Post on 23-Jan-2016
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
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 IFN-P 8 semanas RVS 100 %
Sofosbuvir Rib 12 semanas IFN-P 12 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
Nucleotide Polymerase Inhibitor Sofosbuvir plus Ribavirin for Hepatitis C
Nucleotide Polymerase Inhibitor Sofosbuvir plus Ribavirin for Hepatitis C
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
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
ENSAYO MULTICÉNTRICO CONTROLADO ALEATORIZADODOBLE CIEGO CON PLACEBO
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
Treatment of HCV with ABT-450/r–Ombitasvir and Dasabuvir with Ribavirin
Treatment of HCV with ABT-450/r–Ombitasvir and Dasabuvir with Ribavirin
RESPUESTA VIROLÓGICA SOSTENIDA(12 SEMANAS)
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
RESPUESTA VIROLÓGICA SOSTENIDA(12 SEMANAS)
RESPUESTA VIROLÓGICA SOSTENIDA(12 SEMANAS)
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
ENSAYO MULTICÉNTRICO CONTROLADO ALEATORIZADODOBLE CIEGO CON PLACEBO
PACIENTESGENOTIPO 1 (RECAIDA, RESPONDEDORES PARCIALES Y
RESPONDEDORES NULOS)N = 394
ENSAYO MULTICÉNTRICO CONTROLADO ALEATORIZADODOBLE CIEGO CON PLACEBO
PACIENTESGENOTIPO 1 (RECAIDA, RESPONDEDORES PARCIALES Y
RESPONDEDORES NULOS)N = 394
RESPUESTA VIROLÓGICA SOSTENIDA(12 SEMANAS)
RESPUESTA VIROLÓGICA SOSTENIDA(12 SEMANAS)
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 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
Ledipasvir and Sofosbuvir for UntreatedHCV Genotype 1 Infection
Ledipasvir and Sofosbuvir for UntreatedHCV Genotype 1 Infection
RESPUESTA VIROLÓGICA SOSTENIDA(12 SEMANAS)
RESPUESTA VIROLÓGICA SOSTENIDA(12 SEMANAS)
LEDISPAVIR MAS SOFOSBUVIR 12 SEM. 99%
LEDISPAVIR MAS SOFOSBUVIR MAS RIBAVIRINA 12 SEM. 97%
LEDISPAVIR MAS SOFOSBUVIR 24 SEM. 98%
LEDISPAVIR MAS SOFOSBUVIR MAS RIBAVIRINA 24 SEM. 99%
LEDISPAVIR MAS SOFOSBUVIR 12 SEM. 99%
LEDISPAVIR MAS SOFOSBUVIR MAS RIBAVIRINA 12 SEM. 97%
LEDISPAVIR MAS SOFOSBUVIR 24 SEM. 98%
LEDISPAVIR MAS SOFOSBUVIR MAS RIBAVIRINA 24 SEM. 99%
Nezam Afdhal, et al N Engl J Med 2014Nezam Afdhal, et al N Engl J Med 2014
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
RESPUESTA VIROLÓGICA SOSTENIDA(12 SEMANAS)
RESPUESTA VIROLÓGICA SOSTENIDA(12 SEMANAS)
LEDISPAVIR MAS SOFOSBUVIR 12 SEM. 94%
LEDISPAVIR MAS SOFOSBUVIR MAS RIBAVIRINA 12 SEM. 96%
LEDISPAVIR MAS SOFOSBUVIR 24 SEM. 99%
LEDISPAVIR MAS SOFOSBUVIR MAS RIBAVIRINA 24 SEM. 99%
LEDISPAVIR MAS SOFOSBUVIR 12 SEM. 94%
LEDISPAVIR MAS SOFOSBUVIR MAS RIBAVIRINA 12 SEM. 96%
LEDISPAVIR MAS SOFOSBUVIR 24 SEM. 99%
LEDISPAVIR MAS SOFOSBUVIR MAS RIBAVIRINA 24 SEM. 99%
Nezam Afdhal, et al N Engl J Med 2014Nezam Afdhal, et al N Engl J Med 2014
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 12 SEM
LEDISPAVIR MAS SOFOSBUVIR 8 SEM
LEDISPAVIR MAS SOFOSBUVIR MAS RIBAVIRINA 8 SEM.
LEDISPAVIR MAS SOFOSBUVIR 12 SEM
94%94%
93% 93%
95% 95%
RESPUESTA VIROLÓGICA SOSTENIDA(12 SEMANAS)
RESPUESTA VIROLÓGICA SOSTENIDA(12 SEMANAS)
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
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.
Daclatasvir plus Sofosbuvir for PreviouslyTreated or Untreated Chronic HCV Infection
Daclatasvir plus Sofosbuvir for PreviouslyTreated or Untreated Chronic HCV Infection
RESPUESTA VIROLÓGICA SOSTENIDA(12 SEMANAS)
RESPUESTA VIROLÓGICA SOSTENIDA(12 SEMANAS)
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
Class III, Level AClass III, Level A
Telaprevir-, boceprevir-, or simeprevir-based regimensTelaprevir-, boceprevir-, or simeprevir-based regimens
Class III, Level AClass III, Level A
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.