly cumulative incidence of HCC: 2.

28 Risk for HCC in NASH-cirrhosis Cleveland Clinic ( ) NASH-induced cirrhosis, n = 195 HCV-induced cirrhosis, n =315 Proportion with HCC HCV NASH Years since cirrhosis diagnosis Yearly cumulative incidence of HCC: 2.6% in patients with NASH-cirrhosis 4.0% in patients with HCV-cirrhosis (p = 0.099) Ascha et al. Hepatology 2010

29 Cause of liver disease in the 50 patients identified with HCC

HCC in NASH often without cirrhosis Multicenter cross-sectional study of 87 patients with NASH-related HCC 100 80

30 HCC in NASH often without cirrhosis Multicenter cross-sectional study of 87 patients with NASH-related HCC Stage of fibrosis Prevalence of cirrhosis Stage Yasui et al. Clin Gastro Hep 2011

31 Rischio relativo di HCC nel diabete

32 Rischio relativo di HCC nell obesità

34 RISK FACTORS FOR HCC IN NASH Age Advanced fibrosis Cirrhosis Diabetes mellitus Obesity Iron deposition

35 Natural history of NAFLD L'aumentato rischio CV conferito dalla NAFLD sembra indipendente da quello derivante dai fattori di rischio cardiometabolico tradizionali. La malattia CV sembra condizionare l'outcome dei pazienti con NAFLD più dell'epatopatia stessa.

Documenti analoghi

I POLIMORFISMI DI IL28B NON CORRELANO CON L INCIDENZA DI HCC IN PAZIENTI CON EPATITE B IN SOPPRESSIONE VIROLOGICA

I POLIMORFISMI DI IL28B NON CORRELANO CON L INCIDENZA DI HCC IN PAZIENTI CON EPATITE B IN SOPPRESSIONE VIROLOGICA Brancaccio G., Grossi A., Marchese V., Rizzo V., Nardiello S., Gaeta G.B. Seconda Università