Monotematica AISF 2015 Modena 8-9-10 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
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..
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 < 5 5-10 12 > 12 Hepatic Venous Pressure Gradient (HVPG) (mm Hg)
Natural history of HBV-related cirrhosis. events / per year.
(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?
Only fat Fat + infl., ballooning, fibrosis 8 93 8 66 7 52
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
Importance Of Fibrosis Prediction In NAFLD N=619 Median f/u 12.6yrs P<0.001 Angulo et al. AASLD 2014
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)
The natural history of NAFLD is poorly understood No large long-term studies
Abdominal obesity Insulin resistance Hyperglycemia Increased adypolysis and release of FFA input input Dietary glucose and fructose output output input Dietary fat
steatosi = risposta adattativa precoce che limita la potenziale tossicità degli FFA
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
Ganz et al. J Transl Med (2015) 13:193
Ganz et al. J Transl Med (2015) 13:193
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 0 16 4 1 2 0 23 Stage 1 6 7 3 11 2 29 Stage 2 1 7 11 11 3 33 Stage 3 0 2 4 9 8 23 Stage 4 0 0 0 0 0 0 Total 23 20 19 33 13 108 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
Prognostic significance of DM in cirrhosis 100 % Survival 75 50 25 Without Diabetes With Diabetes P = 0.005 20 40 60 80 100 120 140 Months Bianchi, Hepatology 1994
NASH and IR: MS or Diabetes? Our Data Persico et al. Unpublished data
VF IS ASSOCIATED TO DEGREE OF LIVER FIBROSIS IN NAFLD
Similarities And Differences In Outcomes Of Cirrhosis Due To Nonalcoholic Steatohepatitis And Hepatitis C Sanyal et al, Hepatology 2006
Similarities And Differences In Outcomes Of Cirrhosis Due To Nonalcoholic Steatohepatitis And Hepatitis C Sanyal et al, Hepatology 2006
Similarities And Differences In Outcomes Of Cirrhosis Due To Nonalcoholic Steatohepatitis And Hepatitis C Sanyal et al, Hepatology 2006
Similarities And Differences In Outcomes Of Cirrhosis Due To Nonalcoholic Steatohepatitis And Hepatitis C Sanyal et al, Hepatology 2006
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
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 da quello derivante dai fattori di rischio cardiometabolico tradizionali. La malattia CV sembra condizionare l'outcome dei pazienti con NAFLD più dell'epatopatia stessa.
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 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
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 60 40 20 Stage of fibrosis Prevalence of cirrhosis 100 80 60 40 20 0 Stage 1 2 3 4 0 Yasui et al. Clin Gastro Hep 2011
Rischio relativo di HCC nel diabete
Rischio relativo di HCC nell obesità
RISK FACTORS FOR HCC IN NASH Age Advanced fibrosis Cirrhosis Diabetes mellitus Obesity Iron deposition
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.