tratamiento de la infeccion por vhc y cirrois · c-swift: grazoprevir/elbasvir + sofosbuvir in...
TRANSCRIPT
![Page 1: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/1.jpg)
TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS
Juan González García.
Jefe Sección Enfermedades Infecciosas
Coordinador de Unidad VIH
Hospital Universitario La Paz / IdiPAZ
![Page 2: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/2.jpg)
2
Conflictos de interés Juan González García
Ayudas para investigación:
Gilead, AbbVie, Janssen, BMS, MSD y ViiV
Honorarios por presentaciones y asesorías:
Gilead, AbbVie, Janssen, BMS, MSD y Roche
.
![Page 3: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/3.jpg)
3
Poblaciones con infección por VHC dificiles de tratar
CIRROSIS
Compensada
Descompensda
PACIENTES PRETRATADOS
GENOTIPO 3
INSUFOCIENCIA RENAL
COINFECCION POR VIH
![Page 4: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/4.jpg)
4
TRATAMIENTO VHC Y CIRROSIS.PERSPECTIVA GENERAL
Los pacientes con cirrosis por VHC tienen una menor probabilidad
de respuesta al tratamiento.
Razones que justifican una menor respuesta al tratamiento
Los pacientes con cirrosis compensada por VHC pueden ser tratados
con alta eficacia.
Los pacientes con cirrosis descompensada por VHC pueden ser
tratados y hay que considerar su transferencia a una Unidad
especializada de trasplante hepático.
El tratamiento en lista de espera es factible pero se asocia con una
elevada tasa de efectos adversos y hay reserva sobre su utilidad.
Los pacientes con cirrosis tratados eficazmente tienen un beneficio
clínico evidente pero no compensa totalmente el riesgo de
complicaciones
![Page 5: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/5.jpg)
5
Los pacientes con cirrosis por VHC tienen una menor probabilidad de respuesta al tratamiento.
![Page 6: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/6.jpg)
6
![Page 7: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/7.jpg)
7
![Page 8: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/8.jpg)
8
Factores
pretratamiento
asociados a
respuesta
Genotipo
Peso
Edad
(< 15% F3/4)
![Page 9: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/9.jpg)
9
41
57
0
20
40
60
80
PEGASYS® (40 kD) + COPEGUS®
RV
S(%
)
Puentes de fibrosiso cirrosis
Fibrosis leve
16 %
RVS según presencia de fibrosis avanzada
o cirrosis en genotipo 1
*Análisis por intención de tratar Hadziyannis 2004
![Page 10: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/10.jpg)
10
![Page 11: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/11.jpg)
11
HCV-TARGET: Impact of Cirrhosis and Genotype (SMV + SOF)
Nelson DR, et al. ISVHLD 2015.
SVR12 for Pts Treated With SMV + SOF ± RBVGroup N SVR (95% CI) SVR12 Estimates
Overall
Cirrhotic
Genotype
Experienced
Triple Failure
PegIFN Failure
Genotype/Cirrhosis
YesNo
1a1b
YesNo
YesNo
YesNo
1a/Cirr1b/Cirr
1a/Noncirr1b/Noncirr
715
415300
483232
439276
92623
335380
289126194106
88 (86-91)
85 (81-88)93 (9096)
85 (82-88)94 (90-97)
87 (84-90)90 (85-93)
78 (68-85)90 (87-92)
88 (84-92)88 (84-91)
81 (76-85)93 (85-96)92 (86-95)97 (90-99)
1000 5025 75
![Page 12: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/12.jpg)
12
ALLY-3: SOF + DCV for 12 Wks in Pts With GT3 HCV Infection
Of 16 pts with relapse, 11 had cirrhosis
1 of 16 relapses occurred between posttreatment Wks 4 and 12
Nelson DR, et al. Hepatology. 2015;61:1127-1135.
Treatment-Naive Pts Treatment-Experienced Pts
Overall
No cirrhosis Cirrhosis
SV
R12
(%
)
96
63
97
58
9469
105/109
20/32
73/75
11/19
32/34
9/13
100
80
60
40
20
0n/N =
![Page 13: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/13.jpg)
13
High SVR Rates Despite Multiple Negative Predictors in Genotype 1 Patients Receiving Ombitasvir/Paritaprevir/r and Dasabuvir
Reau Net al. EASL 2015. # 781
![Page 14: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/14.jpg)
14
High SVR Rates Despite Multiple Negative Predictors in Genotype 1 Patients Receiving Ombitasvir/Paritaprevir/r and Dasabuvir
Reau N et al. EASL 2015. # 781
![Page 15: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/15.jpg)
15
Razones que justifican una menor respuesta al tratamiento en pacientes con cirrosis y VHC
1. Menor tolerancia. Incremento de interrupciones de
tratamiento por efectos adversos.
2. Menor biodisponibilidad hepática de los fármacos.
3. Disfunción unmune asociada a la cirrosis
![Page 16: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/16.jpg)
16
BAJA BIODISPONIBILIDAD DE LOS ANTIVIRALES
1.Menor exposición por shunts porto-sistémico
2.Isquemia micro-vascular
![Page 17: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/17.jpg)
17
Disfunción inmune y cirrosis:Efecto dual
![Page 18: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/18.jpg)
18
Disfunción inmune y cirrosis:Efecto dual
![Page 19: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/19.jpg)
19
Contribución del hígado al sistema de vigilancia inmunológica
1.Inmunidad innata.
1. Actividad macrofágica (kuffer y cel endoteliales)
2. Linfocitos NK
3. Fuente de proteinas del sistema: complemento,citokinas, reactantes de fase aguda…
2.Inmunidad adaptativa
1. Presentación de antígenos (kuffer, cel endoteliales sinusoidales y dendríticas)
2. Linfocitos B y T residentes y en tránsito
![Page 20: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/20.jpg)
20
Cirrhosis-induced immunodeficiency
![Page 21: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/21.jpg)
21
Cirrhosis-induced immunodeficiency
![Page 22: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/22.jpg)
22
Dysfunction of CD81 T cells is mainly characterized by an impaired
proliferative capacity and the loss of antiviral effector functions such as
the secretion of IL-2 and IFN-c.
![Page 23: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/23.jpg)
23
Mechanisms involved in the failure of HBV- and HCV-specific CD8+ T-cell responses
![Page 24: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/24.jpg)
24
Los pacientes con cirrosis compensada por VHC pueden ser tratados con alta eficacia.
Ajustando duración y/o asociación de RBV en función
de
- genotipo
- la pauta seleccionada
- tratamiento previo
![Page 25: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/25.jpg)
25
SIRIUS: Impact of Tx Duration and RBV in Cirrhotic, PI-Exp’d, GT1 Pts (LDV/SOF)
12 wks of LDV/SOF + RBV
100
80
60
40
20
0
N =
24 wks of LDV/SOF
SV
R1
2 (
%)
77
9796
77
Bourlière M, et al. Lancet Infect Dis. 2015;15:397-404.
Pts with previous boceprevir, telaprevir, simeprevir, or faldaprevir
![Page 26: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/26.jpg)
26
Pooled Data: Impact of Tx Duration and RBV in Cirrhotic GT1 Pts (LDV/SOF)
Reddy KR, et al. Hepatology. 2015;62:79-86.
Pooled data (ONESTAR, ELECTRON, ELECTRON-2, 337-0113, ION-1, ION-2, SIRIUS)
No difference in SVR rate by HCV subtype
100
80
60
40
20
0Total Treatment Naive
9296 98 100
SV
R12
(%
)
118 204 133 58
96 98 97
47 45 33 36
100
Treatment Experienced
9096 98
71 159 100 22
100
12 wks of LDV/SOF12 wks of LDV/SOF + RBV
24 wks of LDV/SOF24 wks of LDV/SOF + RBV
n =
![Page 27: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/27.jpg)
27
TURQUOISE-II: Tasas de RVS12 en pacientes cirróticos GT1 naive y pretratados*
Brazo de 12 semanasBrazo de 24 semanas
3D + RBV88,6 98,595,4 100
GT 1a GT 1b
RV
S1
2,
% d
e p
aci
en
tes
124/140124/140 67/6867/68115/121115/121 51/5151/51
● En pacientes con GT1b, las tasas de RVS fueron elevadas en ambos brazos de 12 y 24 semanas
● En sujetos con GT1a, la tasa de RVS fue mayor en el brazo de 24 semanas
Poordad F et al. N Engl J Med. 2014 May 22;370(21):1973-82
* Dato Actualizado de acuerdo a la ficha técnica de Viekirax y Exviera
.
![Page 28: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/28.jpg)
28
• Los 60 pacientes eliminaron el ARN del VHC (<LLOQ) en la semana 4 de tratamiento
• Todos los pacientes completaron el tratamiento
• El 100% de los pacientes alcanzaron RVS12
% P
ati
en
ts
RVR EOTR SVR4 SVR120
20
40
60
80
100100 100
60
60
60
60 n
N60
60
60
60
100 100
% P
aci
en
tes
con
RV
S
RVR EOTR RVS4 RVS12
TURQUOISE-III: Respuesta Virológica del 100%
Feld J, et al. LO1 presented in the 15th International Symposium on Viral Hepatitis and Liver Disease, Berlin, Germany, 26-28 June 2015* Datos no incluidos en ficha técnica
VHC GT1b CPA
OBV/PTV/r + DSV
(N = 60)
![Page 29: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/29.jpg)
29
AASLD/IDSA Guidance for GT1 HCV:Treatment-Naive Pts
Population SMV + SOF LDV/SOF OMV/PTV/RTV + DSV
DCV + SOF
GT1a,no cirrhosis
12 wks ± RBV 12 wks 12 wks + RBV 12 wks
GT1a,compensated cirrhosis
24 wks ± RBV (without Q80K)
12 wks 24 wks + RBV 24 wks ± RBV
GT1b,no cirrhosis
12 wks 12 wks 12 wks 12 wks
GT1b,compensated cirrhosis
24 wks ± RBV 12 wks 12 wks 24 wks ± RBV
AASLD/IDSA. HCV guidelines.
![Page 30: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/30.jpg)
30
AASLD/IDSA Guidance for GT1 HCV:Treatment-Experienced Pts
Previous Treatment, Cirrhosis Status
SMV + SOF LDV/SOF OMV/PTV/RTV + DSV
DCV + SOF
PegIFN/RBV, no cirrhosis 12 wks 12 wks12 wks + RBV (1a)
12 wks (1b)12 wks
PegIFN/RBV, cirrhosis24 wks ± RBV
(GT1a w/out Q80K or GT1b)*
24 wks or 12 wks + RBV
24 wks + RBV (1a)12 wks (1b)
24 wks ± RBV
SOF + RBV, no cirrhosis Not recommended 12 wks + RBV Not recommended Not recommended
SOF + RBV, cirrhosis Not recommended 24 wks + RBV Not recommended Not recommended
HCV PI, + PegIFN/RBV,no cirrhosis
Not recommended 12 wks Not recommended 12 wks
HCV PI + PegIFN/RBV, cirrhosis
Not recommended24 wks or
12 wks + RBVNot recommended 24 wks ± RBV
SMV + SOF, no cirrhosis Not recommended 12 wks + RBV Not recommended 12 wks
SMV + SOF, cirrhosis Not recommended 24 wks + RBV Not recommended 24 wks ± RBV
*Not recommended if both GT1a and positive for Q80K.
AASLD/IDSA. HCV guidelines.
![Page 31: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/31.jpg)
31
EASL/ Guidance for Treatment-Naive or Treatment-Experienced with cirrhosis
![Page 32: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/32.jpg)
32
EASL/ Guidance for Treatment-Naive or Treatment-Experienced with cirrhosis
Sin RBV en 1b
Turquoise III
![Page 33: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/33.jpg)
33
AASLD/IDSA Guidance for Treatment-Naive or Treatment-Experienced GT3 Pts
PopulationRecommended Alternative
DCV + SOF SOF + RBV SOF + RBV
Naive, no cirrhosis 12 wks 12 wks + pegIFN 24 wks†
Naive, cirrhosis 24 wks ± RBV 12 wks + pegIFN 24 wks†
P/R failure, no cirrhosis 12 wks 12 wks + pegIFN Not recommended
P/R failure with cirrhosis,or SOF/RBV failure
24 wks + RBV†
12 wks + pegIFNNot recommended
Decompensated cirrhosis‡ 12 wks +
low-dose RBVUp to 48 wks*
Not recommended
*RBV dosed 1000-1200 mg/day based on weight, with consideration for pt’s CrCl and hemoglobin.†For IFN-ineligible pts. ‡Pts with GT3 HCV decompensated cirrhosis should be referred to a medical practitioner with expertise in that condition
AASLD/IDSA. HCV guidelines.
� LDV/SOF or OMV/PTV/RTV + DSV not recommended for GT3
![Page 34: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/34.jpg)
34
Partial Null
OMV/PTV/RTV + DSV + RBV x 12 wks
SV
R1
2 (
%)
OMV/PTV/RTV + DSV + RBV x 24 wks
Tx Experienced
n/N = 22/
22
18/
18
25/
25
20/
20
6/
7
3/
3
14/
14
10/
10
59/
64
52/
56
14/
15
13/
13
11/
11
10/
10
40/
50
39/
42
TURQUOISE II: Impact of Tx Duration in Cirrhotic GT1 Pts (OMV/PTV/RTV + DSV)
Poordad F, et al. N Engl J Med. 2014;370:1973-1982. Poordad F, et al. EASL 2014. Abstract O163.
GT1b GT1a
Tx Experienced
100 100 100 100 100 100100100 100
86
10092 93 93
80
93
Naive Relapser Partial Null Naive Relapser
100
80
60
40
20
0
![Page 35: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/35.jpg)
35
Los pacientes con cirrosis compensada por VHC pueden ser tratados con alta eficacia.
Otro posible abordaje
- Terapias triples libres de interferon con duración
“estándar”
¿Menor escape viral en contexto
de inmunodeficiencia?
![Page 36: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/36.jpg)
36
![Page 37: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/37.jpg)
37
C-SWIFT: GRAZOPREVIR/ELBASVIR + SOFOSBUVIR IN CIRRHOTIC AND NONCIRRHOTIC, TREATMENT-NAIVE PATIENTS WITH HEPATITIS C VIRUS GENOTYPE 1 INFECTION, FOR DURATIONS OF 4, 6 OR 8 WEEKS AND GENOTYPE 3 INFECTION FOR DURATIONS OF 8 OR 12 WEEKS
![Page 38: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/38.jpg)
38
C-SWIFT: GRAZOPREVIR/ELBASVIR + SOFOSBUVIR IN CIRRHOTIC AND NONCIRRHOTIC, TREATMENT-NAIVE PATIENTS WITH HEPATITIS C VIRUS GENOTYPE 1 INFECTION, FOR DURATIONS OF 4, 6 OR 8 WEEKS AND GENOTYPE 3 INFECTION FOR DURATIONS OF 8 OR 12 WEEKS
![Page 39: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/39.jpg)
39
Simeprevir plus daclatasvir and sofosbuvir in treatment-naïve and treatment-experienced patients with chronic hepatitis C virus genotype 1 or 4 infection and decompensated liver disease: interim results from the Phase II IMPACT study
![Page 40: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/40.jpg)
40
Los pacientes con cirrosis descompensada por VHC pueden ser tratados y hay que considerar su transferencia a una Unidad especializada de trasplante hepático.
![Page 41: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/41.jpg)
41
Daclatasvir and Sofosbuvir ± RBV in Pts With GT 1 HCV
Phase Regimen GT1 SVR, % GT1 Baseline Cirrhosis, %
III12 wks DCV + SOF +
RBV (ALLY-1)[1]
82 (advanced cirrhosis)
95 (posttransplantation)
100
III8-12 wks DCV + SOF
(ALLY-2)[2]
76 (8 wks; naive)
96 (12 wks; naive)
98 (12 wks; tx exp’d)
< 18
IIb12-24 wks DCV + SOF ±
RBV[3]
98 (12 wks; naive)
100 (24 wks; naive)
98 (24 wks; tx exp’d)
16
1. Poordad F, et al. EASL 2015. Abstract LO8. 2. Wyles DL, et al. CROI 2015. Abstract 151LB.3. Sulkowski M, et al. N Engl J Med. 2014;370:211-221.
![Page 42: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/42.jpg)
42
AASLD/IDSA Guidance for Pts With Decompensated Cirrhosis
Refer to experienced HCV practitioner (ideally liver transplant center)
Avoid IFN, TVR, BOC, SMV, OMV/PTV/RTV + DSV, or monotherapy withRBV or DAA
AASLD/IDSA. HCV guidelines.
*Initial dose of 600 mg/day, increased as tolerated.
PopulationRBV Eligible RBV Ineligible
DCV + SOF LDV/SOF DCV + SOF
GT1/412 wks +
low-dose RBV*
12 wks +
low-dose RBV*24 wks
GT1/4, SOF failureNot
recommended
24 wks +
low-dose RBV*
Not
recommended
![Page 43: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/43.jpg)
43
100
80
60
40
20
0
SV
R12
(%
)
CTP B CTP C CTP B CTP C
SOLAR-1 SOLAR-2
87 89 86 90 87 96 8572
SOLAR-1 and -2: Impact of Tx Duration in Decompensated Cirrhosis (LDV/SOF + RBV)
Error bars represent 90% CIs.
26/30
3 relapses1 death
24/27
1 relapse2 deaths
19/22
1 relapse1 death1 LTFU
18/20
1 relapse1 death
26/30
3 relapses
22/23
1 relapse
17/20
1 relapse2 deaths
13/18
1 relapse3 deaths1 w/d consent
Flamm SL, et al. AASLD 2014. Abstract 239. Manns M, et al. EASL 2015. Abstract P0774
LDV/SOF + RBV 12 wks LDV/SOF + RBV 24 wks
n/N =
![Page 44: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/44.jpg)
44
El tratamiento en lista de espera es factible pero se asocia con una elevada tasa de efectos adversos y hay reserva sobre su utilidad.
![Page 45: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/45.jpg)
45
¿Cuál es la mejor estrategia para tratar la infección por VHC en un paciente con cirrosis en lista de trasplante?
OBJETIVOS
1.Evitar la recurrencia de la hepatitis C en el
postrasplante
2.Erradicar la infección por VHC y evitar la necesidad del
trasplante al disminuir el riesgo de complicaciones
![Page 46: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/46.jpg)
46
Recomendaciones EASL 2015 en VHC y trasplante hepático
RVS > 90%
RVS > 85%
![Page 47: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/47.jpg)
47
Ombitasvir/Paritaprevir/r y Dasabuvir en el tratamiento de la recurrencia de VHC tras trasplante hepático
![Page 48: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/48.jpg)
48
Los pacientes con cirrosis tratados eficazmente tienen un beneficio clínico evidente pero no compensan completamente el riesgo de complicaciones
![Page 49: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/49.jpg)
49
Patients 337 261 192 160 124 95 79 49 31at risk
Events 0 5 11 16 20 24 25 28 30
Patients 142 76 48 35 25 14 8 6 5at risk
Events 0 0 0 0 0 1 1 1 1
Patients 337 256 183 155 121 92 74 44 27at risk
Events 0 8 21 24 27 29 31 35 35
Patients 142 76 48 35 25 14 8 6 5at risk
Events 0 0 0 0 0 1 1 1 1
SVR reduces decompensated liver disease and mortality
479 patients with advanced fibrosis treated during 1990-2003: 142 achieved SVR
Death from liver disease Liver descompensation
(%)
Año
50Events to 5 years
SVR: 4,4% (CI: 0% to 12,9%)Not SVR: 12,9% (CI: 7,7% to 18,0%)
P = ,024 (log likelihood)
Año
Events to 5 years
SVR: 0%Not SVR: 13,3% (CI: 8,4% to 18,2%)
P = ,001 (log likelihood)
0 81 2 3 4 5 6 7
(%)
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8
Not SVR
SVR
40
30
20
10
0
Veldt BJ, et al. Ann Intern Med. 2007;147(10):677-84.
![Page 50: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/50.jpg)
50
Van der Meer et al. JAMA, 2012—Vol 308
![Page 51: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/51.jpg)
51
![Page 52: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/52.jpg)
52
Cirrhosis regression in hepatitis C patients with SVR after antiviral therapy. A meta-analysis
![Page 53: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/53.jpg)
53
Non-SVR SVR
Baseline LB with F3-F4 N = 180 N = 45 P
∆ time (mo) to last TE * 56.7 (40.5-76.8) 56.5 (34.6-73.2) .558
Last TE value * 12.4 (8.1-21.8) 6.9 (5.6-9.9) <.001
≤7 kPa # 28 (15.6) 23 (51.1) <.001
7.1-9.4 kPa # 32 (17.8) 10 (22.2) .638
9.5-14.4 kPa # 40 (22.2) 5 (11.1) .145>=14.5 Kpa # 80 (44.4) 7 (15.6) .001
* median (IQR), # n (%)
TE results for patients with baseline F3-F4
![Page 54: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/54.jpg)
54
Improvement in Liver Function and Non-Invasive Esti mates of Liver Fibrosis 48 Weeks Aft er Treatment With Ombitasvir/Paritaprevir/r, Dasabuvir, and Ribavirin in HCV Genotype 1 Pati ents With Cirrhosis
Wedemeyer S., et al. EASL 2015
![Page 55: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/55.jpg)
55
Time Course of Hepatic Improvement using the HepQuant® (HQ)-SHUNT Function Test during and after Treatment with Ledipasvir/Sofosbuvir in Liver Transplant Recipients with Allograft Fibrosis or Cirrhosis and Patients with Decompensated Cirrhosis who have not undergone Transplantation
![Page 56: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/56.jpg)
56
Effect of Long-Term Viral Suppression With Sofosbuvir + Ribavirin on Hepatic Venous Pressure Gradient in HCV-Infected Patients With Cirrhosis and Portal Hypertension
![Page 57: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/57.jpg)
57
Likelihood of Experiencing Liver Morbidity Over a Lifetime Horizon
With 3D ± RBV Versus No treatment: Treatment-Naive Patients
Johnson S., et al. EASL 2015 #P0850
![Page 58: TRATAMIENTO DE LA INFECCION POR VHC Y CIRROIS · c-swift: grazoprevir/elbasvir + sofosbuvir in cirrhotic and noncirrhotic, treatment-naive patients with hepatitis c virus genotype](https://reader033.vdocumento.com/reader033/viewer/2022042023/5e7a95f6b10f2721275877d0/html5/thumbnails/58.jpg)
58
¿A qué pacientes tratar?
Dos orientaciones diferentes
• Los pacientes F3 y F4 tienen una necesidad clara de tratamiento
• Los pacientes F2 son los que más se pueden beneficiar de una mayor
eficacia y un mejor perfil de seguridad
• Los pacientes F3 y F4 tienen una necesidad clara de tratamiento
• Los pacientes F2 son los que más se pueden beneficiar de una mayor
eficacia y un mejor perfil de seguridad
EF
EC
TO
S A
DV
ER
SO
S
F0 F1 F2 F3 F4