Article information
Actualmente se estima que en España hay entre 60.000 y 80.000 personas coinfectadas por el virus de la inmunodeficiencia humana (VIH) y el virus de la hepatitis C (VHC) y de 5.000 a 10.000 personas infectadas por VIH y virus de la hepatitis B (VHB), de los cuales el 10-15% está afectado de una cirrosis hepática. Por ello la enfermedad hepática terminal es una de las primeras causas de muerte en nuestro país. El trasplante hepático es la única alternativa terapéutica en estos casos. La experiencia acumulada en América del Norte y Europa en los últimos 5 años indica que la supervivencia a los 3 años del trasplante hepático es similar a la de los pacientes VIH negativos. Los criterios utilizados para seleccionar a los pacientes VIH han sido: no haber tenido infecciones oportunistas, tener una cifra de linfocitos CD4 > 100 cél./mm3 y una carga viral del VIH suprimible con tratamiento antirretroviral. En España, donde la mayoría de pacientes eran antiguos drogadictos, se exigía además una abstinencia a la heroína y cocaína de 2 años de duración, y el paciente podía estar en el programa de metadona. En España se han realizado 26 trasplantes hepáticos en otros tantos pacientes, de los cuales sólo dos han fallecido (7%) tras una mediana de seguimiento de 8 meses (límites, 1-28). Los principales problemas en el período postrasplante en todas las series han sido la recidiva de la infección por el VHC, que es la principal causa de mortalidad postrasplante, y las interacciones farmacocinéticas y farmacodinámicas entre los antirretrovirales y los inmunosupresores. La experiencia del tratamiento con interferón pegilado y ribavirina es escasa en esta población.
Palabras clave:
Trasplante hepático
VHC
VHB
VIH
España
According to current estimates, there are 60,000 to 80,000 HIV and HCV coinfected individuals in Spain, and 5,000 to 10,000 HIV and HBV coinfected individuals. Among these patients, 10% to 15% have liver cirrhosis. Thus, end-stage liver disease is one of the major causes of death in our country. Liver transplantation is the only therapeutic option for these patients. Accumulated experience in North America and Europe in the last five years indicates that three-year survival in HIV-positive liver transplant recipients is similar to that of HIV-negative recipients. The selection criteria for HIV transplant candidates includes the following: no history of opportunistic infections, CD4 lymphocyte count higher than 100 cells/mm3, and HIV viral load suppressible with antiretroviral treatment. In Spain, where the majority of patients are former drug abusers, complete abstinence from heroin or cocaine use during two years is also required, with the possibility of the patient being in a methadone program. To date 26 hepatic transplants have been performed in the same number of patients, with only two deaths (7%) after a median follow-up of eight months (1-28). The main problems in the post-transplantation period in all the series has been recurrent HCV infection, which is the principle cause of post-transplantation mortality, and pharmacokinetic and pharmacodynamic interactions between the antiretroviral and immunosuppressive agents. There is little experience with pegylated interferon and ribavirin treatment in this population.
Key words:
Hepatic transplant
HCV
HBV
HIV
Spain
Full text is only aviable in PDF
Bibliografía
[1.]
R.H. Rubin.
Transplant Int, 1 (1988), pp. 36-42
[2.]
F.J. Palella, K.M. Delaney, A.C. Moorman, M.O. Loveless, J. Fuhrer, G.A. Satten, et al.
Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatients Study Investigators.
N Engl J Med, 338 (1998), pp. 853-860
[3.]
R. Detels, P. Tarwater, J.P. Phair, J. Margolicck, S.A. Riddler, A. Muñoz.
Effectiveness of potent antiretroviral therapies on the incidence of opportunistic infections before and after AIDS diagnosis.
AIDS, 15 (2001), pp. 347-355
[4.]
V. Soriano, J.M. Miró, J. García-Samaniego, J. Torre-Cisneros, M. Núñez, J. Del Romero, et al.
Consensus conference on chronic viral hepatitis and HIV infection: updated Spanish recommendations.
J Viral Hepat, 11 (2004), pp. 2-17
[5.]
J. González, L. Guerra.
Grupo de trabajo para la elaboración de recomendaciones sobre las hepatitis virales en pacientes infectados por el VIH. Coinfección por el VIH y virus de las hepatitis A, B y C en pacientes adultos. Revisión y recomendaciones de GESIDA/PNS..
Enfermedades Asociadas al VIH (2000-2002). Documentos de Consenso de GESIDA, pp. 173-225
[6.]
M. Pouplana.
Morbilidad y mortalidad asociadas a hepatopatía crónica viral en pacientes infectados por el virus de la inmunodeficiencia humana.
Med Clin (Bar, 104 (1995), pp. 641-644
[7.]
C.T. Staples, D. Rimland, D. Dudas.
Hepatitis C in the HIV (human immunodeficiency virus) Atlanta V.A. (Veterans Affairs Medical Center) Cohort Study (HAVACS): the effect of coinfection on survival.
Clin Infect Dis, 29 (1999), pp. 150-154
[8.]
R. Romero, M.G. Rumi, M.F. Donato, M.A. Cargnel, P. Vigano, M. Mondelli, et al.
Hepatitis C is more severe in drug users with human immunodeficiency virus infection.
J Viral Hepat, 7 (2000), pp. 297-301
[9.]
V. Soriano, M. Sulkowski, C. Bergin, A. Hatzakis, P. Cacoub, C. Katlama, et al.
Care of patients with chronic hepatitis C and HIV co-infection: recommendations from the HIV-HCV International Panel.
AIDS, 16 (2002), pp. 813-828
[10.]
I. Bica, B. McGovern, R. Dhar, D. Stone, K. McGowan, R. Scheib, et al.
Increasing mortality due to end-stage liver disease in patients with human immunodeficiency virus infection.
Clin Infect Dis, 32 (2001), pp. 492-497
[11.]
X. Camino, J.A. Iribarren, J. Arrizabalaga, F. Rodríguez, A.M. Von Wichmann.
Causes of mortality among patients infected with the human immunodeficiency virus in the era of high active antiretroviral therapy.
Enferm Infecc Microbiol Clin, 19 (2001), pp. 85-86
[12.]
B. Soto, A. Sánchez-Quijano, L. Rodrigo, J.A. Del Olmo, M. García-Bengoechea, J. Hernández-Quero, et al.
Human immunodeficiency virus infection modifies the natural history of chronic parenterally-adquired hepatitis C with an unusually rapid progression to cirrhosis.
J Hepatol, 26 (1997), pp. 1-5
[13.]
M. Pérez-Olmeda, M. Núñez, M. Romero, J. González, A. Castro, J.R. Arribas, et al.
Pegylated IFN-a2b plus ribavirin as therapy for chronic hepatitis C in HIV-infected patients.
AIDS, 17 (2003), pp. 1023-1028
[14.]
L. Moreno, C. Quereda, A. Moreno, M.J. Pérez-Elías, A. Antela, J.L. Casado, et al.
Pegylated interferon-α2b plus ribavirin for the treatment of chronic hepatitis C in HIV-infected patients.
AIDS, 18 (2004), pp. 1-7
[15.]
Perronne C, Carrat F, Bani-Sadr F, Pol S, Rosenthal E, Lunel F, et al. Final results of ANRS HC02-RIBAVIC: A randomized controlled trial of pegylated-interferon-alfa-2b plus ribavirin vs interferon-alfa-2b plus ribavirin for the initial treatment of chronic hepatitis C in HIV co-infected patients. En: 11th Conference on Retroviruses and Opportunistic Infections [Abstract 117LB]. San Francisco, February 8-11, 2004.
[16.]
R. Chung, J. Andersen, P. Volberding, G.K. Robbins, T. Liu, K.E. Sherman, et al.
Peginterferon Alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons.
N Engl J Med, 351 (2004), pp. 451-459
[17.]
F.J. Torriani, M. Rodríguez-Torres, J.K. Rockstroh, E. Lissen, J. González-García, A. Lazzarin, et al.
Peginterferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients.
N Engl J Med, 351 (2004), pp. 438-450
[18.]
Policies & Bylaws. Alexandria, Va.: United Network for Organ Sharing, 2001. Disponible en; (http://www.unos.org/frame_Default.asp?Category = aboutpolicies
[20.]
S.D. Halpern, P.A. Ubel, A.L. Caplan.
Solid-Organ Transplantation in HIV-Infected patients.
N Engl J Med, 347 (2002), pp. 284-287
[21.]
A.A. Prachalias, A. Pozniak, C. Taylor, P. Srinivasan, P. Muiesan, J. Wendom, et al.
Liver transplantation in adults coinfected with HIV.
Transplantation, 72 (2001), pp. 1684-1688
[22.]
P.C. Kuo, P.G. Stock.
Transplantation in the HIV + patient.
Am J Transplant, 1 (2001), pp. 13-17
[23.]
T. Steinman, B.N. Becker, A.E. Frost, K.M. Olthoff, F.W. Smart, W.N. Suki, et al.
Guidelines for the referral and management of patients eligible for solid organ transplantation.
Transplantation, 71 (2001), pp. 1189-1204
[24.]
P. Costigliola, F. Tumietto, A. Zagnoli, F. Chiodo.
for Project HOST. Need for liver transplant in HIV-positive patients: first results of a specific survey in Italy, Project HOST.
AIDS, 17 (2003), pp. 2119-2121
[25.]
M.E. Roland, P.G. Stock.
Review of solid-organ transplantation in HIV-infected patients.
Transplantation, 75 (2003), pp. 425-429
[26.]
J.S. Dummer, E. Siegfried, M.K. Breinig, M. Ho, C.R. Rinaldo, P. Gupta, et al.
Infection with human immunodeficiency virus in the Pittsburgh transplant population.
Transplantation, 47 (1989), pp. 134-140
[27.]
A.G. Tzakis, M.H. Cooper, J.S. Dummer, M. Ragni, J.W. Ward, T.E. Starzl.
Transplantation in HIV + patients.
Transplantation, 49 (1990), pp. 354-358
[28.]
A. Erice, F.S. Rhame, R.C. Heussner, D.L. Dunn, H.H. Balfour.
Human immunodeficiency virus infection in patients with solid-organ transplants: report of five cases and review.
Rev Infect Dis, 13 (1991), pp. 537-547
[29.]
A. Schwarz, G. Offermann, F. Keller, I. Bennhold, J. L’Age-Stehr, P.H. Krause, et al.
The effect of cyclosporine on the progression of human immunodeficiency virus type 1 infection transmitted by transplantation-data of four cases and review of the literature.
Transplantation, 55 (1993), pp. 95-103
[30.]
F. Bouscarat, D. Samuel, F. Simon, P. Debat, H. Bismuth, A.G. Saimot.
An observational study of 11 French liver transplant recipients infected with human immunodeficiency virus type 1.
Clin Infect Dis, 19 (1994), pp. 854-859
[31.]
F.H. Gordon, P.K. Mistry, C.A. Sabin, C.A. Lee.
Outcome of orthotropic liver transplantation in patients with haemophilia.
Gut, 42 (1998), pp. 744-749
[32.]
M.V. Ragni, S.F. Dodson, S.C. Hunt, F.A. Bontempo, J.J. Fung.
Liver transplantation in haemophilia patients with acquired immunodeficiency syndrome.
Blood, 93 (1999), pp. 1113-1114
[33.]
P.J. Gow, D. Mutimer.
Liver transplantation for an HIV-positive patient in the era of high active antiretroviral therapy.
AIDS, 15 (2001), pp. 291-292
[34.]
K. Schliefer, W. Paar, G. Aydermir, M. Wolff, J.K. Rockstroh, U. Spengler, et al.
Orthotopic liver transplantation in a 33-years-old patient with fulminate hepatitis B and HIV infection.
Dtsch Med Wochenschr, 125 (2000), pp. 523-526
[35.]
D. Samuel, D. Vittecoq, J.C. Duclos-Vallee, C. Feray, E. Teicher, D. Azoulay, et al.
Liver transplantation for HCV cirrhosis in HIV-HCV coinfected patients, evaluation of antiretroviral toxicity and f HCV recurrence.
Hepatology, 36 (2002), pp. 231A
[36.]
K. Radecke, M. Miller, B. Ross, U. Treichel, G. Gerken.
Short term outcome in five HIV infected patients with terminal liver disease after orthotopic liver transplantation.
Hepatology, 36 (2002), pp. 190A
[37.]
P.G. Stock, M.E. Roland, L. Carlson, C.E. Freise, J.P. Roberts, R. Hirose, et al.
Kidney and liver transplantation in human immunodeficiency virus-infected patients: a pilot safety and efficacy study.
Transplantation, 76 (2003), pp. 370-375
[38.]
A. Bonham, G.W. Neff, A.G. Tzakis, M. Ragni, D. Jayaweera, E.R. Schiff, et al.
Orthotopic liver transplantation in patients with human immunodeficiency virus and end-stage liver disease.
Liver Transpl, 9 (2003), pp. 239-247
[39.]
M.V. Ragni, S.H. Belle, K. Im, G. Neff, M. Roland, P. Stock, et al.
Survival of human immunodeficiency virus-infected liver transplant recipients.
J Infect Dis, 188 (2003), pp. 1412-1420
[40.]
Roland ME, Carlson L, Ragni M, Rohal S, Keller M, Murphy B, et al. Solid organ transplantation in HIV-infected recipients: 47 cases in the HAART era (Abstract MoOrB1060). En: XIV International AIDS Conference. Barcelona, Spain, 2002.
[41.]
M.E. Roland, D.V. Havlir.
Responding to organ failure in HIV-infected patients.
N Engl J Med, 348 (2003), pp. 2279-2281
[42.]
A. Rafecas, G. Rufi, J. Fabregat, X. Xiol.
Liver transplantation in a patient infected with HIV.
Med Clin (Barc, 119 (2002), pp. 596
[43.]
R. González Alonso, R. Bárcena, C. Blesa, M. García, A. Moreno, J. Fortún, et al.
Liver transplantation in a patient coinfected with human immunodeficiency virus and hepatitis C.
Transplant Proc, 35 (2003), pp. 1846-1847
[44.]
Miró JM, Rufí G, Bárcena R, Vargas V, Valdivieso A, Rimola A, et al. Trasplante hepático (TH) en pacientes infectados por el VIH: análisis de 21 casos trasplantados en España en la era del tratamiento antirretroviral de gran actividad (TARGA) (2002-2004). XI Congreso Nacional de Enfermedades Infecciosas y Microbiología Clínica (SEIMC) [abstract 509]. Bilbao, 16-19 mayo 2004.
[45.]
J.M. Miró, E. Buira, J. Mallolas, T. Gallart, A. Moreno, L. Zamora, et al.
Linfocitos CD4+ e infecciones oportunistas y neoplasias en pacientes con infección por el VIH.
Med Clin (Barc, 102 (1994), pp. 566-570
[46.]
G.W. Neff, D. Jayaweera, A. Tzakis.
Liver transplantation for HIV-infected patients with end-stage liver disease.
Curr Opin Organ Transplantation, 7 (2002), pp. 114-123
[47.]
M. Rayes, W. Bechstein, H. Volk, S.G. Tullius, S.G. Nussler, U. Nauman, et al.
Distribution of lymphocyte subtypes in liver transplant recipients.
Transplant Proc, 29 (1997), pp. 501-502
[48.]
A. Rimola, V. Cuervas-Mons, G. Clemente, J. Quiroga, H. Andreu, J. Martorell, et al.
Prospective, multicenter study comparing two immunosuppressive regimes in liver transplantation: an anti-interleukin-2 receptor monoclonal antibody-based regimen versus a cyclosporine-based regimen. Joint Congress on Liver Transplantation. London, 1995.
Liver Transpl Sur, 1 (1995), pp. 433
[49.]
W. Yates, M. Martin, D. LaBrecque, D. Hillebrand, M. Voigt, D. Pfab.
A model to examine the validity of the 6-month abstinence criterion for liver transplantation.
Alcohol Clin Exp Res, 22 (1998), pp. 513-517
[50.]
J. Neuberger.
Transplantation for alcoholic liver disease.
J Hepatol, 36 (2002), pp. 130-137
[51.]
L.U. Liu, T.D. Schiano, N. Lau, M. O’Rourke, A.D. Min, S.H. Sigal, et al.
Survival and risk of recidivism in methadone-dependent patients undergoing liver transplantation.
Am J Transplant, 3 (2003), pp. 1273-1277
[52.]
Miró JM, Blanco JL, Rimola A, Grande L, Moreno A, Mestre G
[53.]
C. Quereda, L. Moreno, M.E. Moreno, M. Rivero, S. Diz, M.E. Bermúdez.
Impact o highly active antirretroviral therapy (HART) in the natural history of decompensated liver cirrhosis in HIV-infected patients [Abstract I-204].
En: 41st Interscience Conference on Antimicrobial Agents and Chemotherapy, pp. 311
[54.]
Santín M, Shaw E, Euba G, Gudiol C, López C, Xiol X, et al. Clinical characteristics and outcome of spontaneous bacterial peritonitis (SBP) in cirrhotic patients with HIV infection [Abstract H-1921]. En: 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, 2003; p. 329.
[55.]
Von Wichmann MA, Arévalo S, Zapata E, Rodríguez Arrondo F, Arrizabalaga J, Iribarren JA, et al. Survival in HIV+ patients with viral hepatitis after ascites has developed [Abstract V-782]. En: 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology Chicago, 2003; p. 496.
[56.]
M.E. Roland, L. Bernard, J. Braff, P.G. Stock.
Key clinical, ethical, and policy issues in the evaluation of the safety and effectiveness of solid organ transplantation in HIV-infected patients.
Arch Intern Med, 163 (2003), pp. 1773-1778
[57.]
Iribarren JA, Labarga P, Rubio R, Berenguer J, Miró JM, Antela A, et al. Recomendaciones de GESIDA/PNS respecto al tratamiento antirretroviral en pacientes adultos infectados por el virus de la inmunodeficiencia humana (octubre 2004). Enferm Infecc Microbiol Clin 2004. En prensa.
[58.]
A.K. Jain, R. Venkataramanan, R. Shapiro, V.P. Scantlebury, S. Potdar, C.A. Bonham, et al.
The interaction between antiretroviral agents and tacrolimus in liver and kidney transplant patients.
Liver Transpl, 8 (2002), pp. 841-845
[59.]
K. Brinkman, F. Huysmans, D.M. Burger.
Pharmacokinetic interaction between saquinavir and cyclosporine.
Ann Intern Med, 129 (1998), pp. 914-915
[60.]
D.L. Paterson, N. Singh.
Interactions between tacrolimus and antimicrobial agents.
Clin Infect Dis, 25 (1997), pp. 1430-1440
[61.]
A.K. Jain, R. Venkataramanan, J.A. Fridell, M. Gadomski, L.M. Shaw, M. Ragni, et al.
Nelfinavir, a proteasa inhibitor, increases sirolimus levels in liver transplantation patient: a case report.
Liver Transpl, 8 (2002), pp. 838-840
[62.]
A. Tseng, M.E. Nguyen, C. Cardella, A. Humar, J. Conly.
Probable interaction between efavirenz and cyclosporine.
AIDS, 16 (2002), pp. 505-506
[63.]
Tuset M, Miró JM, Codina C, Ribas J. Interacciones en VIH [consulta: 15 de junio de 2004]. Disponible en; http://www.interaccioneshiv.com/
[64.]
D. Margolis, S. Kewn, J.J. Coull, L. Ylisastigui, D. Turner, H. Wise, et al.
The addition of mycophenolate mofetil to antiretroviral therapy including abacavir is associated with depletion of intracellular deoxyguanosine triphosphate and a decrease in plasma HIV-1 RNA.
J Acquir Immune Defic Syndr, 31 (2002), pp. 45-49
[65.]
G. Vennarecci, G.M. Ettorre, M. Antonini, M. Maritti, P. Moricca, G. D’Ó, et al.
Acute liver toxicity of antiretroviral therapy (HAART) after liver transplantation in a patient with HIV-HCV coinfection associated hepatocarcinoma (HCC.
Tumori, 89 (2003), pp. 159-161
[66.]
M.S. Sulkowski, D.L. Thomas, R.E. Chaisson, et al.
Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection.
JAMA, 283 (2000), pp. 74-80
[67.]
H. Groux, G. Torpier, D. Monte, Y. Mouton, A. Capron, J.C. Ameisen.
Activation- induced death by apoptosis in CD4+ T cells from human immunodeficiency virus-infected asymptomatic individuals.
J Exp Med, 175 (1992), pp. 331-340
[68.]
J.J. Coull, D. Turner, T. Melby, M.R. Betts, R. Lainer, D.M. Margolis.
A pilot study of the use of mycophenolate mofetil as a component of therapy for multidrug-resistant HIV-1 infection.
J Acquir Immune Defic Syndr, 26 (2001), pp. 423-434
[69.]
A. Chapuis, P. Rizzardi, C. D’Agostini, A. Attinger, C. Knabenhans, S. Fleury, et al.
Effects of mycophenolic acid on human immunodeficiency virus infection in vitro and in vivo.
Nat Med, 6 (2000), pp. 762-768
[70.]
J. Ayats-Ardite, J.M. Cisneros-Herreros, J.L. Pérez-Sáenz, J. Torre-Cisneros.
Grupo de Estudio de Infecciones en Trasplantados (GESITRA). Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC). Evaluación de las enfermedades infecciosas en el candidato a un trasplante de órgano sólido.
Enferm Infecc Microbiol Clin, 20 (2002), pp. 448-461
[71.]
T. Bizollon, C. Ducerf, C. Trepo, D. Multimer.
Hepatitis C virus recurrence after liver transplantation.
Gut, 44 (1999), pp. 575-578
[72.]
D. Samuel, C. Feray.
Recurrent hepatitis C after liver transplantation: clinical and therapeutic issues.
J Viral Hepat, 7 (2000), pp. 87-92
[73.]
D. Tolan, M.H. Davies, C.E. Millson.
Fibrosing cholestatic hepatitis after liver transplantation in a patient with hepatitis C and HIV infection.
N Engl J Med, 345 (2001), pp. 1781
[74.]
M.W. Vogt, K.L. Hartsshorn, P.A. Furman, T.C. Chou, J.A. Fyfe, L.A. Coleman, et al.
Ribavirin antagonizes the effect of azidothymidine on HIV replication.
Science, 235 (1987), pp. 1376-1379
[75.]
J. Balzarini, C.K. Lee, P. Herdewijn, E. De Clercq.
Mechanism of the potentiating effect of ribavirin on the activity of 2’,3’-dideoxynosine against human immunodeficiency virus.
J Biol Chem, 266 (1991), pp. 21509-21514
[76.]
A. Lafeuillade, G. Hittinger, S. Chadapaud.
Increased mitochondrial toxicity with ribavirin in HIV/HCV coinfection.
Lancet, 357 (2001), pp. 280-281
[77.]
D. Salmon-Ceron, L. Chauvelot-Moachon, S. Abad, B. Silbermann, P. Sogni.
Mitochondrial toxicity effects and ribavirin.
Lancet, 357 (2001), pp. 1803-1804
[78.]
García-Benayas T, Blanco F, Soriano V., Weight loss in HIV-infected patients receiving interferon plus ribavirin for chronic hepatitis C. N Engl J Med 2002
[79.]
D. Samuel, R. Muller, G. Alexander, et al.
Liver transplantation in European patients with the hepatitis B surface antigen.
N Engl J Med, 329 (1993), pp. 1842-1847
