INFEZIONE DA HCV - Peperosso Srlwin.peperosso.tv/public/presentazioni/Dr.ssa Menzaghi - Il...
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INFEZIONE DA HCV:
FACCIAMO IL PUNTO DOPO UN ANNO DALL’INIZIO DELLE NUOVE TERAPIE
Barbara Menzaghi
Dall’infezione alla patologia epatica
1. Adapted from Metzner KJ. Future Virol. 2006;1:377-91
Infezione
acuta1
Infezione
cronica1
15 - 50 Years
Terapia ideale per HCV: ci stiamo arrivando ?
All oral
All genotypes
High barrier
to Resistance
Optimal tolerabIlity
COst reductioN
Availability: Cirrhosis, HIV–HCV,
etc.
Short treatment
Duration
Potent Efficacyacross all patient
populations
PharmaCokinetic
(low pill burden)
Minimal
drug inTeraction
Ideal HCV treatment
GOAL = ERADICATION
0
20
40
60
80
100
IFN
6 or
12 mo
IFN+RBV
6 mo
IFN+RBV
12 mo
PEG
2a/b+RBV
12 mo
TVR+PEG
+RBV
6-12 mo
LDV/SOF
2-6 mo
62-63
19-2823
20
0
87
20112011 2013 2013
SV
R R
ate
(%
)
1 – pooled data from ION-1, ION-2, and ION-3
Jeffers L, et al. Hepatology 2004; 39: 1702-1708; Conjeevaram H, et al. Gastroenterology 2006; 131: 470-477; Muir A, et al. N Engl J Med 2004; 350: 2265-71; McHutchison J, et al. Gastroenterology 2000; 119: 1317-1323; Poordad F, et al. N Engl J Med 2011; 364: 1195-206; Bacon B, et al. N Engl J Med 2011; 364: 1207-17; Jacobson I, et al. N Engl J Med 2011; 364: 2405-16; Zeuzem S, et al. N Engl J Med 2011; 364: 2417-28; Manns M, et al. Lancet 2014; 384: 414-426; Jacobson I, et al. Lancet 2014; 384: 403-413; Lawitz E, et al. N Engl J Med 2013; 368:1878-87; Afdhal N, et al. N Engl J Med 2014; 370: 1889-98; Afdhal N, et al. N Engl J Med 2014; 370: 1483-1493; Kowdley K, et al. N Engl J Med 2014; 370: 1879-88.
SMV+PEG
+RBV
6-12 mo
63
2014
SOF+PEG
+RBV
3 mo
951
SVR Rates for Approved Therapies in HCV GT 1 TN or TE
Years are not to scale
42-61
BOC+PEG
+RBV
6-12 mo
20041998 1998
2015
J Hepatol. 2015 Apr 21. pii: S0168-8278(15)00208.
http://www.easl.eu/research/our-contributions/clinical-practice-guidelines
1) Pazienti con cirrosi in classe di Child A o B e/o con epatocarcinoma con
risposta completa a terapie resettive chirurgiche o loco-regionali non
candidabili a trapianto epatico nei quali la malattia epatica sia determinante
per la prognosi
2) Recidiva di epatite dopo trapianto di fegato con fibrosi METAVIR1 ≥2 (o
corrispondente Ishack) o fibrosante colestatica
3) Epatite cronica con gravi manifestazioni extra-epatiche HCV-correlate
(sindrome crioglobulinemica con danno d'organo, sindromi linfoproliferative
a cellule B)
4) Epatite cronica con fibrosi METAVIR ≥3 (o corrispondente Ishack)
5) In lista per trapianto di fegato con cirrosi MELD <25 e/o con HCC all'interno
dei criteri di Milano con la possibilità di una attesa in lista di almeno 2 mesi
6) Epatite cronica dopo trapianto di organo solido (non fegato) o di midollo
con fibrosi METAVIR ≥2 (o corrispondente Ishack).
7) Pazienti con epatite cronica con fibrosi METAVIR F0-F2 (o corrispondente
Ishak)
Categorie di pazienti affetti da epatite C cronica ammesse alla rimborsabilità in Italia
SVR:
Clinical
Outcomes
Prevent Decompensation
Delay Liver-Related Death
Delay/prevent HCC
Prevent Viral Recurrence After OLT
Cirrhosis regression
Slowing progression of PH
HCV Cirrhosis Natural History: can we modify it ?
Clinical
Outcomes
Cirrhosis regression
Slowing progression of PH
“Regressione” cirrosi in pazienti HCV che ottengono SVR
0
10
20
30
40
50
60
70
80
90
100
Prima di SVR Dopo SVR
Nu
mb
er
of
Pati
en
ts (
%)
Metavir
Score*
F4
F3
F2
F1
Hepatology. 2012;56:532-543.
*Median interval between pre and post-treatment liver biopsies was 79 months
«Regressione» cirrosi: in oltre il 60%
Hepatology. 2012;56:532-543.
Cumulative incidence of esophageal varices in 149 IFN ± RBV-treated patients with compensated HCV-
induced (stage 1) cirrhosis according to response to therapy
Bruno S, et al. Hepatology 2010
The impact of SVR on Esophageal Varices
Clinical
Outcomes
Prevent Decompensation
Delay Liver-Related Death
Impact of SVR on long-term outcome in 848 patients with HCV-related histologically-
proven cirrhosis (stage 1) treated with IFN MT
0 24 48 72 96 120 144 168
0
20
40
60
80
100
months
% w
ith
liv
er
co
mp
lica
tio
ns
SVR 124 119 116 108 70 41 12
no SVR 759 702 634 527 345 207 34
Patients at risk
SVR
no SVR
liver-related complications Liver-related mortality
Bruno S, et al. Hepatology 2007
(p: 0.001 by log-rank test)
(p: 0.001 by log-rank test)
0 24 48 72 96 120 144 168
0
20
40
60
80
100
months
% s
urv
iva
l to
liv
er-
rela
ted
de
ath
SVR 120 115 112 105 66 38 11
no SVR 728 680 629 541 369 234 47
Patients at risk
SVR
no SVR
The impact of SVR on long-term Outcome
Clinical
Outcomes
Delay/prevent HCC
SVR è associata ad una riduzione della mortalità correlata alle malattie del fegato e all’epatocarcinoma
van der Meer AJ, et al. JAMA. 2012; 308(24):2584-2593.
N=530 N=530
EpatocarcinomaMortalità correlata a malattia epatica
e trapianto di fegato
Clinical
Outcomes
Prevent Viral Recurrence After OLT
Post-Transplant HCV Recurrence in patients in whom HCV RNA was non detectable for 28 days prior to transplant
0 30 60 90 120 150 180 210 240 270 300 330 360 390
Days with HCV RNA Continuously TND Prior to Liver Transplant
No Recurrence (69%) Recurrence (31%)
No recurrence in 24/25 (96%) of
patients who maintained HCV RNA
TND >28 days
*Wilcoxon rank sum test.
2828
Curry AASLD 2013
NB: stop therapy at OLT !!!
OLT transforms a “suboptimal”
treatment for HCV cirrhosis in
“excellent” strategy !!
SVR:
Clinical
Outcomes
Prevent Decompensation
Delay Liver-Related Death
Delay/prevent HCC
Prevent Viral Recurrence After OLT
Cirrhosis regression
Slowing progression of PH
HCV Cirrhosis Natural History: can we modify it ?
Fino a tutt’oggi:
Valutazione SE trattare
HCV
Lieve / Assente
Malattia Epatica
Effetti collaterali
% risposta
Vantaggi ??
Trattamento “infezione”
% risposta
SI
NOEffetti collaterali
% risposta
Vantaggi ??Trattamento “infezione”
% risposta
SI
NO
Evoluta/Scompenso
FUTURO ??
Valutazione QUANDO trattare
HCV
Lieve / Assente
Costi !•% risposta
•Tollerabilità
•Paziente !!
•Eradicazione HCV
SI
NO
• ??•Malattia “evolutiva”
•% risposta
•Tollerabilità
SINO
NON evoluta / Evoluta/Scompenso
Malattia epatica
F0
F0 24
F1 27
F2 36
F3 10
F4 7
23 % 26 %
35 %
10% 7%
Evoluzione fibrosi: F0
49 %
17%
NB: Tempo 1-2 biopsia:
23 anni
NB: Tempo 1-2 biopsia:
6 anni
Curarsi subito o aspettare ?
F1
F0 0
F1 34
F2 40
F3 23
F4 11
0
32 %
37%
21%
10%
Evoluzione fibrosi: F1
31 %32% NB:
Tempo 1-2 biopsia:
> 15-20 anniNB:
Tempo 1-2 biopsia:
< 5-10 anni
Curarsi subito o aspettare ?
Evoluzione fibrosi: F2
F2
F0 0
F1 0
F2 8
F3 16
F4 35
0% 0%14 %
27 %
59%
86 %
NB: Tempo 1-2 biopsia:
> 10-15 anni
Curarsi subito o aspettare ?
HBV HCV
Trattamento antivirale
HBV-DNA (-)
HBsAg (+)
HCV-RNA (-)
antiHCV (+)
Soppresso Eradicato !
HCV and Liver Disease
Liver
Chronic HCV Infection Also Causes Extrahepatic Manifestations
Endocrine
Thyroid disease
Diabetes mellitus
Hematologic
Mixed cryoglobulinemia
Lymphoproliferative disorders
Thrombocytopenia
Renal
Membranoproliferative
glomerulonephritis
Ocular
Corneal ulcers
Sjögren syndrome
Vascular
Systemic vasculitis
Dermatologic
Lichen planus
Porphyria cutanea tarda
Musculoskeletal
Arthralgia
Myalgia
Peripheral neuropathy
Inflammatory polyarthritis
130─160 Million Chronic HCV Carriers Are at Risk of Developing Cirrhosis and/or HCC1,2
Within 20 years
1. World Health Organization. Media Centre: Hepatitis C. April 2014. http://www.who.int/mediacentre/factsheets/fs164/en/. Accessed May 20, 2014.
2. World Health Organization. Guidelines for the screening, care and treatment of persons with hepatitis C infection. April 2014. 2002.
http://www.who.int/hiv/pub/hepatitis/hepatitis-c-guidelines/en/. Accessed May 20, 2014.
Acute
infection
Spontaneous
clearance
(15%-45%)
Chronic
infection
(55%-85%)
Mild fibrosis
Moderate to
severe
fibrosis
Cirrhosis
(15%-30%)
Decompensated cirrhosis
Hepatocellular carcinoma
(2%-4% per year in cirrhosis)
HCV Host
Therapy
0
1
2
3
4
5
6
7
8
Lee et Al. J Infect Dis 2012; 206: 469-477
Is HCV more than a liver disease?Increased mortality “beyond” the liver
The REVEAL cohort study
All causes Extrahepatic Circulatory Nephritic Oesophageal Prostate Thyroiddiseases diseases Nephrotic cancer cancer cancer
Ad
just
edH
azar
dR
atio
fo
r D
eath
2.201.90-2.55
(p=0.0001)1.47
1.47-1.77(p=0.0002)
1.531.53-2.33
(p=0.0026)
2.981.43-6.22
(p=0.0032)
5.861.98-17.35(p=0.0014)
5.831.64-20.77(p=0.0065)
7.0710.73-68.35
(p=0.09)
Hazard ratio reference value:
1 for HCV negative in each disease cathegory
Factors Associated With Increased Risk Of Secondary Outcomes In Patients With HCV
McCombs, JAMA Intern Med 2014;174:204–212
Characteristic Cirrhosis HCCLiver related
Hospitalization
(n=123,988) (n=128,481)
Male gender 1.35 (1.21–1.50) 3.41 (2.39–4.88) 1.09 (1.01-1.17)
Age 1.02 (1.02–1.02) 1.07 (1.07–1.07) 0.99 (0.99-0.99)
Race White
Black
Other
1 (reference)
0.54 (0.52–0.56)
0.73 (0.70–0.76)
1 (reference)
0.73 (0.68–0.78)
0.80 (0.74–0.87)
1 (reference)
0.74 (0.72-0.76)
0.58 (0.56-0.60)
HCV genotype
1
2
3
Other
1 (reference)
0.64 (0.61–0.68)
1.24 (1.18–1.31)
0.87 (0.75–1.00)
1 (reference)
0.52 (0.46–0.58)
1.63 (1.47–1.79)
0.77 (0.57–1.04)
1 (reference)
0.80 (0.76-0.83)
1.10 (1.05-1.15)
0.89 (0.79-0.99)
Diabetes 1.38 (1.32–1.44) 1.31 (1.21–1.42) 1.19 (1.15-1.24)
Undetectable
HCV-RNA0.62 (0.54–0.73) 0.62 (0.42–0.81) 0.71 (0.63-0.80)
Cum
ulat
ive r
ates
of inc
idenc
eof
lym
phom
a(%
)
0
1
3
0 5 10 15
Years
Persistent Infection (n=2161)SVR (n=1048)
HCV Elimination Reduces The Incidence of Malignant Lymphoma
Follow-up duration (years)
2
4
0.36%
1.49%
0%0%
2.56%
0%
Log-rank test p=0.0159
Kawamura Y, et al. Am J Med 2007;120:1034-1041
Cumulative incidence of ischemic stroke, ESRD and acute coronary event in three study cohorts of diabetic
patients
Modified log rank test with death adjusted as a competing risk event.
Hsu YC et al. HEPATOLOGY 2014;59:1293-1302
Antiviral therapy for concomitant HCV
infection is associatedwith improved renal and cardiovascular outcomes
in patients with DM
ESRDISCHEMIC
STROKE
ACUTE CORONARY
EVENT
Italy
2015 ?? ?? ??
SOF..
SIM..
NOW late 2015 end 2015/2016
USA
DAA classes and subclasses: antiviral potency and resistance barrier according to HCV genotype
Drug Class Subclass1 b 1a 2 3 4
Protease inhibitors
1st Generation first wave i.e.
Telaprevir/Boceprevir
1st Generation 2nd wave i.e.
Simeprevir Paritaprevir/r
2nd Generation
Grazoprevir ABT 493
NS5a Inhibitor
1st Generation
Ledipasvir Ombitasvir Elbasvir
Daclatasvir 2nd Generation
Valpatasvir ABT 530
NN Polymerase
Inhibitors
Dasabuvir
Nucleos/tides
Polymerase
inhibitors
2nd Generation : Sofosbuvir
High Moderate Low Very low
0
10
20
30
40
50
60
70
80
90
100
1 2 3 4 5
Summary of SVR rates to IFN free regimens in HCV G1 HIV- and HIV+ Naives non Cirrhotics
SIM/SOF study Cosmos, cohorts: TRIO, TARGET
SOF/LED studies ION-1 ION-3
3D: studies PEARL SAPPHIRE
SOFO + R: SPC Sovaldi
SOF/SMV
+R
X 12-24s
SOF/DAC
+R
X 12-24s
SOF/LEDI
+R
X 12-24s
3D +R
X 12-24s
94% 99% 98% 96%
214 126 729 1380
SOFO +R
X 24s
148
68%
A
B
C
D
0
10
20
30
40
50
60
70
80
90
100
1 2 3 4
Summary of SVR rates to IFN free regimens in HCV G1 HIV- Experienced non Cirrhotics
SIM/SOF study Cosmos, cohorts: TRIO, TARGET
SOF/LED studies ION-1 ION-3
3D: studies PEARL SAPPHIRE
SOFO + R: SPC Sovaldi
SOF/SMV
+R
X 12-24s
SOF/DAC
+R
X 12-24s
SOF/LEDI
+R
X 12-24s
3D +R
X 12-24s
87% 100% 98% 96%
144 41 350 472
A
B
C
D
0
10
20
30
40
50
60
70
80
90
100
1 2 3 4
Summary of SVR rates to IFN free regimens in HCV G1 HIV- Naives Cirrhotics
SIM/SOF study Cosmos, cohorts: TRIO, TARGET
SOF/LED study meta analysis AASLD 2014
3D: studies Turquoise II
SOF/SMV
+R
X 12-24 w
SOF/LEDI
+R
X 12-24 w
3D +R
X 12-24 w
87% 98% 94%
246 161 160
A
B
C
D
SOF + R
X 124 w
11
36%
0
10
20
30
40
50
60
70
80
90
100
1 2 3
Summary of SVR rates to IFN free regimens in HCV G1 HIV- Experienced Cirrhotics
SIM/SOF study Cosmos, cohorts: TRIO, TARGET
SOF/LED study meta analysis AASLD 2014
3D: studies Turquoise II
SOF/SMV
+R
X 12-24 w
SOF/LEDI
+R
X 12-24 w
3D +R
X 12-24 w
85% 95% 90%
158 352 141
A
B
C
D
SOF/LDV ± RBV in compensated cirrhotics: SVR12 by Treatment Regimen
Bourlière et al., AASLD 2014, abstract# 82 (oral)
SVR12 by treatment regimen TotalTreatment
naïveTreatment
experienced
Overall SVR12 96% 98% 95%
Duration12 wk 95% 97% 94%
24 wk 98% 99% 98%
RegimenLDV/SOF 95% 96% 95%
LDV/SOF + RBV 97% 99% 96%
Duration/
± RBV
LDV/SOF 12 wk 92% 96% 90%
LDV/SOF + RBV 12 wk 96% 98% 96%
LDV/SOF 24 wk 98% 97% 98%
LDV/SOF + RBV 24 wk 100% 100% 100%
SVR12 %
3D: SVR12 rates in treatment-naïve andP/R-experienced cirrhotic patients with GT1a HCV
41
100
80
60
40
20
0
SVR
12
(% p
atie
nts
)
92%
HCV subtype 1a
93%93%100% 100%100%
80%
93%
5964
1415
5356
1313
1111
4050
3942
1010
ombitasvir/paritaprevir/ritonavir Summary of product characteristics. dasabuvir Summary of product characteristics. .
TURQUOISE-II
Prior partialresponse
24 wks
Prior nullresponse
Naïve
12 wks24 wks12 wks 24 wks12 wks24 wks12 wks
Prior relapse
3D:SVR12 rates in treatment-naïve andP/R-experienced cirrhotic patients with GT1b HCV
42
100
80
60
40
20
0
SVR
12
(% p
atie
nts
)
100%
Prior partialresponse
24 wks
Prior nullresponse
HCV subtype 1b
100% 100% 100%85.7%
2222
1414
1818
1010
67
2525
2020
33
100% 100%100%
1. ombitasvir/paritaprevir/ritonavir Summary of product characteristics.2. dasabuvir Summary of product characteristics.
Naïve Prior relapse
12 wks24 wks12 wks 24 wks12 wks24 wks12 wks
TURQUOISE-II
0
10
20
30
40
50
60
70
80
90
100
1 2 3 4 5 6 7 8 9 10 11 12
Summary of SVR rates in HCV G4 HIV- & HIV+
Registrative studies;RESTORE III Neutrino,PEARL –I Osinusi et al AASlD 2014, Gamal E et al AASLD 2014
PR/SIME
X 24-48 w
86% 100%
2393 55 41
A
B
C
D
PR SOFO
X 12 w
33
SOF+R
X 24 w
Naïve Exp
Non Cirrhosis
89% 44%
86 32
SOF+R
X 24 w
8
Cirrhosis
NaïveExp
SOFO/
LEDI
X 12 w
14
2D
Abbvie
X 12 w
100% 93%
PR/SIME
X 24-48 w
50
SOF+R
X 24 w
94%
2D
Abbvie
X 12 w
SOFO/
LEDI
X 12 w
SOF+R
+ LEDI
X 24 w
100% 100% 91% 80%
1081
84%
PR
DAC
X 24 w
IFN-Free Options, Gen 1a
SOF/LDV 3D SOF + SIM SOF + DCV
No cirrhosis8-12 wk
without RBV12 wk
with RBV12 wk
without RBV12 wk
without RBV
Compensated cirrhosis (CPT-A)
12 wk with RBV, or 24 wk
without RBV*
24 wk with RBV
12 wk with RBV, or 24 wk
without RBV*
12 wk with RBV, or 24 wk
without RBV*
Decompensated cirrhosis (CPT-B and CPT-C)
12 wk with RBV, or 24 wk
without RBV*
No No
12 wk with RBV, or 24 wk
without RBV*
*Patients with negative predictors of response can be treated 24 weeks with ribavirin (negative
predictors: treatment-experienced, platelet <75x103/uL)
IFN-Free Options, Gen 1b
SOF/LDV 3D SOF + SIM SOF + DCV
No cirrhosis8-12 wk
without RBV12 wk
without RBV12 wk
without RBV12 wk
without RBV
Compensated cirrhosis (CPT-A)
12 wk with RBV, or 24 wk
without RBV*
12 wk with RBV
12 wk with RBV, or 24 wk
without RBV*
12 wk with RBV, or 24 wk
without RBV*
Decompensated cirrhosis (CPT-B and CPT-C)
12 wk with RBV, or 24 wk
without RBV*
No No
12 wk with RBV, or 24 wk
without RBV*
*Patients with negative predictors of response can be treated 24 weeks with ribavirin (negative
predictors: treatment-experienced, platelet <75x103/uL)
IFN-Free Options, Gen 4
SOF/LDV 2D SOF + SIM SOF + DCV
No cirrhosis12 wk
without RBV12 wk
with RBV12 wk
without RBV12 wk
without RBV
Compensated cirrhosis (CPT-A)
12 wk with RBV, or 24 wk
without RBV*
24 wk with RBV
12 wk with RBV, or 24 wk
without RBV*
12 wk with RBV, or 24 wk
without RBV*
Decompensated cirrhosis (CPT-B and CPT-C)
12 wk with RBV, or 24 wk
without RBV*
No No
12 wk with RBV, or 24 wk
without RBV*
*Patients with negative predictors of response can be treated 24 weeks with ribavirin (negative
predictors: treatment-experienced, platelet <75x103/uL)
0
10
20
30
40
50
60
70
80
90
100
1 2 3 4 5 6 7
Summary of SVR rates in HCV G2 HIV-
Registrative studies: Fusion, Fission Positron, Valence, Lonestar,
cohorts: TRIO, TARGET
SOF+R
X 12 w
94% 81% 90%
415 282 14
A
B
C
D
PR §X 24 w
81
SOF+R
X 12 w
Naïve Exp
Non Cirrhosis
89%
SOF+R
X 12 w
87%
109
PR §X 24 w
13
SOF+R
X 12 w
62% 74%
SOF+PR
X 12 w
58
Cirrhosis
Naïve Exp
IFN-Free Options, Gen 2
SOF + RBV SOF + DCV
No cirrhosis 12 wk12 wk
without RBV
Compensated cirrhosis (CPT-A)
16-20 wk12 wk
without RBV
Decompensated cirrhosis (CPT-B and -C)
16-20 wk12 wk
with RBV
0
10
20
30
40
50
60
70
80
90
100
1 2 3 4 5 6 7
Summary of SVR rates in HCV G3 non cirrhosisHIV-& HIV+
Registrative studies: Fusion, Fission Positron, Valence, Lonestar, Ally 3, Gane et al AASLD 2014
SOF+R
X 24 w
92% 97%
146 45 75
A
B
C
D
PR SOFO
X 12 w
39
Naives
93%
SOF/DAC
X 12 w
88%
SOFO/R
X 24 w
137
PR SOFO
X 12 w
83% 97%
SOF/DAC
X 12 w
12
Experienced
SOF/LEDI
X 12 w
28
89%
0
10
20
30
40
50
60
70
80
90
100
1 2 3 4 5 6
Summary of SVR rates in HCV G3 cirrhosisHIV-& HIV+
SOF+R
X 24 w
94% 59%
16 19 13
A
B
C
D
Naives
SOF/DAC
X 12 w
68%
109
SOFO/R
X 24 w
74
PR SOFO
X 12 w
83% 69%
SOF/DAC
X 12 w
12
Experienced
22
SOF/LEDI
X 12 w
72%
Registrative studies: Fusion, Fission Positron, Valence, Lonestar, Ally 3, Gane et al AASLD 2014
IFN-Free Options, Gen 3
SOF + RBV SOF + DCV
No cirrhosis 24 wk12 wk
without RBV
Compensated cirrhosis (CPT-A)
No24 wk
with RBV
Decompensated cirrhosis (CPT-B and -C)
No24 wk
with RBV
Terapia ideale per HCV: ci stiamo arrivando ?
All oral
All genotypes
High barrier
to Resistance
Optimal tolerabIlity
COst reductioN
Availability: Cirrhosis, HIV–HCV,
etc.
Short treatment
Duration
Potent Efficacyacross all patient
populations
PharmaCokinetic
(low pill burden)
Minimal
drug inTeraction
Ideal HCV treatment
GOAL = ERADICATION
The price you pay
Drug US Price $ Estimated
Price for Italian
NHS €
Sofosbuvir 84-168.000 37.000
Daclatasvir 18.000
Simeprevir 54.000 10.000
Harvoni 94-188.000 40.000
Viekirax
Exviera
83-166.000 23.000
Il trattamento dell’epatite C: stato dell’arte
• Basi virologiche del trattamento
• Strategie di terapia
• Terapia anti HCV : AD 2015
• Terapia anti HCV: il futuro prossimo
ASTRAL studies :Sofosbuvir + Velpatasvir FDC in HCV G1, 4, 5, 6
stratified according to liver disease stage
323/
328
116/
116
34/
35
41/
41
Gilead sciences Inc: http://www.businesswire.com/news/home/20150921005402/en/
ASTRAL studies :Sofosbuvir + Velpatasvir FDC in HCV G 2 & 3 stratified
according to liver disease stage
237/
238
264/
277
Gilead sciences Inc: http://www.businesswire.com/news/home/20150921005402/en/
EFFICACY AND SAFETY OF GRAZOPREVIR/ELBASVIR +/- RBV FOR 12 OR 16 WEEKS IN PATIENTS WITH HCV G1, G4 OR G6
INFECTION WHO PREVIOUSLY FAILED PEGINTERFERON/RBV: C-EDGE TREATMENT-EXPERIENCED
Kwo P et al EASL 2015
EFFICACY OF AN 8-WEEK REGIMEN OF GRAZOPREVIR PLUS ELBASVIR WITHAND WITHOUT RIBAVIRIN IN TREATMENT-NAIVE, NONCIRRHOTIC HCV
GENOTYPE 1B INFECTION
Vierling JM et al EASL 2015