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