Management of end stage liver disease (ESLD): What is the current role of orthotopic liver transplantation (OLT)?

Liver disease due to chronic hepatitis B and C is now a leading cause of morbidity and mortality among HIV-infected patients in the developed world, where classical opportunistic complications of severe immunodeficiency have declined dramatically. Orthotopic liver transplantation (OLT) is the only therapeutic option for patients with end-stage liver disease (ESLD). Accumulated experience in North America and Europe in the last 5 years indicates that 3-year survival in selected HIV-infected recipients of liver transplants was similar to that of HIV-negative recipients. So, HIV infection by itself is not therefore a contraindication for liver transplantation. As survival of HIV-infected patients with ESLD is shorter than non-HIV-infected population, the evaluation for OLT should be made after the first liver decompensation. The current selection criteria for HIV-positive transplant candidates include: no history of opportunistic infections or HIV-related neoplasms, CD4 cell count >100 cells/mm3, and plasma HIV viral load suppressible with antiretroviral treatment. For drug abusers, a 2-year abstinence from heroin and cocaine is required, although patients can be in a methadone programme. The main problems in the post-transplant period are pharmacokinetic and pharmacodynamic interactions between antiretrovirals and immunosuppressive drugs, and the management of relapse of HCV infection. Up to now, experience with pegylated interferon and ribavirin is scarce in this population. Currently, HCV re-infection is the main cause for concern. Liver disease due to chronic hepatitis B and C is now a leading cause of morbidity and mortality among HIV-infected patients in the developed world, where classical opportunistic complications of severe immunodeficiency have declined dramatically. Orthotopic liver transplantation (OLT) is the only therapeutic option for patients with end-stage liver disease (ESLD). Accumulated experience in North America and Europe in the last 5 years indicates that 3-year survival in selected HIV-infected recipients of liver transplants was similar to that of HIV-negative recipients. So, HIV infection by itself is not therefore a contraindication for liver transplantation. As survival of HIV-infected patients with ESLD is shorter than non-HIV-infected population, the evaluation for OLT should be made after the first liver decompensation. The current selection criteria for HIV-positive transplant candidates include: no history of opportunistic infections or HIV-related neoplasms, CD4 cell count >100 cells/mm3, and plasma HIV viral load suppressible with antiretroviral treatment. For drug abusers, a 2-year abstinence from heroin and cocaine is required, although patients can be in a methadone programme. The main problems in the post-transplant period are pharmacokinetic and pharmacodynamic interactions between antiretrovirals and immunosuppressive drugs, and the management of relapse of HCV infection. Up to now, experience with pegylated interferon and ribavirin is scarce in this population. Currently, HCV re-infection is the main cause for concern. 1. IntroductionEnd-stage liver disease (ESLD), mainly caused by hepatitis C virus (HCV), is becoming an important cause of death among human immunodeficiency virus-1 (HIV-1) infected patients in the highly active antiretroviral therapy (HAART) era [[1]Bica I. McGovern B. Dhar R. Stone D. McGowan K. Scheib R. et al.Increasing mortality due to end-stage liver disease in patients with human immunodeficiency virus infection.Clin Infect Dis. 2001; 32: 492-497Crossref PubMed Scopus (894) Google Scholar]. Orthotopic liver transplantation (OLT) is the only therapeutic option for patients with ESLD. Until a few years ago, infection by HIV was an absolute contraindication to any type of transplant [[2]Rubin R.H. Tolkoff-Rubin N.E. The problem of human immunodeficiency virus (HIV) infection and transplantation.Transpl Int. 1988; 1: 36-42Crossref PubMed Google Scholar]. However, the spectacular improvement in prognosis observed in HIV-infected patients after the introduction of HAART in 1996 has meant that HIV infection by itself is not a contraindication for liver transplantation. This paper does not aim to provide an exhaustive review of the matter at hand, which has already been amply studied in other recent reviews [3Samuel D. Duclos Vallee J.C. Teicher E. Vittecoq D. Liver transplantation in patients with HIV infection.J Hepatol. 2003; 39: 3-6Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar, 4Roland M.E. Stock P.G. Review of solid-organ transplantation in HIV-infected patients.Transplantation. 2003; 75: 425-429Crossref PubMed Scopus (123) Google Scholar, 5Fung J. Eghtesad B. Patel-Tom K. DeVera M. Chapman H. Ragni M. Liver transplantation in patients with HIV infection.Liver Transpl. 2004; 10: S39-S53Crossref PubMed Google Scholar, 6Neff G.W. Sherman K.E. Eghtesad B. Fung J. Review article: current status of liver transplantation in HIV-infected patients.Aliment Pharmacol Ther. 2004; 20: 993-1000Crossref PubMed Scopus (15) Google Scholar, 7Miró J.M. Montejo M. Rufi G. Barcena R. Vargas V. Rimola A. et al.Liver transplantation in patients with HIV infection: a reality in 2004.Enferm Infecc Microbiol Clin. 2004; 22: 529-538PubMed Google Scholar]. Our objective is to define the criteria to select HIV-infected patients for OLT, taking into account that this field is evolving continuously and the indications for OLT or management of these patients may change as more evidence becomes available.2. Experience of OLT in HIV infected patients in the HAART period (1996–2005)Initial attempts at OLT in HIV infected patients before the introduction of HAART regimens (before 1996) provided very poor results. Putting together the most important case series published [8Tzakis A.G. Cooper M.H. Dummer J.S. Ragni M. Ward J.W. Starzl T.E. Transplantation in HIV+ patients.Transplantation. 1990; 49: 354-358Crossref PubMed Scopus (164) Google Scholar, 9Erice A. Rhame F.S. Heussner R.C. Dunn D.L. Balfour H.H. Human immunodeficiency virus infection in patients with solid-organ transplants: report of five cases and review.Rev Infect Dis. 1991; 13: 537-547Crossref PubMed Scopus (129) Google Scholar, 10Bouscarat F. Samuel D. Simon F. Debat P. Bismuth H. Saimot A.G. An observational study of 11 French liver transplant recipients infected with human immunodeficiency virus type 1.Clin Infect Dis. 1994; 19: 854-859Crossref PubMed Scopus (75) Google Scholar, 11Gordon F.H. Mistry P.K. Sabin C.A. Lee C.A. Outcome of orthotropic liver transplantation in patients with haemophilia.Gut. 1998; 42: 744-749Crossref PubMed Scopus (135) Google Scholar], 3-year survival was only 44% (Table 1). Most patients died because of HIV-disease progression, being graft function normal in many cases. However, since the introduction of HAART in 1996, HIV infected recipients of liver transplantation have improved their short- and mid-term survival. Accumulated experience in North America and Europe in the last 7–8 years, has shown that in more than 50 OLT cases [5Fung J. Eghtesad B. Patel-Tom K. DeVera M. Chapman H. Ragni M. Liver transplantation in patients with HIV infection.Liver Transpl. 2004; 10: S39-S53Crossref PubMed Google Scholar, 6Neff G.W. Sherman K.E. Eghtesad B. Fung J. Review article: current status of liver transplantation in HIV-infected patients.Aliment Pharmacol Ther. 2004; 20: 993-1000Crossref PubMed Scopus (15) Google Scholar], 80% of patients survived with different periods of follow-up. In two-thirds of cases, the primary indication of OLT was HCV co-infection [5Fung J. Eghtesad B. Patel-Tom K. DeVera M. Chapman H. Ragni M. Liver transplantation in patients with HIV infection.Liver Transpl. 2004; 10: S39-S53Crossref PubMed Google Scholar, 6Neff G.W. Sherman K.E. Eghtesad B. Fung J. Review article: current status of liver transplantation in HIV-infected patients.Aliment Pharmacol Ther. 2004; 20: 993-1000Crossref PubMed Scopus (15) Google Scholar]. In a multicentre and multinational retrospective study performed by Ragni et al. [[12]Ragni M.V. Belle S.H. Im K. Neff G. Roland M. Stock P. et al.Survival of human immunodeficiency virus-infected liver transplant recipients.J Infect Dis. 2003; 188: 1412-1420Crossref PubMed Scopus (198) Google Scholar], including 23 HIV-infected patients who underwent OLT, survival at 3 years was 73 and 79% (P=NS) for HIV-infected and non-HIV-infected recipients, respectively (Table 1) [[12]Ragni M.V. Belle S.H. Im K. Neff G. Roland M. Stock P. et al.Survival of human immunodeficiency virus-infected liver transplant recipients.J Infect Dis. 2003; 188: 1412-1420Crossref PubMed Scopus (198) Google Scholar]. Similar rates were seen for graft survival. Therefore, survival in HIV-infected recipients in the HAART period was almost 30% higher than in the pre-HAART era [8Tzakis A.G. Cooper M.H. Dummer J.S. Ragni M. Ward J.W. Starzl T.E. Transplantation in HIV+ patients.Transplantation. 1990; 49: 354-358Crossref PubMed Scopus (164) Google Scholar, 9Erice A. Rhame F.S. Heussner R.C. Dunn D.L. Balfour H.H. Human immunodeficiency virus infection in patients with solid-organ transplants: report of five cases and review.Rev Infect Dis. 1991; 13: 537-547Crossref PubMed Scopus (129) Google Scholar, 10Bouscarat F. Samuel D. Simon F. Debat P. Bismuth H. Saimot A.G. An observational study of 11 French liver transplant recipients infected with human immunodeficiency virus type 1.Clin Infect Dis. 1994; 19: 854-859Crossref PubMed Scopus (75) Google Scholar, 11Gordon F.H. Mistry P.K. Sabin C.A. Lee C.A. Outcome of orthotropic liver transplantation in patients with haemophilia.Gut. 1998; 42: 744-749Crossref PubMed Scopus (135) Google Scholar]. Therefore, at present, HIV infection is no longer a formal contraindication to transplant [[13]Policies & Bylaws. Alexandria, Va.: United Network for Organ Sharing; 2001 (http://www.unos.org/policiesandbylaws/bylaws.asp?resources=true) [as of 30th December, 2004].Google Scholar].Table 1Three-year survival of patients with and without HIV-infection who underwent liver transplantation before and during the HAART period 8Tzakis A.G. Cooper M.H. Dummer J.S. Ragni M. Ward J.W. Starzl T.E. Transplantation in HIV+ patients.Transplantation. 1990; 49: 354-358Crossref PubMed Scopus (164) Google Scholar, 10Bouscarat F. Samuel D. Simon F. Debat P. Bismuth H. Saimot A.G. An observational study of 11 French liver transplant recipients infected with human immunodeficiency virus type 1.Clin Infect Dis. 1994; 19: 854-859Crossref PubMed Scopus (75) Google Scholar, 11Gordon F.H. Mistry P.K. Sabin C.A. Lee C.A. Outcome of orthotropic liver transplantation in patients with haemophilia.Gut. 1998; 42: 744-749Crossref PubMed Scopus (135) Google Scholar, 12Ragni M.V. Belle S.H. Im K. Neff G. Roland M. Stock P. et al.Survival of human immunodeficiency virus-infected liver transplant recipients.J Infect Dis. 2003; 188: 1412-1420Crossref PubMed Scopus (198) Google ScholarBefore HAARTaData from Refs. [8,10,11]. (<1996)During HAART periodbData from Refs. [12]. (1996–2004)HIV-infected patients (no.=32) (%)HIV-infected patients (no.=24) (%)Non-HIV infected patients (UNOS) (no.=5225) (%)Survival1-year6987872-years5673823-years447379HAART, highly active antiretroviral therapy; UNOS, united network for organ sharing.a Data from Refs. 8Tzakis A.G. Cooper M.H. Dummer J.S. Ragni M. Ward J.W. Starzl T.E. Transplantation in HIV+ patients.Transplantation. 1990; 49: 354-358Crossref PubMed Scopus (164) Google Scholar, 10Bouscarat F. Samuel D. Simon F. Debat P. Bismuth H. Saimot A.G. An observational study of 11 French liver transplant recipients infected with human immunodeficiency virus type 1.Clin Infect Dis. 1994; 19: 854-859Crossref PubMed Scopus (75) Google Scholar, 11Gordon F.H. Mistry P.K. Sabin C.A. Lee C.A. Outcome of orthotropic liver transplantation in patients with haemophilia.Gut. 1998; 42: 744-749Crossref PubMed Scopus (135) Google Scholar.b Data from Refs. [12]Ragni M.V. Belle S.H. Im K. Neff G. Roland M. Stock P. et al.Survival of human immunodeficiency virus-infected liver transplant recipients.J Infect Dis. 2003; 188: 1412-1420Crossref PubMed Scopus (198) Google Scholar. Open table in a new tab In Spain, the OLT programme in HIV-infected patients started in January 2002 [[7]Miró J.M. Montejo M. Rufi G. Barcena R. Vargas V. Rimola A. et al.Liver transplantation in patients with HIV infection: a reality in 2004.Enferm Infecc Microbiol Clin. 2004; 22: 529-538PubMed Google Scholar]. Until February 2005, 35 liver transplantations were performed in 34 patients. 90% of patients were HCV–HIV co-infected. There were four deaths (11%) after a median follow-up of 14 months (3–36 months). One and 2-year survival rates (95% CI) were 90% (73–97%) and 83 (57–94%), respectively.3. Magnitude of the problem in EuropeAccording to current estimates, there are around 540,000 HIV-infected patients in Western European countries [[14]Hamers F.F. Downs A.M. The changing face of the HIV epidemic in western Europe: what are the implications for public health policies?.Lancet. 2004; 364: 83-94Abstract Full Text Full Text PDF PubMed Scopus (159) Google Scholar]. Prevalence of HCV and HBV co-infection in European HIV-infected patients was 33 and 9%, respectively [15Rockstroh J. Mocroft A. Soriano V. Tural C. Losso M. Horban A. et al.Influence of hepatitis C virus infection on HIV-1 disease progression and response to highly active antiretroviral therapy.J Infect Dis. 2005; 192: 992-1002Crossref PubMed Scopus (334) Google Scholar, 16Konopnicki D. Mocroft A. de Wit S. Antunes F. Ledergerber B. Katlama C. et al.Hepatitis B and HIV: prevalence, AIDS progression, response to highly active antiretroviral therapy and increased mortality in the EuroSIDA cohort.AIDS. 2005; 19: 593-601Crossref PubMed Scopus (416) Google Scholar]. So, the estimated number of HCV and HBV co-infected patients is around 180,000 and 49,000 cases, respectively. In a cross-sectional study performed in Spain [[17]González-García J.J. Mahillo B. Hernández S. Pacheco R. Diz S. García P. et al.Prevalences of hepatitis virus co-infection and indications for chronic hepatitis C virus treatment and liver transplantation in Spanish HIV-infected patients. The GESIDA 29/02 and FIPSE 12185/01 Multicenter Study.Enferm Infecc Microbiol Clin. 2005; 23: 340-348Crossref PubMed Scopus (67) Google Scholar], 8% of co-infected patients had clinical or histological criteria of cirrhosis and 17% of them met the Spanish criteria to be admitted in an OLT waiting list. Therefore, the potential number of candidates for OLT in Europe would be around 3100 cases.4. HIV criteria for including HIV-infected patients on the liver transplant waiting listMost liver transplant groups are using similar criteria in the HAART era [4Roland M.E. Stock P.G. Review of solid-organ transplantation in HIV-infected patients.Transplantation. 2003; 75: 425-429Crossref PubMed Scopus (123) Google Scholar, 5Fung J. Eghtesad B. Patel-Tom K. DeVera M. Chapman H. Ragni M. Liver transplantation in patients with HIV infection.Liver Transpl. 2004; 10: S39-S53Crossref PubMed Google Scholar, 6Neff G.W. Sherman K.E. Eghtesad B. Fung J. Review article: current status of liver transplantation in HIV-infected patients.Aliment Pharmacol Ther. 2004; 20: 993-1000Crossref PubMed Scopus (15) Google Scholar, 18O'Grady J. Taylor C. Brook G. Guidelines for liver transplantation in patients with HIV infection (2005).HIV Med. 2005; 6: 149-153Crossref PubMed Scopus (39) Google Scholar]. Criteria concerning the liver disease are the same as for the non-HIV-infected population. Inclusion and exclusion criteria have been recently reviewed in the English guidelines for liver transplantation [[18]O'Grady J. Taylor C. Brook G. Guidelines for liver transplantation in patients with HIV infection (2005).HIV Med. 2005; 6: 149-153Crossref PubMed Scopus (39) Google Scholar]. The main indication for OLT in HIV-infected patients being ESLD caused by HCV co-infection [4Roland M.E. Stock P.G. Review of solid-organ transplantation in HIV-infected patients.Transplantation. 2003; 75: 425-429Crossref PubMed Scopus (123) Google Scholar, 5Fung J. Eghtesad B. Patel-Tom K. DeVera M. Chapman H. Ragni M. Liver transplantation in patients with HIV infection.Liver Transpl. 2004; 10: S39-S53Crossref PubMed Google Scholar, 6Neff G.W. Sherman K.E. Eghtesad B. Fung J. Review article: current status of liver transplantation in HIV-infected patients.Aliment Pharmacol Ther. 2004; 20: 993-1000Crossref PubMed Scopus (15) Google Scholar]. Less frequent indications were HBV co-infection (either acute or ESLD) and liver cancer. Criteria concerning the HIV-infection, a multidisciplinary Spanish Task Force [[19]Miró J.M. Torre-Cisneros J. Moreno A. Tuset M. Querada C. Laguno M. et al.GESIDA/GESITRA-SEIMC, PNS and ONT consensus document on solid organ transplant (SOT) in HIV-infected patients in Spain—March, 2005.Enferm Infecc Microbiol Clin. 2005; 23: 353-362Crossref PubMed Scopus (80) Google Scholar] has recently defined clinical, immunological and virological criteria (see Table 2).Table 2Spanish HIV criteria for OLT in HIV infection [19]Miró J.M. Torre-Cisneros J. Moreno A. Tuset M. Querada C. Laguno M. et al.GESIDA/GESITRA-SEIMC, PNS and ONT consensus document on solid organ transplant (SOT) in HIV-infected patients in Spain—March, 2005.Enferm Infecc Microbiol Clin. 2005; 23: 353-362Crossref PubMed Scopus (80) Google ScholarA. HIV-infected patients who do not fulfil the criteria for HAART CD4 lymphocyte count >350 cells/ mm3B. HIV-infected patients who fulfil the criteria for HAART No AIDS-defining opportunistic infection except tuberculosis, oesophageal candidiasis or P. jirovecii pneumonia Must have a CD4 lymphocyte count >100 cells/mm3aPatients who have suffered from tuberculosis, oesophageal candidiasis or P. jirovecii pneumonia, must have a CD4 lymphocyte count of >200cells/mm3. Undetectable viral load in plasma (HIV-1 RNA) (<50 copies/ml) at the time of the transplant or effective and durable therapeutic options for HIV infection during the post-transplant periodC. Other criteria and criteria related to risk behaviour: Abstinence from drugs (heroin, cocaine) for at least 2 years No consumption of alcohol for at least 6 months Favourable psychological/psychiatric evaluation Understanding of the techniques and responsibilities involved in OLT Social stability Women must not be pregnantPatients already included on a waiting list for OLT who no longer fulfil the previously mentioned criteria are temporarily excluded and re-included when they fulfil the criteria again. HAART, highly active antiretroviral therapy; OLT, orthotopic liver transplantation.a Patients who have suffered from tuberculosis, oesophageal candidiasis or P. jirovecii pneumonia, must have a CD4 lymphocyte count of >200 cells/mm3. Open table in a new tab 4.1 Clinical criteriaIdeally, patients should not have suffered previously from AIDS-defining diseases, as they may have a greater risk of reactivation. However, the improved prognosis post-HAART means that some authors are in favour of withdrawing exclusion criteria for some opportunistic infections which can be efficaciously treated and prevented, such as tuberculosis, candidiasis and Pneumocystis jirovecii pneumonia [4Roland M.E. Stock P.G. Review of solid-organ transplantation in HIV-infected patients.Transplantation. 2003; 75: 425-429Crossref PubMed Scopus (123) Google Scholar, 6Neff G.W. Sherman K.E. Eghtesad B. Fung J. Review article: current status of liver transplantation in HIV-infected patients.Aliment Pharmacol Ther. 2004; 20: 993-1000Crossref PubMed Scopus (15) Google Scholar, 20Roland M.E. Havlir D.V. Responding to organ failure in HIV-infected patients.N Engl Med. 2003; 348: 2279-2281Crossref PubMed Scopus (35) Google Scholar].The Spanish Task Force considered that the experience with other HIV-infected opportunistic infections and tumours (like Kaposi sarcoma) is still too limited to make any recommendations.4.2 Immunological criteriaAll groups have agreed that the CD4+lymphocyte count should be above 100 cells/mm3 for OLT [4Roland M.E. Stock P.G. Review of solid-organ transplantation in HIV-infected patients.Transplantation. 2003; 75: 425-429Crossref PubMed Scopus (123) Google Scholar, 5Fung J. Eghtesad B. Patel-Tom K. DeVera M. Chapman H. Ragni M. Liver transplantation in patients with HIV infection.Liver Transpl. 2004; 10: S39-S53Crossref PubMed Google Scholar, 6Neff G.W. Sherman K.E. Eghtesad B. Fung J. Review article: current status of liver transplantation in HIV-infected patients.Aliment Pharmacol Ther. 2004; 20: 993-1000Crossref PubMed Scopus (15) Google Scholar, 19Miró J.M. Torre-Cisneros J. Moreno A. Tuset M. Querada C. Laguno M. et al.GESIDA/GESITRA-SEIMC, PNS and ONT consensus document on solid organ transplant (SOT) in HIV-infected patients in Spain—March, 2005.Enferm Infecc Microbiol Clin. 2005; 23: 353-362Crossref PubMed Scopus (80) Google Scholar]. This figure is lower than used for kidney transplantation (e.g. CD4>200 cells/mm3) because patients with cirrhosis often have lymphopenia due to hypersplenism, which leads to a lower absolute CD4+count, despite high CD4 percentages and good virological control of HIV.4.3 Virological criteriaThe essential criteria for OLT is that the patient must be able to undergo effective and long-lasting antiretroviral therapy during the post-transplant period [4Roland M.E. Stock P.G. Review of solid-organ transplantation in HIV-infected patients.Transplantation. 2003; 75: 425-429Crossref PubMed Scopus (123) Google Scholar, 5Fung J. Eghtesad B. Patel-Tom K. DeVera M. Chapman H. Ragni M. Liver transplantation in patients with HIV infection.Liver Transpl. 2004; 10: S39-S53Crossref PubMed Google Scholar, 6Neff G.W. Sherman K.E. Eghtesad B. Fung J. Review article: current status of liver transplantation in HIV-infected patients.Aliment Pharmacol Ther. 2004; 20: 993-1000Crossref PubMed Scopus (15) Google Scholar, 19Miró J.M. Torre-Cisneros J. Moreno A. Tuset M. Querada C. Laguno M. et al.GESIDA/GESITRA-SEIMC, PNS and ONT consensus document on solid organ transplant (SOT) in HIV-infected patients in Spain—March, 2005.Enferm Infecc Microbiol Clin. 2005; 23: 353-362Crossref PubMed Scopus (80) Google Scholar]. The ideal situation is one in which the patient tolerates HAART before transplant and is ready for the transplant with undetectable plasma HIV viral load by ultra-sensitive techniques (<50 copies/ml). However, some patients remain viraemic with HAART. In these cases, it is mandatory to carry out antiretroviral sensitivity testing (genotypic or phenotypic resistance testing) [[21]Hirsch M.S. Brun-Vezinet F. Clotet B. Conway B. Kuritzkes D.R. D'Aquila R.T. et al.Antiretroviral drug resistance testing in adults infected with human immunodeficiency virus type 1: 2003 recommendations of an International AIDS Society-USA Panel.Clin Infect Dis. 2003; 37: 113-128Crossref PubMed Scopus (474) Google Scholar] to ascertain the real therapeutic options.Furthermore, to include an HIV-infected patient on the OLT waiting list, the candidate must have a favourable psychiatric evaluation. Patients who actively consume drugs will be excluded. In Spain, it is recommended a consumption-free period of 2 years for heroin and cocaine [[19]Miró J.M. Torre-Cisneros J. Moreno A. Tuset M. Querada C. Laguno M. et al.GESIDA/GESITRA-SEIMC, PNS and ONT consensus document on solid organ transplant (SOT) in HIV-infected patients in Spain—March, 2005.Enferm Infecc Microbiol Clin. 2005; 23: 353-362Crossref PubMed Scopus (80) Google Scholar] and 6 months without addiction for other drugs (e.g. alcohol). Patients who are on stable methadone maintenance programmes are not excluded from transplant and can continue on such programmes after the transplant [[22]Liu L.U. Schiano T.D. Lau N. O'Rourke M. Min A.D. Sigal S.H. et al.Survival and risk of recidivism in methadone-dependent patients undergoing liver transplantation.Am J Transplant. 2003; 3: 1273-1277Crossref PubMed Scopus (49) Google Scholar]. Finally, HIV-infected patients must show an appropriate degree of social stability to ensure adequate care in the post-transplant period.5. Special considerations in HIV-infected patientsOLT in HIV-infected patients is a complex scenario that requires a multidisciplinary approach during the pre- and post-transplant periods [4Roland M.E. Stock P.G. Review of solid-organ transplantation in HIV-infected patients.Transplantation. 2003; 75: 425-429Crossref PubMed Scopus (123) Google Scholar, 5Fung J. Eghtesad B. Patel-Tom K. DeVera M. Chapman H. Ragni M. Liver transplantation in patients with HIV infection.Liver Transpl. 2004; 10: S39-S53Crossref PubMed Google Scholar, 6Neff G.W. Sherman K.E. Eghtesad B. Fung J. Review article: current status of liver transplantation in HIV-infected patients.Aliment Pharmacol Ther. 2004; 20: 993-1000Crossref PubMed Scopus (15) Google Scholar, 19Miró J.M. Torre-Cisneros J. Moreno A. Tuset M. Querada C. Laguno M. et al.GESIDA/GESITRA-SEIMC, PNS and ONT consensus document on solid organ transplant (SOT) in HIV-infected patients in Spain—March, 2005.Enferm Infecc Microbiol Clin. 2005; 23: 353-362Crossref PubMed Scopus (80) Google Scholar]. The team should include members from the liver transplant team (medical and surgical), infectious diseases and HIV specialists, a psychologist/psychiatrist, an expert on alcoholism and drug abuse, and a social worker.5.1 Controversial issues in the pre-transplant periodWaiting list mortality in HIV-infected patients with ESLD is very high. This is because survival of HIV-infected patients with decompensated cirrhosis is much lower than in HIV-negative patients [[23]Miró JM, Blanco JL, Rimola A, Grande L, Moreno A, Mestre G, et al. Evolution of HIV-1 infection and liver disease in HIV-1-Infected patients with End-Stage Liver Disease (ESLD) who might be potential candidates for liver transplantation. In: 8th conference on retroviruses and opportunistic infections, Chicago, IL; 2001. Abstract 577.Google Scholar]. Pineda et al. [[24]Pineda J.A. Romero-Gomez M. Diaz-Garcia F. Giron-Gonzalez J.A. Montero J.L. Torre-Cisneros J. et al.HIV co-infection shortens the survival of patients with hepatitis C virus-related decompensated cirrhosis.Hepatology. 2005; 41: 779-789Crossref PubMed Scopus (244) Google Scholar] have recently shown in a multicentre case-control study performed in Spain that the outcome of cirrhosis after the first decompensation in HIV–HCV co-infected patients is much worse than in the mono HCV-infected population. Survival at 1, 2 and 5 years for co-infected and mono-infected populations was 54%/74%, 40%/61% and 25%/44%, respectively [[24]Pineda J.A. Romero-Gomez M. Diaz-Garcia F. Giron-Gonzalez J.A. Montero J.L. Torre-Cisneros J. et al.HIV co-infection shortens the survival of patients with hepatitis C virus-related decompensated cirrhosis.Hepatology. 2005; 41: 779-789Crossref PubMed Scopus (244) Google Scholar].For this reason, these patients should be evaluated for OLT after the first clinical decompensation of the liver disease: ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, gastroesophageal variceal bleeding, jaundice and/or hepatocellular carcinoma. Both, prevention and effective treatment of these complications may improve the likelihood of patient survival until OLT [25Cardenas A. Gines P. Management of complications of cirrhosis in patients awaiting liver transplantation.J Hepatol. 2005; 42: S124-S133Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar, 26Llovet J.M. Fuster J. Bruix J. Barcelona-Clinic Liver Cancer Group. The Barcelona approach: diagnosis, staging, and treatment of hepatocellular carcinoma.Liver Transpl. 2004; 10: S115-S120Crossref PubMed Scopus (575) Google Scholar].On the other hand, organ transplantation in HIV-infected patients have raised ethical problems which have not yet been completely resolved. However, currently most groups agree that HIV-infected patients should receive the same treatment as other patients and be included on waiting lists under the same conditions [[27]Roland M.E. Bernard L. Braff J. Stock P.G. 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. 2003; 163: 1773-1778Crossref PubMed Scopus (33) Google Scholar].The pre-transplant evaluation of donor and recipients should be the same as for non-HIV-infected patients. With respect to the type of donor to be used in HIV-infected patients, most solid organ transplants were carried out using cadaveric donors [4Roland M.E. Stock P.G. Review of solid-organ transplantation in HIV-infected patients.Transplantation. 2003; 75: 425-429Crossref PubMed Scopus (123) Google Scholar, 5Fung J. Eghtesad B. Patel-Tom K. DeVera M. Chapman H. Ragni M. Liver transplantation in patients with HIV infection.Liver Transpl. 2004; 10: S39-S53Crossref PubMed Google Scholar, 6Neff G.W. Sherman K.E. Eghtesad B. Fung J. Review article: current status of liver transplantation in HIV-infected patients.Aliment Pharmacol Ther. 2004; 20: 993-1000Crossref PubMed Scopus (15) Google Scholar, 7Miró J.M. Montejo M. Rufi G. Barcena R. Vargas V. Rimola A. et al.Liver transplantation in patients with HIV infection: a reality in 2004.Enferm Infecc Microbiol Clin. 2004; 22: 529-538PubMed Google Scholar]. In recent years, and as a consequence of the increased demand for organs, the number of living donors has increased. Nevertheless, the benefits of this technique have yet to be demonstrated in the HIV-infected population.5.2 Issues to consider in the post-transplant periodAfter OLT, patients and physicians start a new and complex clinical situa