Il management del paziente difficile nelle infezioni virali croniche

Presentazione sul tema: "Il management del paziente difficile nelle infezioni virali croniche"— Transcript della presentazione:

1 Il management del paziente difficile nelle infezioni virali croniche
Definire e trattare il paziente “difficile” HCV monoinfetto Carlo Cammà Cattedra di Gastroenterologia Università di Palermo Roma 25 Novembre 2010

2 HCV Difficult to Treat Patients
HCV-infected Patient Virological Factors Genetic factors Severity of fibrosis Metabolic Factors

3 HCV Difficult to Treat Patients
HCV-infected Patient Virological Factors Genetic factors Severity of Fibrosis Metabolic Factors

4 HCV Difficult to Treat Patients The promise of personalized medicine
Effetto medio Mega-trial The promise of personalized medicine

5 Genetics Predict Response: IL28B Genotype C/C Confers Higher SVR Rates
D. Ge, Nature , 2009

6 Rate of SVR and rs12979860 C-allele frequency in diverse ethnic groups.
DL Ge et al. Nature 461, (2009) doi: /nature08309

7 Genetics Predict Response: IL28B Genotype C/C Confers Higher SVR Rates
29 114 79 10 51 47 4 22 8 T/T T/C C/C T/T T/C C/C T/T T/C C/C T/T* T/C* C/C* Gt 1 Gt 2/3 Gt 4 *Genotype of rs on chromosome 19 (Ge D et al. Nature. 2009;461: ). Strättermayer A et al. EASL 2010. 7 7

8 HCV Difficult to Treat Patients
E’ la risposta all’interferone interamente correlata al polimorfismo genetico ? NO

9 IL28b and outcome of combination antiviral therapy with PEG-IFN + Riba
SNP Study Overall SVR SVR in persons with indicated genotype (%) % of SVR explained by the favorable genotype Homozygous favorable allele Heterozygous or homozygous unfavorable allele Rs Ge et al. 56 82 40 Rs Suppiah et al. 46 36 63 Rauch et al. 64 74 50 68 Balagopal et al. Gastroenterology 2010

10 HCV Difficult to Treat Patients
HCV-infected Patient Virological Factors Genetic factors Severity of fibrosis Metabolic Factors

11 233 Cirrhotic pts (ITT analysis)
HCV Difficult to Treat Patients 233 Cirrhotic pts (ITT analysis) Patients with virological response (%) Di Marco V et al, personal data

12 HCV Difficult to Treat Patients
E’ la risposta all’interferone interamente correlata al polimorfismo genetico e alla fibrosi ? NO

13 HCV Difficult to Treat Patients
IDEAL study SVR rates IL28b Genotype CC CT TT Overall 69% 33% 27% HCV RNA ≤600,000 / METAVIR F0-2 86% 63% 52% HCV RNA ≤600,000 / METAVIR F3-4 25% 0% HCV RNA >600,000 / METAVIR F0-2 70% 29% 23% HCV RNA >600,000 / METAVIR F3-4 37% 21% 12% Come si può tradurre tutto ciò in qualcosa di clinicamente utile è evidenziato in questa tabella, con dati tratti da pazienti inclusi nel famoso studio IDEAL. La probabilità di guarire dall’epatite C con terapia antivirale (pur in presenza di un genotipo sfavorevole) varia tra 70-86% e lo 0-12% in funzione della combinazione di tre parametri: polimorfismo IL28b, presenza e severità di fibrosi e carica virale. Gastroenterology 2010;139:120-9 13

14 HCV Difficult to Treat Patients
HCV-infected Patient Virological Factors Genetic factors Severity of fibrosis Metabolic Factors

15 HCV Difficult to Treat Patients
(HEPATOLOGY 2006) Steatosis (± visceral obesity) and IR hyporesponsiveness to antiviral therapy.

16 IR and SVR in G1 Chronic Hepatitis C
HCV Difficult to Treat Patients IR and SVR in G1 Chronic Hepatitis C ROMERO-GOMEZ et al, Gastroenterology 2005 16

17 HCV Difficult to Treat Patients
LowVit D SVR Hepatology, 2010

18 HCV Difficult to Treat Patients Factors Associated with SVR
Menopause and SVR Factors Associated with SVR MV analysis in 442 Female Patients with CHC Villa et al., submitted

19 HCV Difficult to Treat Patients
HCV-infected Patient Virological Factors Genetic factors Severity of fibrosis Metabolic Factors Rapid Virological Response as Strongest Predictor of SVR

20 HCV Difficult to Treat Patients
RVR Range RVR in G1 10% - 50%

21 HCV Difficult to Treat Patients
RVR 24 wks PR

22 RVR Baseline Predictors of RVR in Naive Patients with G1 CHC
Low Baseline HCV-RNA IL28B Gene RVR Vitamin D Levels Absence of Severe Fibrosis Lower BMI LDL-COL Insulin Resistance Steatosis

23 IL-28B and RVR

24 IL 28 RVR LowVit D

25 HCV Difficult to Treat Patients
IDEAL study

26 Differences between Peg 2-a and 2-b
Pharmacodinamic profile Peg 2-a Peg 2-b RVR 4 wk Triple therapy

27 DAA

28 DAA TELAPREVIR (T)

29 DAA BOCEPREVIR (BOC)

30 DAA LEAD-IN

31 HCV Difficult to Treat Patients
3 scenari clinici IL-28B LEAD IN RVR TRIPLICE

32 PR 24 wks LEAD-IN RVR

33 Naive IL28 TT 40% NR TRIPLICE

34 ???? Naive IL28 TC LEAD-IN: ??? TRIPLICE

35 HCV Difficult to Treat Patients TRASFERIBILITA’ RISULTATI
MEGA-TRIAL

36 Non tutto ciò che può essere misurato conta, e non tutto ciò che conta può essere misurato.
Albert Einstein

37 Disclaimer Servizio scientifico offerto alla Classe Medica da MSD Italia S.r.l. Questa pubblicazione riflette i punti di vista e le esperienze dell’autore [o degli autori] e non necessariamente quelli della MSD Italia S.r.l. Ogni farmaco menzionato deve essere usato in accordo con il relativo riassunto delle caratteristiche del prodotto fornito dalla ditta produttrice. 01-13-RTG-2010-IT-4769-AV