Carlo Cammà

Cattedra di Gastroenterologia Università di Palermocarlo.camma@unipa.it

Roma 25 Novembre 2010

Il management del paziente difficile nelle infezioni virali croniche

Definire e trattare il paziente “difficile” HCV monoinfetto

HCV-infectedPatient

Virological Factors

Genetic factors

Severity of fibrosis

Metabolic Factors

HCV Difficult to Treat Patients

HCV-infectedPatient

Virological Factors

Genetic factors

Severity of Fibrosis

Metabolic Factors

HCV Difficult to Treat Patients

Effetto medioMega-trial

HCV Difficult to Treat Patients

The promise of personalized medicine

D. Ge, Nature , 2009

Genetics Predict Response: IL28B Genotype C/C Confers Higher SVR Rates

DL Ge et al. Nature 461, 399-401 (2009) doi:10.1038/nature08309

Rate of SVR and rs12979860 C-allele frequency in diverse ethnic groups.

Genetics Predict Response: IL28B Genotype C/C Confers Higher SVR Rates

SVR

(%

)

Gt 1 Gt 2/3 Gt 4

T/TT/T T/CT/C C/CC/C T/CT/C T/CT/CT/TT/T C/CC/C T/TT/T C/CC/C29 79 10 47 4 8114 51 22n =

C/C*

T/C*

T/T*

*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

SNPStudy

Overall SVR

SVR in persons with indicated genotype (%)

% of SVR explained by the favorable genotype

Homozygous favorable

allele

Heterozygous or homozygous

unfavorable allele

Rs12979860 Ge et al. 56 82 40 56Rs8099917 Suppiah et al. 46 56 36 63Rauch et al. 64 74 50 68

Balagopal et al. Gastroenterology 2010

HCV-infectedPatient

Virological Factors

Genetic factors

Severity of fibrosis

Metabolic Factors

HCV Difficult to Treat Patients

233 Cirrhotic pts (ITT analysis)

Pat

ient

s w

ith v

irolo

gica

l res

pons

e(%

)

Di Marco V et al, personal data

HCV Difficult to Treat Patients

HCV Difficult to Treat Patients

E’ la risposta all’interferone interamente correlata al

polimorfismo genetico e alla fibrosi ?

NO

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

HCV-infectedPatient

Virological Factors

Genetic factors

Severity of fibrosis

Metabolic Factors

HCV Difficult to Treat Patients

Steatosis (± visceral obesity) and IR

hyporesponsiveness to antiviral therapy.

•(HEPATOLOGY 2006)

HCV Difficult to Treat Patients

IR and SVR in G1 Chronic Hepatitis C

ROMERO-GOMEZ et al, Gastroenterology 2005

HCV Difficult to Treat Patients

SVRLowVit D

HCV Difficult to Treat Patients

Hepatology, 2010

Villa et al., submitted

Factors Associated with SVRMV analysis in 442 Female Patients with CHC

HCV Difficult to Treat Patients

Menopause and SVR

HCV-infectedPatient

Virological Factors

Genetic factors

Severity of fibrosis

Metabolic Factors

HCV Difficult to Treat Patients

Rapid Virological Response

as Strongest Predictor of SVR

RVR

HCV Difficult to Treat Patients

Range RVR in G1 10% - 50%

RVR 24 wksPR

HCV Difficult to Treat Patients

Baseline Predictors of RVR in Naive Patients with G1 CHC

RVRAbsence of Severe Fibrosis

Lower BMI

LDL-COL

Insulin Resistance Steatosis

Vitamin D Levels

IL28B Gene

IL-28B and RVR

RVRLowVit D

IL 28

IDEAL study

HCV Difficult to Treat Patients

Peg 2-a Peg 2-b

Differences between Peg 2-a and 2-b

• Pharmacodinamic profile

Triple therapy

RVR 4 wk

DAA

DAATELAPREVIR (T)

DAABOCEPREVIR (BOC)

DAA

LEAD-IN

HCV Difficult to Treat Patients

3 scenari clinici

• IL-28B

• LEAD IN RVR

• TRIPLICE

LEAD-IN RVR PR24 wks

Naive IL28 TT

NR

TRIPLICE

40%

LEAD-IN: ???TRIPLICE

Naive IL28 TC

????

TRASFERIBILITA’ RISULTATI

MEGA-TRIAL

HCV Difficult to Treat Patients

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

Albert Einstein

Disclaimer

01-13-RTG-2010-IT-4769-AV01-13-RTG-2010-IT-4769-AV

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.

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.