TRATAMIENTO ANTIVIRAL DE LA CIRROSIS HEPÁTICA POR VIRUS DE LA HEPATITIS B Y C

TRATAMIENTO ANTIVIRAL DE LA CIRROSIS HEPÁTICA POR VIRUS DE LA HEPATITIS B Y C Dra. Ángeles Castro Servicio de Medicina Interna B Hospital Universitario de A Coruña Vigo, 15 de Enero de 2010

Progresión histológica 0 1 2 No Fibrosis Fibrosis Portal Septos periportales ó porto-portal 3 Numerosos septos Cirrosis 4

Cirrosis Hepática Compensada

Clasificación Child-Pugh: Puntos 1 2 3 Albúmina (g/dl) >3.5 3.0 a 3.5 <3.0 Bilirubina(mg/dL) <2 2.0 a 3.0 >3.0 INR <1.7 1.7 a 2.3 >2.3 Ascitis No Fácil control con diuréticos Mal control con diuréticos Encefalopatía No Grado 1-2 Grado 3-4 Ghany M, et al. In: Kasper DL, et al, eds. Harrison s Principles of Internal Medicine. 16 th Edition. McGraw-Hill; New York. 2005:1812-1813.

FACTORS ASSOCIATED WITH SURVIVAL AND FIRST HEPATIC DECOMPENSATION IN A LARGE PROSPECTIVE COHORT OF HIV CO-INFECTED PATIENTS WITH LIVER CIRRHOSIS. M López-Diéguez, JF Pascual, M Montes, C Quereda, MA Von Wichmann, J Berenguer, C Tural, JM Miró, F Pulido, E Ortega, A Arranz, J González-García, JR Arribas and the GESIDA 37/03-FIPSE 364665/03 Study Group. Poster Presentation at CROI2008 [1057]

SURVIVAL Compensated vs Decompensated Cumulative probability of survival p<0,0001 (log-rank) 0.92 0.53 Months Compensated 253 241 218 141 Decompensated 78 60 45 27

SURVIVAL ChildPughScore p<0,0001 (log-rank) Months C A B 0.96 Cumulative probability of survival

CHILD-PUGH SCORE A B C Mean (IC95%) 68 (65-70) 22 (18-26) 10 (6-13) Median (IC95%) NA 19 (13-25) 7 (5-9) 1 year probability 0.98 0.65 0.32 2 years probability 0.92 0.49 _ 3 years probability 0.92

Multivariate analysis: Hazard ratio of factors associated with decreased survival [HR, (CI), p]

PACIENTE CIRRÓTICO: CÓMO MANTENER EL EQUILIBRIO?

Manejo del paciente con cirrosis hepática VIH positivo 2.- Tratamientos específicos Valoración n de transplante hepático Si MELD > 15 ó Child-Pugh > 7 Terapia TARGA Terapia antiviral específica para el VHB ó VHC

Tratamiento antiviral del paciente con cirrosis hepática VIH-VHB VHB positivo Tratamiento con dos fármacos f rmacos activos frente al VHB. TTENOFOVIR + FTC ó LAMIVUDINA -TENOFOVIR + TELBIVUDINA ADEFOVIR + TELBIVUDINA ADEFOVIR + LAMIVUDINA ADEFOVIR + ENTECAVIR Datos de seguridad y eficacia a mediolargo plazo?

Tratamiento antiviral del paciente con cirrosis hepática VIH-VHB VHB positivo EXCEPCIONALMENTE, si utilizamos solo terapia para el VHB: ADEFOVIR ó Telbivudina(?) Si iniciamos monoterapia,, se recomienda añadir adir un 2º 2 fármaco si ADN-VHB es + a las 24 semanas: ADEFOVIR + Telbivudina ( datos de seguridad?) INICIAR TARGA, asociando Tenofovir/FTC

Tratamiento antiviral del paciente con cirrosis hepática VIH-VHC VHC positivo

APRICOT: Factores de riesgo asociados con la descompensación hepática en pacientes VIH/VHC Factores de riesgo de descompensación hepática tica* Aumento de: Bilirrubina total Fosfatasa alcalina Descenso de: Albúmina Plaquetas Hemoglobina Odds Ratio 1,12 1,02 0,83 0,96 0,53 Valor P <0,001 <0,001 <0,002 <0,001 <0,001 Tratamiento con ddi 4,06 <0,03 * Análisis Univariado. Mauss S et al. AIDS 2004; 18: F21-F25

AASLD Practice Guidelines: An Update clinicaloptions.com/hepatitis Posttreatment Outcomes in Patients With Advanced Fibrosis With/Without SVR Liver-Related Death (%) 50 5-yr occurrence Liver-Related Death SVR: 4.4% (CI: 0% to 12.9%) No SVR: 12.9% (CI: 7.7% to 18.0%) P =.024 (log likelihood) 5-yr occurrence Liver Failure SVR: 0% No SVR: 13.3% (CI: 8.4% to 18.2%) P =.001 (log likelihood) Year At risk 337 261 192 160 124 95 79 49 31 Events 0 5 11 16 20 24 25 28 30 At risk 142 76 48 35 25 14 8 6 5 Events 0 0 0 0 0 1 1 1 1 Year At risk 337 256 183 155 121 92 74 44 27 Events 0 8 21 24 27 29 31 35 35 At risk 142 76 48 35 25 14 8 6 5 Events 0 0 0 0 0 1 1 1 1

AASLD Practice Guidelines: An Update clinicaloptions.com/hepatitis Incidence of HCC in Patients With Advanced Fibrosis With/Without SVR HCC (%) 100 80 60 40 20 0 5-yr occurrence SVR: 9.2% (95% CI: 0.0% to 19.6%) No SVR: 13.1% (95% CI: 7.6% to 18.6%) P =.192 (log likelihood) 0 1 2 3 4 5 6 7 Years No SVR SVR At risk 337 259 188 153 117 90 71 43 30 Events 0 5 8 13 18 22 27 29 30 8 No SVR SVR SVR At risk 142 76 48 35 24 14 8 6 5 Events 0 0 1 1 3 3 3 3 3 Veldt BJ, et al. Ann Intern Med. 2007;147:677-684. Reproduced with permission.

AASLD Practice Guidelines: An Update clinicaloptions.com/hepatitis

AASLD Practice Guidelines: An Update clinicaloptions.com/hepatitis

AASLD Practice Guidelines: An Update clinicaloptions.com/hepatitis

AASLD Practice Guidelines: An Update clinicaloptions.com/hepatitis

AASLD Practice Guidelines: An Update clinicaloptions.com/hepatitis

AASLD Practice Guidelines: An Update clinicaloptions.com/hepatitis HALT-C: Final Results of Maintenance PegIFN alfa-2a in Nonresponders No significant difference between arms in any primary outcome 34.1% vs 33.8%; HR: 1.01 (95% CI: 0.81-1.26) Study Arm Baseline Fibrosis Any Primary Outcome, % Low-dose pegifn alfa-2a 90 µg/wk vs control group had Greater reductions in HCV RNA and ALT (P <.0001) Greater reductions in necroinflammation (P <.001) No reduction or difference in fibrosis in either arm Di Bisceglie AM, et al. N Engl J Med. 2008;359:2429-2441. Death, % HCC, % CTP Score 7, % PegIFN alfa-2a 3/4 36.7 2.6 2.6 3.2 90 µg/wk (n = 517) 5/6 30.2 2.4 1.9 17.8 Control (n = 533) 3/4 35.5 0.6 1.6 3.2 5/6 31.2 2.7 4.6 14.6

AASLD Practice Guidelines: An Update clinicaloptions.com/hepatitis EPIC3: Clinical Events Reduced in Subset of Patients on Maintenance Peginterferon Clinical events not significantly reduced in patients receiving peginterferon alfa-2b maintenance therapy vs observation overall (P =.144), but significant benefit observed in subset of patients with portal hypertension at baseline (P =.007) Patients With Portal Hypertension at Baseline (%) 100 80 60 40 20 0 32.6 10.3 16.3 2.6 2.3 2.6 Any Clinical Event Ascites Observed control (n = 43) 14.0 Childs-Pugh Class C Variceal Bleeding Bruix J, et al. EASL 2009. Abstract 49. Reproduced with permission. Peginterferon alfa-2b 0.5 µg/kg/wk (n = 39) 4.7 7.7 4.7 0 2.6 2.3 0 2.3 0 HCC Hepatic Encephalopathy Liver Transplant Death

AASLD Practice Guidelines: An Update clinicaloptions.com/hepatitis HCV Therapy in Decompensated Cirrhotics Awaiting Liver Transplantation Patients (%) 100 80 60 40 Everson [1] Forns [2] Thomas [3] Crippin [4] 20 0 EVR *Regardless of achieving SVR pretransplantation. SVR Patients Receiving Transplant HCV Free Posttransplant* 1. Everson GT, et al. Hepatology. 2005;42:255-262. 2. Forns X, et al. J Hepatol. 2003;39:389-396. 3. Thomas RM, et al. Liver Transpl. 2003;9:905-915. 4. Crippin JS, et al. Liver Transpl. 2002;8:350-355.

Trata86 649.98 rew*1to antiviral del pacw*1t

Tratamiento antiviral del paciente con cirrosis hepática VIH-VHC VHC positivo *Los pacientes con cirrosis hepática VHC+ compensada, Child A, pueden ser tratados con peginterferon + ribavirina, requiriendo monitorización estrecha de los efectos adversos (Nivel A, clase I) *La cirrosis hepática VHC + descompensada, debe ser valorada para transplante hepático (Nivel B, clase I) *La terapia con interferon a dosis baja puede ser utilizado en cirrosis hepática descompensada (Child B ó C), durante tiempo prolongado, preferentemente en pacientes que hayan sido aceptados como candidatos a transplante (Nivel B, clase IIB).

CIRROSIS EN EL PACIENTE VIH +: MANTENDREMOS EL EQUILIBRIO? FELIZ AÑO 2010! y gracias por vuestra atención