“caso&clínico&de&vhc”&...2017/09/06 · departamento*de*gastroenterología *...
TRANSCRIPT
Ignacio García Juárez Departamento de Gastroenterología
26 de Agosto del 2017
Departamento de Gastroenterología Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
“Caso Clínico de VHC”
37 años THO Oct/2013
MELD 30 Tacrolimus HCV GT1b Peso 65 kg
6 meses complicaciones
Caso en la Vida Real
A los 6 meses complicaciones: con colestasis
Ictericia generalizada
• Leu (109 /L) 3.2
• Hemoglobina (g/dL) 12.8
• Pla (109 /L) 140
• ALT (UI/L) 300
• AST (UI/L) 400
• FA(UI/L) 200
• BT (mg/dL) 22
• GGT (UI/mL) 250
• INR 1.0
• RNA VHC ( UI/mL) 2,000,000
Ultrasonido – Normal.
Caso Clínico
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simbolo masculina
CPRE
Biopsia Hepática
METAVIR A2 F0
PEG-Inf + Ribavirina + Boceprevir
TC de abdomen
Al segundo día de inicio del tratamiento presentó dolor abdominal
Peg-IFN y RBV
Mg/
dl
UI/L
UI/m
L (m
illon
es)
Suspendió RBV Peg-IFN 50mcg/sem
Suspendió RBV Peg-IFN 50mcg/sem
Suspendió RBV Peg-IFN 50mcg/sem
AST ALT
Pregunta:
Cuanto tiempo después del trasplante hepático se puede utilizar el esquema AAD con seguridad:
a. Al año del THO
b. Después de 3 meses
c. Inmediatamente
Sofosbuvir/Ledipasvir/rbv (FibroScan F2) Diciembre.2016
107
106
105
104
103
102
101
Log
UI/m
L
CV indetectable
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SOLAR – 1: SVR 12 en THO en tto con LDV/SOF + RBV
Los scores de MELD mejoraron desde la línea de base en el seguimiento a la semana 4 en 15/48 pacientes con CPA y en 8/41 con CHP
Reddy RT, et al. AASLD 2014. Abstract 8.
12 Semanas 24 Semanas
53/55 55/56 25/26 24/25 22/26 15/18 3/15 2/3
96 96 96 98 85 83 60 67
100
80
60
40
20
0
RVS
12
(% d
e pa
cien
tes)
97,1%
33/34
3D + RBV 24 semanas
33/34
97,1% RVS12 del 97,1%
Razones por las que no se alcanzó la RVS
Un paciente sufrió recaída virológica (día 3 posterior al tratamiento)
Al momento de la recidiva, este paciente presentaba variantes de aminoácido R155K en proteasa NS3, M28T+Q30R en NS5A, y G554S en NS5B, ninguno de los cuales se encontraban presentes en el inicio
RVS12 del 97,1%
Kwo PY, et al.N Engl J Med.2014;372(25):2375-2382.
CORAL – 1: GT-1 postrasplante
Durante Tx (Semana 1–4)
Pre-Treatmento
TAC
Con
cent
raci
ón (n
g/m
L) 12
10
8
6
4
2
0
200
150
100
50 C
yA C
once
ntra
ción
(ng/
mL)
Pre-Treatmento Durante el Tx
Ajuste de Tacrolimus durante el tratamiento de 3D
Ajuste de Ciclosporina A durante el tratamiento de 3D
CORAL-I: Recurrencia de VHC en THO. Concentraciones de Tac y CyA antes y después del tratamiento de 3D
0.5mg cada 7 días 1/5 de la dosis basal/día
Badri P, et al. Hepatology 2014; 60(Suppl):1149A.
ALLY-1: Resultados Sofos/Dacla + RBV
Poordad F, et al. EASL 2015. Abstract LO8.
Genotipo
100
80
60
40
20
0
SVR
12 (%
)
Global
CH avanzada
Post-tho
50/60 50/53
83 94
n/N =
4 6
CH avanzada
4/ 4
100
26/34
76
1a 1b 2 3 4 6 1a 1b 2 3
11/ 11
100
4/ 5
80
5/ 6
83
0/ 0
30/31
97
9/ 10
90
0/ 0
10/ 11
91
0/ 0
1/ 1
100
Post-trasplante
Child-Pugh
CH avanzada
11/12
92
A B C
30/ 32
94
9/ 16
56
Respuesta al tratamiento
8 pacientes con recaída (109/121) No recaídas en sem. 4 y 12 post tto.
Sofosbuvir/simeprevir con o sin RBV (G 1)
Hepatology.2015
Correspondence
n engl j med 375;21 nejm.org November 24, 2016
and NS5B was performed for all recipients at baseline.
Figure 1 shows HCV RNA levels from day −1 to the end of study. The rate of sustained viro-logic response for the 4-week course was 88% (Table S2 in the Supplementary Appendix). One patient had a relapse after the 4 weeks, but a sustained virologic response was achieved after retreatment with 12 weeks of ledipasvir–sofos-buvir per the study protocol, leading to an over-all cure in 15 of the 16 patients (94%). This patient had three NS5A resistance-associated substitutions at study enrollment. One patient discontinued treatment after the creatinine clearance fell below a predefined threshold of 30 ml per minute on day 5. Overall, 88% of the patients had adverse events after liver transplan-tation, and 31% had serious adverse events (Ta-bles S3 and S4 in the Supplementary Appendix). No patient discontinued treatment owing to an adverse event, had graft loss, or died.
In this trial of preemptive therapy in HCV-positive patients undergoing liver transplantation, a 4-week course of perioperative ledipasvir– sofosbuvir led to a high rate of sustained viro-logic response, suggesting that it may be an ef-fective approach for preventing HCV recurrence. The only patient with a virologic relapse had NS5A resistance at baseline and had a response to an additional 12 weeks of therapy, suggesting that baseline resistance testing may guide the need for standard courses of therapy. This new perioperative approach needs to be tested in dif-ferent populations, such as repeat or combined organ recipients and patients with previous DAA treatment failures, and in those with advanced renal failure (other DAAs). In addition, there may be an opportunity to test modifications of this approach in liver or other solid organ recipients being offered HCV-positive organs as a way to increase the donor pool and number of trans-plants.
Figure 1. Hepatitis C Virus (HCV) RNA Levels from Day –1 to Post-Treatment Week 12.
The black curves represent the patients who had a sustained virologic response 12 weeks after the end of the 4-week treatment. The green curve represents a patient who had a relapse after initial treatment and had a sus-tained virologic response after 12 weeks of retreatment. The orange curve represents a patient who discontinued treatment on day 5 of the study owing to predefined stopping criteria. LLOQ denotes the lower limit of quantifi-cation.
≤1.15(LLOQ)
Study Day Week after Treatmentor of Retreatment
HCV
RN
A (lo
g 10 IU
/ml)
3
1
2
6
4
5
7
8
014 21 28 1 121−1 3 5 7
Day beforeTransplantation
The New England Journal of Medicine Downloaded from nejm.org on August 22, 2017. For personal use only. No other uses without permission.
Copyright © 2016 Massachusetts Medical Society. All rights reserved.
RN
A H
CV
(log
10 U
I/ml
Día previo al Trasplante
Día del estudio Semana después del Tratamiento o Retratamiento
(LIDC)
Niveles de RNA del Virus de Hepatitis C (HCV) desde el día -1 hasta la semana 12 pos-tratamiento.
Futuro del Tratamiento del VHC
New England Journal Medicine 2016
Conclusiones
Los AAD tienen ALTA eficacia y seguridad La Inmunosupresión no contraindica el uso de los AAD Puede indicarse inmediatamente después del THO