ESTADO ACTUAL DEL TRATAMIENTO DE LA HEPATITIS CRÓNICA C DR C ENRIQUE ARÚS SOLER

ESTADO ACTUAL DEL TRATAMIENTODE LA HEPATITIS CRÓNICA C

ESTADO ACTUAL DEL TRATAMIENTODE LA HEPATITIS CRÓNICA C

DR C ENRIQUE ARÚS SOLERDR C ENRIQUE ARÚS SOLER

MAGNITUDMAGNITUD

1% – 10%

185 millonespersonasinfectadas

185 millonespersonasinfectadas

3 % de la población

mundial

Importante problema de salud a nivel mundialImportante problema de salud a nivel mundial

Depende de la región geográfica y desarrollo del país

MAGNITUDMAGNITUD

1. Primera causa de enfermedad hepática1. Primera causa de enfermedad hepática

2. Primera causa de descompensación hepática2. Primera causa de descompensación hepática

3. Primera causa de carcinoma hepatocelular3. Primera causa de carcinoma hepatocelular

4. Primera causa de transplante hepático4. Primera causa de transplante hepático

Dr. E. Arús Soler

5.VHC cinco veces mas frecuente que el VIH5.VHC cinco veces mas frecuente que el VIH

EVOLUCIÓN DE LA EFICACIA DEL TRATAMIENTO DE LA HEPATITIS CRÓNICA C

INTERFERON ALFA 24 SEM

INTERFERON ALFA 48 SEM

INTERFERON MAS RIBAVIRINA 48 SEM

INTERFERON PEGILADO

INTERFERON PEGILADO MAS RIBAVIRINA

6 %

16 %

41 %

39 %

56 %

INTERFERON PEGILADO MAS RIBAVIRINA

MAS BOCEPREVIR 66 %

INTERFERON PEGILADO MAS RIBAVIRINAMAS TELAPREVIR 67 %

TRATAMIENTOS POR VÍA ORAL, LIBRES DE IFNTRATAMIENTOS POR VÍA ORAL, LIBRES DE IFN

92 -100%92 -100%

Inhibidores de la entrada del virus a la célula

Inhibidores de la entrada del virus a la célula

Inhibidores deProteasa

NS3 / NS4A

NUEVAS DROGAS EN EL TRATAMIENTONUEVAS DROGAS EN EL TRATAMIENTO

AGENTES ANTIVIRALES DE ACCIÓN DIRECTA AGENTES ANTIVIRALES DE ACCIÓN DIRECTA AADSAADS

Fármacos que inhiben directamente la replicación viral en diferentes momentos del ciclo vital del virus

Fármacos que inhiben directamente la replicación viral en diferentes momentos del ciclo vital del virus

Inhibidores de polimerasa NS5 Inhibidores de polimerasa NS5

Dr. E. Arús Soler

Dr. E. Arús Soler

TERAPEÚTICA BÁSICA APROBADAEN EL 2011

TERAPEÚTICA BÁSICA APROBADAEN EL 2011

INTERFERÓNINTERFERÓNPEGILADOPEGILADO

BOCEPREVIR

TELAPREVIR

RIBAVIRINARIBAVIRINAINHIBIDORESINHIBIDORES

DEDEPROTEASAPROTEASA

Dr. E. Arús Soler

NUEVAS ESTRATEGIAS DE TRATAMIENTO

NUEVAS ESTRATEGIAS DE TRATAMIENTO

Terapia triple y cuádruple:☻ IFN Pegylado☻ Ribavirina☻ AADs

Terapia triple y cuádruple:☻ IFN Pegylado☻ Ribavirina☻ AADs

Terapia toda por vía oral:☻ No incluye IFN

☻ Incluye varios AADs ☻ con Ribavirina ☻ sin Ribavirina

Terapia toda por vía oral:☻ No incluye IFN

☻ Incluye varios AADs ☻ con Ribavirina ☻ sin Ribavirina

Dr. E. Arús Soler

Nucleotide Polymerase Inhibitor Sofosbuvir plus Ribavirin for Hepatitis C


95pacientes

Genotipos 2 y 3Genotipo 1

GENOTIPO 2 y 3

Medicamento No. Semanas Medicamento No. Semanas Respuesta

Sofosbuvir Rib 12 semanas IFN-P 4 semanas RVS 100 %



Sofosbuvir Rib 12 semanas RVS 100 %

Sofosbuvir 12 semanas RVS 60 %

Sofosbuvir IFN-P Rib

8 semanasRVS 100 %

Gare EJ. et al N Engl J Med 2013: 368: 34-44Gare EJ. et al N Engl J Med 2013: 368: 34-44



95pacientes

Genotipos 2 y 3Genotipo 1

GENOTIPO 1

Medicamento No. Semanas Respuesta

Sofosbuvir RibPacientes naive

12 semanas RVS 84 %

Sofosbuvir RibPacientes

No Respuesta previa12 semanas

RVS 10 %

Gare EJ. N Engl J Med 2013: 368: 34-44Gare EJ. N Engl J Med 2013: 368: 34-44

Treatment of HCV with ABT-450/r–Ombitasvir and Dasabuvir with Ribavirin


ABT- 450/r Inhibidor de proteasa mas Ritonavir

Ombitasvir Inhibidor NS5A (Fosfoproteina)

Dasabuvir Inhibidor de polimerasa

ABT- 450/r Inhibidor de proteasa mas Ritonavir

Ombitasvir Inhibidor NS5A (Fosfoproteina)

Dasabuvir Inhibidor de polimerasa

ENSAYO MULTICÉNTRICO CONTROLADO ALEATORIZADODOBLE CIEGO CON PLACEBO

PACIENTES GENOTIPO 1 SIN CIRROSIS

N = 631


PACIENTES GENOTIPO 1 SIN CIRROSIS

N = 631

Jordan J. Feld, et al N Engl J Med 2014 Jordan J. Feld, et al N Engl J Med 2014



RESPUESTA VIROLÓGICA SOSTENIDA(12 SEMANAS)


96, 2 %96, 2 %

1a1a1b1b

95,3 % 98%95,3 % 98%

Jordan J. Feld, et al N Engl J Med 2014Jordan J. Feld, et al N Engl J Med 2014

ABT-450/r–Ombitasvir and Dasabuvirwith Ribavirin for Hepatitis C with Cirrhosis

ABT-450/r–Ombitasvir and Dasabuvirwith Ribavirin for Hepatitis C with Cirrhosis

ENSAYO CLÍNICO FASE 3 MULTICENTRO ALEATORIZADO ABIERTOPACIENTES GENOTIPO 1 CON CIRROSIS (CHILD-PUGH A)

N = 380

ENSAYO CLÍNICO FASE 3 MULTICENTRO ALEATORIZADO ABIERTOPACIENTES GENOTIPO 1 CON CIRROSIS (CHILD-PUGH A)

N = 380



91,8 %12 sem. de tto. 95,9 %

24 sem. de tto.

95,9 %24 sem. de tto.

Fred Poordad, et al N Engl J Med 2014Fred Poordad, et al N Engl J Med 2014

Retreatment of HCV with ABT-450/r–Ombitasvir and Dasabuvir with

Ribavirin

Retreatment of HCV with ABT-450/r–Ombitasvir and Dasabuvir with

Ribavirin


PACIENTESGENOTIPO 1 (RECAIDA, RESPONDEDORES PARCIALES Y

RESPONDEDORES NULOS)N = 394


PACIENTESGENOTIPO 1 (RECAIDA, RESPONDEDORES PARCIALES Y

RESPONDEDORES NULOS)N = 394



96,3 %96,3 %

95,3%RECAÍDA

95,3%RECAÍDA 100%

RESP.PARCIAL

100%RESP.PARCIAL 95,2%

RESP. NULA

95,2%RESP. NULA

Stefan Zeuzem, et al N Engl J Med 2014Stefan Zeuzem, et al N Engl J Med 2014

Ledipasvir and Sofosbuvir for UntreatedHCV Genotype 1 Infection


LEDIPASVIR

SOFOSBUVIR

LEDIPASVIR

SOFOSBUVIR

INHIBIDOR NS5A (FOSFOPROTEINA)

INHIBIDOR DE POLIMERASA NS5B

INHIBIDOR NS5A (FOSFOPROTEINA)

INHIBIDOR DE POLIMERASA NS5B

ENSAYO CLÍNICO FASE 3 MULTICENTRO ALEATORIZADO ABIERTOPACIENTES GENOTIPO 1 NO TRATADOS

(HEPATITIS CRÓNICA Y CIRROSIS) N = 865

ENSAYO CLÍNICO FASE 3 MULTICENTRO ALEATORIZADO ABIERTOPACIENTES GENOTIPO 1 NO TRATADOS

(HEPATITIS CRÓNICA Y CIRROSIS) N = 865

Nezam Afdhal, et al N Engl J Med 2014Nezam Afdhal, et al N Engl J Med 2014





LEDISPAVIR MAS SOFOSBUVIR 12 SEM. 99%

LEDISPAVIR MAS SOFOSBUVIR MAS RIBAVIRINA 12 SEM. 97%








Ledipasvir and Sofosbuvir for PreviouslyTreated HCV Genotype 1 Infection

Ledipasvir and Sofosbuvir for PreviouslyTreated HCV Genotype 1 Infection

ENSAYO CLÍNICO MULTICENTRO ALEATORIZADO ABIERTOPACIENTES GENOTIPO 1 PREVIAMENTE TRATADOS

(HEPATITIS CRÓNICA Y CIRROSIS)N = 440

ENSAYO CLÍNICO MULTICENTRO ALEATORIZADO ABIERTOPACIENTES GENOTIPO 1 PREVIAMENTE TRATADOS

(HEPATITIS CRÓNICA Y CIRROSIS)N = 440












Ledipasvir and Sofosbuvir for 8 or 12 Weeksfor Chronic HCV without Cirrhosis

Ledipasvir and Sofosbuvir for 8 or 12 Weeksfor Chronic HCV without Cirrhosis

ENSAYO CLÍNICO FASE 3 MULTICENTRO ALEATORIZADO ABIERTOPACIENTES GENOTIPO 1. NO TRATADOS. SIN CIRROSIS

N = 831

ENSAYO CLÍNICO FASE 3 MULTICENTRO ALEATORIZADO ABIERTOPACIENTES GENOTIPO 1. NO TRATADOS. SIN CIRROSIS

N = 831

LEDISPAVIR MAS SOFOSBUVIR 8 SEM

LEDISPAVIR MAS SOFOSBUVIR MAS RIBAVIRINA 8 SEM.



LEDISPAVIR MAS SOFOSBUVIR MAS RIBAVIRINA 8 SEM.


94%94%

93% 93%

95% 95%



Kris V. Kowdley,Kris V. Kowdley, et al N Engl J Med 2014 et al N Engl J Med 2014

Daclatasvir plus Sofosbuvir for PreviouslyTreated or Untreated Chronic HCV Infection


ENSAYO CLINICO MULTICENTRO, ALEATORIZADO, ABIERTOPACIENTES CON HEPATITIS CRÓNICA NO TRATADOS Y

PREVIAMENTE TRATADOSN = 211

ENSAYO CLINICO MULTICENTRO, ALEATORIZADO, ABIERTOPACIENTES CON HEPATITIS CRÓNICA NO TRATADOS Y

PREVIAMENTE TRATADOSN = 211

DACLATASVIR INHIBIDOR DE POLIMERASA NS5A

SOFOSBUVIR INHIBIDOR DE POLIMERASA NS5B

DACLATASVIR INHIBIDOR DE POLIMERASA NS5A

SOFOSBUVIR INHIBIDOR DE POLIMERASA NS5B

Sulkowski MS, et alSulkowski MS, et al N Engl J Med 2014;370:211-21.N Engl J Med 2014;370:211-21.





GENOTIPO 1GENOTIPO 1

PACIENTES NO TRATADOS PREVIAMENTE

DCL, SOF Y RIB DCL Y SOF

PACIENTES NO TRATADOS PREVIAMENTE

DCL, SOF Y RIB DCL Y SOF

94% 98% 98% 94% 98% 98%

PACIENTES TRATADOS PREVIAMENTEIFN-P, RIB, BOC o TEL

PACIENTES TRATADOS PREVIAMENTEIFN-P, RIB, BOC o TEL

GENOTIPO 2GENOTIPO 2 GENOTIPO 3 GENOTIPO 3

92% 89%92% 89%

Sulkowski MS, et alSulkowski MS, et alN Engl J Med 2014;370:211-21N Engl J Med 2014;370:211-21

Recommendations for Testing, Managing,and Treating Hepatitis C

2014

Recommendations for Testing, Managing,and Treating Hepatitis C

2014

Classification Description

Class I Conditions for which there is evidence and/or general agreement that a given diagnostic evaluation, procedure, or treatment is beneficial, useful, and effective

Class II Conditions for which there is conflicting evidence and/or a divergence of opinion aboutthe usefulness and efficacy of a diagnostic evaluation, procedure, or treatment

Class IIa Weight of evidence and/or opinion is in favor of usefulness and efficacy

Class IIb Usefulness and efficacy are less well established by evidence and/or opinion

Class III Conditions for which there is evidence and/or general agreement that a diagnostic evaluation, procedure, or treatment is not useful and effective or if it in some cases may be harmful

Level of Evidence Description

Level A Data derived from multiple randomized clinical trials or meta-analysesLevel B Data derived from a single randomized trial, or nonrandomized studiesLevel C Consensus opinion of experts, case studies, or standard

Classification Description

Class I Conditions for which there is evidence and/or general agreement that a given diagnostic evaluation, procedure, or treatment is beneficial, useful, and effective

Class II Conditions for which there is conflicting evidence and/or a divergence of opinion aboutthe usefulness and efficacy of a diagnostic evaluation, procedure, or treatment

Class IIa Weight of evidence and/or opinion is in favor of usefulness and efficacy

Class IIb Usefulness and efficacy are less well established by evidence and/or opinion

Class III Conditions for which there is evidence and/or general agreement that a diagnostic evaluation, procedure, or treatment is not useful and effective or if it in some cases may be harmful

Level of Evidence Description

Level A Data derived from multiple randomized clinical trials or meta-analysesLevel B Data derived from a single randomized trial, or nonrandomized studiesLevel C Consensus opinion of experts, case studies, or standard

Grading System Used to Rate the Level of the Evidence and Strength of theRecommendation

Grading System Used to Rate the Level of the Evidence and Strength of theRecommendation

Recommended regimen for treatment-naive patients with HCV genotype 1 who are eligible to receive IFN.

Daily sofosbuvir (400 mg) and weight-based RBV

(1000 mg [<75 kg] to 1200 mg [≥75 kg]) plus weekly PEG for 12 weeks

Class I, Level A

Recommended regimen for treatment-naive patients with HCV genotype 1 who are eligible to receive IFN.

Daily sofosbuvir (400 mg) and weight-based RBV

(1000 mg [<75 kg] to 1200 mg [≥75 kg]) plus weekly PEG for 12 weeks

Class I, Level A

Recommended regimen for treatment-naive patients with HCV genotype 1 who are not eligible to receive IFN

.

Recommended regimen for treatment-naive patients with HCV genotype 1 who are not eligible to receive IFN

.

Daily sofosbuvir (400 mg) plus simeprevir (150 mg), with or without

weight-based RBV (1000 mg [<75

kg] to 1200 mg [≥75 kg) for 12 weeks

Daily sofosbuvir (400 mg) plus simeprevir (150 mg), with or without

weight-based RBV (1000 mg [<75

kg] to 1200 mg [≥75 kg) for 12 weeks

Class I, Level AClass I, Level A

Alternative regimens for treatment- naive patients with HCV genotype 1 who are eligible to receive IFN.

Alternative regimens for treatment- naive patients with HCV genotype 1 who are eligible to receive IFN.

Daily simeprevir (150 mg) for 12 weeks and weight-based RBV (1000 mg [<75

kg] to 1200 mg [≥75 kg]) plus weekly PEG for 24 weeks

Daily simeprevir (150 mg) for 12 weeks and weight-based RBV (1000 mg [<75

kg] to 1200 mg [≥75 kg]) plus weekly PEG for 24 weeks

Class IIa, Level AClass IIa, Level A

Alternative regimens for treatment-naive patients with HCV genotype 1 who are not eligible to receive IFN

Alternative regimens for treatment-naive patients with HCV genotype 1 who are not eligible to receive IFN

Daily sofosbuvir (400 mg) and weight-based RBV(1000 mg [<75 kg] to 1200 mg

[≥75 kg]) for 24 weeks

Daily sofosbuvir (400 mg) and weight-based RBV(1000 mg [<75 kg] to 1200 mg

[≥75 kg]) for 24 weeks

Class IIb, Level BClass IIb, Level B

The following regimens are NOT recommended for treatment-naive patients with HCV genotype 1.

The following regimens are NOT recommended for treatment-naive patients with HCV genotype 1.

PEG/RBV with or without telaprevir or boceprevir for 24 to 48 weeksPEG/RBV with or without telaprevir or boceprevir for 24 to 48 weeks

Class IIb, Level AClass IIb, Level A

Monotherapy with PEG, RBV, or a DAAMonotherapy with PEG, RBV, or a DAA

Class III, Level AClass III, Level A

Recommended regimen for treatment-naive patients with HCV genotype 2, regardless of eligibility for IFN therapy

Recommended regimen for treatment-naive patients with HCV genotype 2, regardless of eligibility for IFN therapy

Daily sofosbuvir (400 mg) and weight-based RBV (1000 mg

[<75 kg] to 1200 mg [≥75 kg])for 12 weeks

Daily sofosbuvir (400 mg) and weight-based RBV (1000 mg

[<75 kg] to 1200 mg [≥75 kg])for 12 weeks

Class I, Level AClass I, Level A

Recommended regimen for treatment-naive patients with HCV genotype 3 regardless of eligibility for IFN therapy

Recommended regimen for treatment-naive patients with HCV genotype 3 regardless of eligibility for IFN therapy

Daily sofosbuvir (400 mg) and weight-based RBV (1000 mg [<75 kg]

to 1200 mg [≥75 kg]) for 24 weeks

Daily sofosbuvir (400 mg) and weight-based RBV (1000 mg [<75 kg]

to 1200 mg [≥75 kg]) for 24 weeks

Class I, Level BClass I, Level B

The following regimens are NOT recommended for treatment-naive patients with HCV genotype 2 and 3

The following regimens are NOT recommended for treatment-naive patients with HCV genotype 2 and 3

PEG/RBV for 24 or 48 weeklyPEG/RBV for 24 or 48 weekly

Class I, Level BClass I, Level B

Monotherapy with PEG, RBV, or a DAAMonotherapy with PEG, RBV, or a DAA


Telaprevir-, boceprevir-, or simeprevir-based regimensTelaprevir-, boceprevir-, or simeprevir-based regimens


RESPUESTA VIROLÓGICA DURANTE ELTRATAMIENTO

RESPUESTA VIROLÓGICA RNA-VHC NEGATIVO A LA SEMANA 4 DE TTO. RÁPIDA ( RVR).

RESPUESTA VIROLÓGICA REDUCCIÓN DE > 2 LOG RNA-VHC A LA TEMPRANA (RVT) SEMANA 12 DE TTO. (RVT PARCIAL)

RNA-VHC NEGATIVO A LA SEMANA 12 DE TTO. (RVT COMPLETA)

RESPUESTA AL FINAL RNA-VHC NEGATIVO A LA SEMANA 24 O 48DEL TRATAMIENTO (RFT) DE TTO.

RESPUESTA VIROLÓGICA RNA-VHC NEGATIVO 24 SEMANAS DESPUÉSSOSTENIDA (RVS) DE TERMINADO EL TTO.

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ESTADO ACTUAL DEL TRATAMIENTO DE LA HEPATITIS CRÓNICA C DR C ENRIQUE ARÚS SOLER