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
[email protected]
Roma 25 Novembre 2010
HCV Difficult to Treat Patients
Metabolic Factors
Severity of fibrosis
HCVinfected
Patient
Genetic factors
Virological
Factors
HCV Difficult to Treat Patients
Metabolic Factors
Severity of Fibrosis
HCVinfected
Patient
Genetic factors
Virological
Factors
HCV Difficult to Treat Patients
Mega-trial
Effetto medio
The promise of personalized medicine
Genetics Predict Response: IL28B Genotype C/C
Confers Higher SVR Rates
D. Ge, Nature , 2009
Rate of SVR and rs12979860 C-allele frequency in diverse ethnic groups.
DL Ge et al. Nature 461, 399-401 (2009) doi:10.1038/nature08309
SVR (%)
Genetics Predict Response: IL28B Genotype C/C
Confers Higher SVR Rates
n = 29
114 79
T/T T/C C/C
10 51 47
T/T T/C C/C
4 22 8
T/T T/C C/C
Gt 1
Gt 2/3
Gt 4
T/T
*
T/C*
C/C*
*Genotype of rs12979860 on chromosome 19 (Ge D et al. Nature. 2009;461:399-401).
Strättermayer A et al. EASL 2010.
HCV Difficult to Treat Patients
E’ la risposta all’interferone
interamente correlata al
polimorfismo genetico ?
NO
IL28b and outcome of combination
antiviral therapy with PEG-IFN + Riba
SNP
Study
Rs12979860
Ge et al.
Overall
SVR
SVR in persons with indicated
genotype (%)
% of SVR
explained by
the favorable
genotype
Homozygous
favorable
allele
Heterozygous or
homozygous
unfavorable allele
56
82
40
56
46
64
56
74
36
50
63
68
Rs8099917
Suppiah et al.
Rauch et al.
Balagopal et al. Gastroenterology 2010
HCV Difficult to Treat Patients
Metabolic Factors
Severity of fibrosis
HCVinfected
Patient
Genetic factors
Virological
Factors
Patients with virological response
(%)
HCV Difficult to Treat Patients
233 Cirrhotic pts (ITT analysis)
Di Marco V et al, personal data
HCV Difficult to Treat Patients
E’ la risposta all’interferone
interamente correlata al
polimorfismo genetico e alla
fibrosi ?
NO
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
63%
25%
0%
HCV RNA >600,000 / METAVIR F0-2
70%
29%
23%
HCV RNA >600,000 / METAVIR F3-4
37%
21%
12%
Gastroenterology 2010;139:120-9
HCV Difficult to Treat Patients
Metabolic Factors
Severity of fibrosis
HCVinfected
Patient
Genetic factors
Virological
Factors
HCV Difficult to Treat Patients
•(HEPATOLOGY 2006)
Steatosis (± visceral obesity) and IR
hyporesponsiveness to antiviral therapy.
HCV Difficult to Treat Patients
IR and SVR in G1 Chronic Hepatitis C
ROMERO-GOMEZ et al, Gastroenterology 2005
HCV Difficult to Treat Patients
Low
Vit D
SVR
Hepatology, 2010
HCV Difficult to Treat Patients
Menopause and SVR
Factors Associated with SVR
MV analysis in 442 Female Patients with CHC
Villa et al., submitted
HCV Difficult to Treat Patients
Metabolic Factors
Severity of fibrosis
Rapid Virological
Response
HCVinfectedPredictor of
as Strongest
Patient
SVR
Genetic factors
Virological
Factors
HCV Difficult to Treat Patients
RVR
Range RVR in G1 10% - 50%
HCV Difficult to Treat Patients
RVR
24 wks
PR
Baseline Predictors of RVR
in Naive Patients with G1 CHC
IL28B
Gene
Absence
of Severe
Fibrosis
RVR
Lower
BMI
LDL-COL
Vitamin D
Levels
Insulin
Resistance
Steatosis
IL-28B and RVR
IL 28
RVR
Low
Vit D
HCV Difficult to Treat Patients
IDEAL study
Differences between Peg 2-a and 2-b
• Pharmacodinamic profile
Peg 2-a
Peg 2-b
RVR 4 wk
Triple therapy
DAA
DAA
TELAPREVIR (T)
DAA
BOCEPREVIR (BOC)
DAA
LEAD-IN
HCV Difficult to Treat Patients
3 scenari clinici
• IL-28B
• LEAD IN
• TRIPLICE
RVR
LEAD-IN
RVR
PR
24 wks
Naive
IL28 TT
40%
NR
TRIPLICE
????
Naive
IL28 TC
LEAD-IN: ???
TRIPLICE
HCV Difficult to Treat Patients
TRASFERIBILITA’ RISULTATI
MEGA-TRIAL
Non tutto ciò che può essere misurato
conta, e non tutto ciò che conta può
essere misurato.
Albert Einstein
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