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

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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.

Introduction

End-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]. 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]. 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 [3], [4], [5], [6], [7]. 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.

Section snippets

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 [8], [9], [10], [11], 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.

Magnitude of the problem in Europe

According to current estimates, there are around 540,000 HIV-infected patients in Western European countries [14]. Prevalence of HCV and HBV co-infection in European HIV-infected patients was 33 and 9%, respectively [15], [16]. 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], 8% of co-infected patients had clinical or histological criteria of cirrhosis and 17% of them met the

HIV criteria for including HIV-infected patients on the liver transplant waiting list

Most liver transplant groups are using similar criteria in the HAART era [4], [5], [6], [18]. 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]. The main indication for OLT in HIV-infected patients being ESLD caused by HCV co-infection [4], [5], [6]. Less frequent indications were HBV co-infection (either acute or ESLD) and liver cancer.

Special considerations in HIV-infected patients

OLT in HIV-infected patients is a complex scenario that requires a multidisciplinary approach during the pre- and post-transplant periods [4], [5], [6], [19]. 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.

Future research needs

There are several issues that should be explored in the future: (1) since survival is much shorter in HIV-co-infected patients, strategies to make OLT available sooner after patient assignment to this procedure should be underlined; (2) it is important to create a European or an International registry of cases, using standardized CRF in order to know the mid and long-term survival of OLT in HIV-infected patients and to compare it with the non-HIV-infected population; (3) to improve the

Acknowledgements

This document is dedicated to all our patients and has come about thanks to the collaboration of many people and institutions.

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