Epidemiology and outcome of infections in human immunodeficiency virus/hepatitis C virus-coinfected liver transplant recipients: a FIPSE/GESIDA prospective cohort study.

Information about infections unrelated to acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus (HIV)-infected liver recipients is scarce. The aims of this study were to describe the prevalence, clinical characteristics, time of onset, and outcomes of bacterial, viral, and fungal infections in HIV/hepatitis C virus (HCV)-coinfected orthotopic liver transplant recipients and to identify risk factors for developing severe infections. We studied 84 consecutive HIV/HCV-coinfected patients who underwent liver transplantation at 17 sites in Spain between 2002 and 2006 and were followed until December 2009. The median age was 42 years, and 76% were men. The median follow-up was 2.6 years (interquartile range = 1.25-3.53 years), and 54 recipients (64%) developed at least 1 infection. Thirty-eight (45%) patients had bacterial infections, 21 (25%) had cytomegalovirus (CMV) infections (2 had CMV disease), 13 (15%) had herpes simplex virus infections, and 16 (19%) had fungal infections (7 cases were invasive). Nine patients (11%) developed 10 opportunistic infections with a 44% mortality rate. Forty-three of 119 infectious episodes (36%) occurred in the first month after transplantation, and 53 (45%) occurred after the sixth month. Thirty-six patients (43%) had severe infections. Overall, 36 patients (43%) died, and the deaths were related to severe infections in 7 cases (19%). Severe infections increased the mortality rate almost 3-fold [hazard ratio (HR) = 2.9, 95% confidence interval (CI) = 1.5-5.8]. Independent factors for severe infections included a pretransplant Model for End-Stage Liver Disease (MELD) score >15 (HR = 3.5, 95% CI = 1.70-7.1), a history of AIDS-defining events before transplantation (HR = 4.0, 95% CI = 1.9-8.6), and non-tacrolimus-based immunosuppression (HR = 2.5, 95% CI = 1.3-4.8). In conclusion, the rates of severe and opportunistic infections are high in HIV/HCV-coinfected liver recipients and especially in those with a history of AIDS, a high MELD score, or non-tacrolimus-based immunosuppression.

The model for end-stage liver disease score is the best prognostic factor in human immunodeficiency virus 1-infected patients with end-stage liver disease: a prospective cohort study.

End-stage liver disease (ESLD) has become the main cause of mortality in patients coinfected by human immunodeficiency virus (HIV) and hepatitis B virus or hepatitis C virus in developed countries. The aim of this study was to describe the natural history of and prognostic factors for ESLD, with particular attention paid to features affecting liver transplantation. This was a prospective cohort study in 2 Spanish community-based hospitals performed between 1999 and 2004. One hundred four consecutive patients with cirrhosis and a first clinical decompensation of their chronic liver disease or hepatocellular carcinoma were included in the study. During a median follow-up of 10 months (endpoint: death, liver transplantation, or the last checkup date), 61 patients (59%) died. The probability of mortality (Kaplan-Meier method) at 1, 2, and 3 years was 43% [95% confidence interval (CI), 34%-60%], 59% (95% CI, 48%-70%), and 70% (95% Cl, 59%-81%), respectively. In a multivariate analysis, the Model for End-Stage Liver Disease (MELD) score and the inability to reach an undetectable plasma HIV-1 RNA viral load at any time during follow-up were the only variables independently associated with the risk of death (P < 0.001). Fifteen (14%) of the 104 patients were accepted for liver transplantation, although only 5 underwent the procedure, and 10 died while on the waiting list. The waiting list mortality rate in patients with a MELD score < 20 and in patients with a MELD score >20 was 58% and 100%, respectively (median follow-up, 5 months). In conclusion, HIV-1-infected patients with ESLD, especially those with poorly controlled HIV and a high MELD score, have a poor short-term outcome. The MELD score may be useful in deciding whether to indicate liver transplantation in these patients. However, because only a small proportion of the patients in this study were considered candidates for liver transplantation and most died while on the waiting list, few received a transplant.

Liver transplantation in HIV/hepatitis co-infection.

The prognosis of HIV infection has dramatically improved in recent years with the introduction of combined antiretroviral therapy. Currently, liver disease is one of the most important causes of morbidity and mortality, even more so given the high rate of hepatitis C virus co-infection in countries where drug abuse has been an important HIV risk factor. Survival of HIV-co-infected patients with end-stage liver disease (ESLD) is poor and shorter than that of the non-HIV-infected population. One-year survival of HIV-infected patients with ESLD is only around 50-55%. HIV infection is no longer a contraindication to transplantation, which is becoming a standard therapy in most developed countries. The HIV criteria used to select HIV-infected patients for liver transplantation are quite similar in Europe and North America. Current criteria state that having had an opportunistic infection (e.g. tuberculosis, candidiasis, PCP) is not a strict exclusion criterion. However, patients must have a CD4 count above 100 cells/mm3 and a plasma HIV-1 RNA viral load that is suppressible with antiretroviral treatment. More than 200 orthotopic liver transplants (OLT) in HIV-infected patients have been published in recent years and the mid-term (3-year) survival was similar to that of HIV-negative patients. The main problems in the post-transplantation period are the pharmacokinetic and pharmacodynamic interactions between antiretroviral and immunosuppressive agents and the recurrence of HCV infection, which is the principal cause of post-transplantation mortality. There are controversial results regarding mid-term survival of HIV-HCV co-infected patients compared with HCV mono-infected patients. However, one study showed a trend of poorer 5-year survival of HIV-HCV co-infected patients. There is little experience with the treatment of recurrent HCV infection. Preliminary studies showed rates of sustained virological response ranging between 15% and 20% in HIV-HCV co-infected recipients. Liver transplantation in HIV-HBV co-infected patients had a good prognosis because HBV recurrence can be successfully prevented using immunoglobulins and anti-HBV drugs. Finally, this field is evolving continuously and the indications for liver transplantation or the management of HCV co-infection may change in the future as more evidence becomes available.

Management of end-stage liver disease in HIV-infected patients.

PURPOSE OF REVIEW: This review provides information on the natural history of end-stage liver disease in HIV/hepatitis C virus-coinfected patients from diagnosis to liver transplantation or death and summarizes recent developments in the epidemiology, management, and prognosis of end-stage liver disease and orthotopic liver transplantation in this population compared with the HIV-negative population. RECENT FINDINGS: Many studies have described epidemiological aspects, including the increasing incidence of end-stage liver disease, as a cause of non-AIDS-related death in the co-infected population in developed countries, whereas other reports have focused on the clinical presentation and prognosis of end-stage liver disease in this specific clinical setting. The medical management of end-stage liver disease should be the same as for the HIV-negative population, and orthotopic liver transplantation is the only therapeutic option for HIV-infected patients who are eligible for this procedure. SUMMARY: End-stage liver disease is becoming a major issue in the HIV/HCV-coinfected population because of its increasing frequency, especially now the prognosis of HIV infection has improved with combined antiretroviral therapy. Medical management is essential and should be considered a bridge to orthotopic liver transplantation. Nevertheless, many issues remain unclear and must be examined in further studies.

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/mm(3), 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.

[GESIDA/GESITRA-SEIMC, PNS and ONT consensus document on solid organ transplant (SOT) in HIV-infected patients in Spain (March, 2005)]. / Documento de consenso GESIDA/GESITRA-SEIMC, SPNS y ONT sobre trasplante de órgano sólido en pacientes infectados por el VIH en España (marzo 2005).

Solid organ transplant may be the only therapeutic alternative in some HIV-infected patients. Experience in North America and Europe during the last five years shows that survival at three years after an organ transplant is similar to that observed in HIV-negative patients. The criteria agreed upon to select HIV patients for transplant are: no opportunistic infections (except tuberculosis, oesophageal candidiasis or P. jiroveci -previously carinii- pneumonia), CD4 lymphocyte count above 200 cells/.L (100 cells/.L in the case of liver transplant) and an HIV viral load which is undetectable or suppressible with antiretroviral therapy. Another criterion is a two-year abstinence from heroin and cocaine, although the patient may be in a methadone programme. The main problems in the post-transplant period are pharmacokinetic and pharmacodynamic interactions between antiretorivirals and immunosuppressors, rejection and the management of relapse of HCV infection, which is one of the main causes of post-liver transplant mortality. Up to now, experience with pegylated interferon and ribavirin is scarce in this population. The English version of the manuscript is available at http://www.gesidaseimc.com.

Preconditioning protects liver and lung damage in rat liver transplantation: role of xanthine/xanthine oxidase.

This study was designed to evaluate whether ischemic preconditioning could confer protection against liver and lung damage associated with liver transplantation. The effect of preconditioning on the xanthine/xanthine oxidase (XOD) system in liver grafts subjected to 8 and 16 hours of cold ischemia was also evaluated. Increased xanthine levels and marked conversion of xanthine dehydrogenase (XDH) to XOD were observed after hepatic cold ischemia. Xanthine/XOD could play a role in the liver and lung damage associated with liver transplantation. This assumption is based on the observation that inhibition of XOD reduced postischemic reactive oxygen species (ROS) generation and hepatic injury as well as ensuing lung inflammatory damage, including neutrophil accumulation, oxidative stress, and edema formation. Ischemic preconditioning reduced xanthine accumulation and conversion of XDH to XOD in liver grafts during cold ischemia. This could diminish liver and lung damage following liver transplantation. In the liver, preconditioning prevented postischemic ROS generation and hepatic injury as well as the injurious effects in the lung following liver transplantation. Administration of xanthine and XOD to preconditioned rats led to hepatic ROS and transaminase levels similar to those found after reperfusion and abolished the protective effect of preconditioning on the lung inflammatory damage. In conclusion, ischemic preconditioning reduces both liver and lung damage following liver transplantation. This endogenous protective mechanism is capable of blocking xanthine/XOD generation in liver grafts during cold ischemia.

[Liver transplantation in patients with HIV infection: a reality in 2004]. / Trasplante hepático en pacientes con infección por el VIH: una realidad en el año 2004.

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.

Trasplante hepático en pacientes infectados por el VIH-1 / Liver Transplantation in HIV-1 infected patients

Actualmente la enfermedad hepática es una de las causas más importantes de morbilidad y mortalidad en los pacientes con infección por VIH. La supervivencia de los pacientes con enfermedad hepática terminal es más corta comparada con la de las personas no infectadas. La infección por VIH ha dejado de ser una contraindicación para el trasplante de órganos sólidos...

Currently, liver disease is one of the most important cause of morbidity and mortality in HIV-1 infected patients. Survival of HIV-coinfected patients with end-stage liver disease (ESLD) is poor and shorter than that of the non-HIV-infected population. HIV infections is no longer a contraindication to solid organ transplantation...

Priorización en la lista de espera para trasplante / No disponible

No disponible

Documento de consenso GESIDA/GESITRA-SEIMC, SPNS y ONT sobre trasplante de órgano sólido en pacientes infectados por el VIH en España (marzo 2005) / Consensus document from GESIDA/GESITRA-SIMC, SPNS and ONT on solid organ transplantation in patients with HIV infection in Spain (March 2005)

El trasplante de órgano sólido puede ser la única alternativa terapéutica en ciertos pacientes infectados por el virus de la inmunodeficiencia humana (VIH). La experiencia acumulada en América del Norte y Europa en los últimos 5 años indica que la supervivencia a los 3 años del trasplante de órgano sólido es similar a la de los pacientes no infectados por el VIH. Los criterios consensuados para seleccionar a los pacientes infectados por el VIH con indicación de trasplante son: no haber tenido infecciones oportunistas (a excepción de la tuberculosis, candidiasis esofágica o neumonía por Pneumocystis jiroveci ­antes carinii­), tener una cifra de linfocitos CD4 > 200 cél./μl (100 cél./μl en el caso del trasplante hepático) y una carga viral del VIH indetectable o suprimible con tratamiento antirretroviral. También se exige una abstinencia a la heroína y cocaína de 2 años de duración, pudiendo estar el paciente en programa de metadona. Los principales problemas del período postrasplante son las interacciones farmacocinéticas y farmacodinámicas entre los antirretrovirales y los inmunosupresores, el rechazo y la posibilidad de que la recidiva de la infección por el virus de la hepatitis C (VHC), que es una de las principales causas de mortalidad postrasplante hepático, siga una evolución peor. La experiencia del tratamiento con interferón pegilado y ribavirina es escasa en esta población hasta el momento actual (AU)

Solid organ transplantation may be the only therapeutic option for some human inmunodeficience virus (HIV)-infected patients. Experience in North America and Europe over the last five years has shown that three-year survival of these patients following organ transplantation is similar to that of HIV-negative patients. The consensus criteria for the selection of HIV patients for transplantation include the following: no opportunistic infections (except tuberculosis, esophageal candidiasis or Pneumocystis jiroveci ­ previously carinii ­ pneumonia), CD4 lymphocyte count above 200 cells/μl (100 cells/μl in the case of liver transplantation) and HIV viral load that is undetectable or suppressible with antiretroviral therapy. Also required is a two-year abstinence from heroin and cocaine, although the patient may be in a methadone program. The main problems in the post-transplantation period in these patients are pharmacokinetic and pharmacodynamic interactions between antiretorivirals and immunosuppressors, rejection, and the fact that the risk of relapsed HCV infection is exacerbated, and this is one of the main causes of post-liver transplantation (..) (AU)