Tenth Forum on Liver Transplantation Are HIV-infected patients ...

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Rainer Weber, from the University of Zü rich, Switzer- land, covers ... Dr. Stock presents the criteria to optimally select patients ... Clichy or King's College criteria,.
Journal of Hepatology 48 (2008) 695–696 www.elsevier.com/locate/jhep

Editorial

Tenth Forum on Liver Transplantation Are HIV-infected patients candidates for liver transplantation? q Pierre-Alain Clavien* Swiss HPB (Hepato-Pancreato-Biliary) Center, Department of Surgery, University Hospital Zu¨rich, Raemistrasse 100, CH-8091 Zu¨rich, Switzerland

Since 2005, we have published a series of ‘‘Forum on Liver Transplantation” covering a number of controversial topics ranging from issues related to hepatitis C [1], cancer [2–4], surgical aspects including the use of living [5] or ‘‘marginal” [6] donors, acute liver failure [7] or even on issues related to the best institutional setting providing an optimal framework, e.g., center approach, to treat patients with liver diseases [8]. Each forum was comprised of a series of 4–5 articles, in which established experts were selected to address a specific question on a controversial topic. Starting from the 10th forum, we will switch to a different format, whereby an expert (first author) will be responsible for a single article to coordinate the entire forum, with international colleagues chosen based on their scientific contribution to the field. In contrast to many other reviews, co-authorship with junior members in this new format will be avoided to present a ‘‘Forum” based on the sole opinion of ‘‘established” experts. Forum 10, the first one of this new format, has been prepared by Didier Samuel, from Paul Brousse Hospital, Paris, whose task involved addressing the controversial issues of liver transplantation in the HIV-infected population. The topic is very timely due to the increasing prevalence of co-infection with hepatitis viruses B q The author declares that he does not have anything to disclose regarding funding from industries or conflict of interest with respect to this manuscript. * Tel.: +41 1 2552300; fax: +41 1 2554449. E-mail address: [email protected]. Abbreviations: AIDS, acquired immunodeficiency syndrome; MELD, model for end-stage liver disease; OLT, orthotopic liver transplantation; HIV, human immunodeficiency virus; IFN, interferon; NIH, National Institute of Health; HBV, hepatitis B virus; HCV, hepatitis C virus; DNA, deoxyribonucleic acid.

and C, the advent of new antiviral strategies, both against HIV and hepatitis B and C, and the increasing panel of available anti-rejection drugs after transplantation. Recent reports in this field justified this discussion with the aim to also highlight areas requiring further investigation. Rainer Weber, from the University of Zu¨rich, Switzerland, covers the epidemiology of the 32 millions of HIVinfected patients worldwide, highlighting that the search for a vaccine has failed so far, and that, unfortunately, there is still no credible expectation about when one will become available [9]. In a large cohort of patients, the most frequent cause of non-AIDS related deaths in this population was liver disease, related in more than threequarters of cases to chronic hepatitis B and C co-infection [10]. Peter Stock from the University of California in San Francisco, USA, is the principal investigator of a large NIH sponsored study on the role of liver transplantation in HIV-infected patients. In a comprehensive discussion, Dr. Stock presents the criteria to optimally select patients for liver transplantation. Rigid rules such as a CD4+ counts >200 cell/mL should be avoided, as the presence of portal hypertension with hypersplenism and the use of IFN therapy in HCV-infected patients may cause further decreases in CD4+ counts, unrelated to HIV infection [11]. Similarly, opportunistic infection, once considered as an absolute contraindication, must be evaluated in light of the chance for the patient to reconstitute an immune response with antiretroviral therapies and appropriate antibiotic treatment. On the other hand, care should be taken to avoid transplantation in a patient with very poor liver reserve, i.e., high MELD score, particularly in the HCV population. At this point, the single most important factor in dealing with these complex patients is

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Forum on Liver Transplantation / Journal of Hepatology 48 (2008) 695–696

the availability of a clinician experienced with the HIV positive population. Another controversial issue is the choice of the immunosuppressive regimen following OLT. This part, covered by Jean-Charles Duclos-Valle´e, indicates that not much convincing data are currently available in this area. Two principles should, perhaps, trigger special attention: first, the avoidance of a rapid withdrawal of steroids [12], particularly in the HCV population, due to the evidence of accelerated fibrosis, and second, great care should be taken in managing potential interaction among antiviral and immunosuppressive drugs. Finally, Norah Terrault, from the University of California in San Francisco, USA, provides an excellent discussion related to the management of such patients before and after OLT. She emphasises the need for the early referral of co-infected HIV patients with hepatitis viruses B and C to transplant centers, as the severity of the disease and the nature of liver decompensation mostly influence the results of OLT in this population [13]. In HBV patients, the main pre-transplant strategy is to reach a low level of HBV DNA at the time of surgery, and in HCV patients, to prevent the rapid aggravation of the liver function (e.g. child C or high MELD score), which could be achieved, for example, by using a living donor. I thank Didier Samuel for the excellent and critical coverage of this complex field with the help of international experts. I hope that this new format will help clinicians to better evaluate this difficult population of patients for OLT. References [1] Berenguer M. What determines the natural history of recurrent hepatitis C after liver transplantation? [Second Forum on Liver Transplantation] J Hepatol 2005;42:447–479.

[2] Clavien P-A. Hepatocellular carcinoma: where are the controversies? [Editorial: Forum on Liver Transplantation] J Hepatol 2005;42:556–557. [3] Sanchez W, Talwalkar JA, Gores JG. Will all liver transplantation patients eventually die from cancer? [Fifth Forum on Liver Transplantation] J Hepatol 2006;44:13–18. [4] Clavien P-A. Is there a place for liver transplantation for ‘‘non HCC” tumors? [Editorial: Ninth Forum on Liver Transplantation] J Hepatol 2007;47:454–455. [5] Tan HP, Patel-Tom K, Marcos A. Adult living donor liver transplantation: who is the ideal donor and recipient? [Third Forum on Liver Transplantation] J Hepatol 2005;43:13–17. [6] Merion RM, Goodrich NP, Feng S. How can we define expanded criteria for liver donors? [Seventh Forum on Liver Transplantation] J Hepatol 2006;45:484–488. [7] Renner EL. How to decide when to list a patient with acute liver failure for liver transplantation? Clichy or King’s College criteria, or something else? [Eighth Forum on Liver Transplantation] J Hepatol 2007;46:554–557. [8] Clavien P-A, Mu¨llhaupt B, Pestalozzi BC. Do we need a center approach to treat patients with liver diseases? [Sixth Forum on Liver Diseases] J Hepatol 2006;44:639–642. [9] Steinbrook R. One step forward, two steps back – will there ever be an AIDS vaccine? N Engl J Med 2007;357:2653–2655. [10] Weber R, Sabin CA, Friis-Moller N, Reis P, El-Sadr WM, Kirk O, et al. Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study. Arch Intern Med 2006;166:132–141. [11] Ragni MV, Belle SH, 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. [12] Berenguer M, Royuela A, Zamora J. Immunosuppression with calcineurin inhibitors with respect to the outcome of HCV recurrence after liver transplantation: results of a meta-analysis. Liver Transplant 2007;13:21–29. [13] Pineda JA, Romero-Gomez M, Diaz-Garcia F, Giron-Gonzalez JA, Montero JL, Torre-Cisneros J, et al. HIV coinfection shortens the survival of patients with hepatitis C virus-related decompensated cirrhosis. Hepatology 2005;41:779–789.