- Email: [email protected]
HCV infected liver graft
Journal of Hepatology 39 (2003) 1103–1104 www.elsevier.com/locate/jhep
BEYOND THE JOURNAL Associate Editors: Guadalupe Garcia-Tsao and Ronald Oude Elferink Committee: James Boyer, Jean-Franc¸ois Dufour, Hartmut Jaeschke, Luigi Pagliaro, Jorge Rakela, Tania Roskams and Christian Trautwein
HCV infected liver graft
Shortage of grafts is a major limitation of liver transplantation leading to the use of marginal liver grafts. Previous retrospective studies have suggested that antihepatitis C virus (HCV) positive recipients could be given liver grafts harvested in anti-HCV positive donors without detrimental influence on graft function and survival [1 – 4]. One study [1] reported that chronic coinfection by donor’s and recipient’s strain was infrequent. Each strain had the same probability to predominate as shown in the paper of Fan et al. The takeover of one strain seemed to be complete and long lasting [5]. Very interestingly, it was suggested that when donor’s strain predominate, the severity of recurrence was less severe. Fan et al. paper confirmed that the strain from the donor became predominant in around half of the cases. This is very important to consider since the resistance to interferon is not similar among different genotypes. For that reason and for recipients infected with genotypes 2 or 3, donor’s genotype should be ideally determined in order to avoid superinfection by HCV genotype 1. This clinical setting is an unique opportunity to study the coinfection by two different strains of HCV in humans. It is far to be an academic issue since it appears that multiple infections are frequent events in drug users who are highly exposed to repeated infections [6]. Classically, when two strains of a single strand positive RNA viruses compete in an individual, one strain became predominant due to its higher fitness, thus explaining that chronic coinfection is a rather infrequent event during infection by HCV. Predominance of one strain is also the rule in this study as well as in the larger Vargas’ study [1]. The possibility of recombination between strains belonging to different taxonomic genotypes as been reported for HCV [7]. This could be a major limitation of the use of livers harvested in HCV-positive patients due to the potential risk of emergence of a new strain at risk for the community and not only for the recipient. However, this risk seems mostly
theoretical since in important population of IV drug users, multiples challenges are frequent [6]. No recombinant strain has been observed in the paper of Fan et al. Although the number of cases is limited (n ¼ 6), these findings are encouraging, showing that the possibility of emergence of recombinant HCV strain, if any, is probably low. On a practical point of view, what to do? The use of antiHCV positive recipients is forbidden in France for instance while it seems a relatively frequent procedure in USA. Should we propose anti-HCV positive recipients to receive graft from anti-HCV positive recipients? Ideally, informed anti-HCV positive recipients should receive a graft with almost normal histology, which has been harvested in recipient infected with a compatible genotype. This will require, in the emergency setting of liver transplantation, extemporaneous liver histology and rapid determination of recipient’s genotype. Furthermore, those recipients should have a precise virological follow-up in order to detect the possibility of viral recombinants. This follow-up is technically feasible but remains extremely heavy and costly. Retrospective clinical and virological studies seems now sufficient to encourage the use of such livers. Finally, the highly probable development of future active antiviral drugs against HCV should facilitate the use of such marginal liver grafts and help to increase the total pool of liver grafts. This situation seems close to that seen for liver grafts from anti-HBc positive donors that can be now safely transplanted in recipients receiving antiviral drugs or antiHBs immunoglobulins [8]. Cyrille Fe´ray Institut National de la Sante´ et de la Recherche Me´dicale (INSERM), Unit 481, Faculte´ de Me´decine, Xavier Bichat, 16 rue Huchard, Paris, France E-mail address: [email protected]
0168-8278/$30.00 q 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.jhep.2003.10.001
1104
Beyond the Journal
References [1] Vargas HE, Laskus T, Wang LF, Lee R, Radkowski M, Dodson F, et al. Outcome of liver transplantation in hepatitis C virus-infected patients who received hepatitis C virus-infected grafts. Gastroenterology 1999; 117:149–153. [2] Marroquin CE, Marino G, Kuo PC, Plotkin JS, Rustgi VK, Lu AD, et al. Transplantation of hepatitis C-positive livers in hepatitis C-positive patients is equivalent to transplanting hepatitis C-negative livers. Liver Transpl 2001;7:762–768. [3] Velidedeoglu E, Desai NM, Campos L, Olthoff KM, Shaked A, Nunes F, et al. The outcome of liver grafts procured from hepatitis C-positive donors. Transplantation 2002;73:582– 587. [4] Saab S, Ghobrial RM, Ibrahim AB, Kunder G, Durazo F, Han S, et al. Hepatitis C positive grafts may be used in orthotopic liver
[5]
[6]
[7]
[8]
transplantation: a matched analysis. Am J Transplant 2003;3: 1167–1172. Radkowski M, Wang LF, Vargas H, Wilkinson J, Rakela J, Laskus T. Changes in hepatitis C virus population in serum and peripheral blood mononuclear cells in chronically infected patients receiving liver graft from infected donors. Transplantation 2001;72:833–838. Mehta SH, Cox A, Hoover DR, Wang XH, Mao Q, Ray S, et al. Protection against persistence of hepatitis C. Lancet 2002;359: 1478–1483. Kalinina O, Norder H, Mukomolov S, Magnius LO. A natural intergenotypic recombinant of hepatitis C virus identified in St. Petersburg. J Virol 2002;76:4034–4043. Roque-Afonso AM, Feray C, Samuel D, Simoneau D, Roche B, Emile JF, et al. Antibodies to hepatitis B surface antigen prevent viral reactivation in recipients of liver grafts from anti-HBC positive donors. Gut 2002;50:95–99.
BEYOND THE JOURNAL Associate Editors: Guadalupe Garcia-Tsao and Ronald Oude Elferink Committee: James Boyer, Jean-Franc¸ois Dufour, Hartmut Jaeschke, Luigi Pagliaro, Jorge Rakela, Tania Roskams and Christian Trautwein
HCV infected liver graft
Shortage of grafts is a major limitation of liver transplantation leading to the use of marginal liver grafts. Previous retrospective studies have suggested that antihepatitis C virus (HCV) positive recipients could be given liver grafts harvested in anti-HCV positive donors without detrimental influence on graft function and survival [1 – 4]. One study [1] reported that chronic coinfection by donor’s and recipient’s strain was infrequent. Each strain had the same probability to predominate as shown in the paper of Fan et al. The takeover of one strain seemed to be complete and long lasting [5]. Very interestingly, it was suggested that when donor’s strain predominate, the severity of recurrence was less severe. Fan et al. paper confirmed that the strain from the donor became predominant in around half of the cases. This is very important to consider since the resistance to interferon is not similar among different genotypes. For that reason and for recipients infected with genotypes 2 or 3, donor’s genotype should be ideally determined in order to avoid superinfection by HCV genotype 1. This clinical setting is an unique opportunity to study the coinfection by two different strains of HCV in humans. It is far to be an academic issue since it appears that multiple infections are frequent events in drug users who are highly exposed to repeated infections [6]. Classically, when two strains of a single strand positive RNA viruses compete in an individual, one strain became predominant due to its higher fitness, thus explaining that chronic coinfection is a rather infrequent event during infection by HCV. Predominance of one strain is also the rule in this study as well as in the larger Vargas’ study [1]. The possibility of recombination between strains belonging to different taxonomic genotypes as been reported for HCV [7]. This could be a major limitation of the use of livers harvested in HCV-positive patients due to the potential risk of emergence of a new strain at risk for the community and not only for the recipient. However, this risk seems mostly
theoretical since in important population of IV drug users, multiples challenges are frequent [6]. No recombinant strain has been observed in the paper of Fan et al. Although the number of cases is limited (n ¼ 6), these findings are encouraging, showing that the possibility of emergence of recombinant HCV strain, if any, is probably low. On a practical point of view, what to do? The use of antiHCV positive recipients is forbidden in France for instance while it seems a relatively frequent procedure in USA. Should we propose anti-HCV positive recipients to receive graft from anti-HCV positive recipients? Ideally, informed anti-HCV positive recipients should receive a graft with almost normal histology, which has been harvested in recipient infected with a compatible genotype. This will require, in the emergency setting of liver transplantation, extemporaneous liver histology and rapid determination of recipient’s genotype. Furthermore, those recipients should have a precise virological follow-up in order to detect the possibility of viral recombinants. This follow-up is technically feasible but remains extremely heavy and costly. Retrospective clinical and virological studies seems now sufficient to encourage the use of such livers. Finally, the highly probable development of future active antiviral drugs against HCV should facilitate the use of such marginal liver grafts and help to increase the total pool of liver grafts. This situation seems close to that seen for liver grafts from anti-HBc positive donors that can be now safely transplanted in recipients receiving antiviral drugs or antiHBs immunoglobulins [8]. Cyrille Fe´ray Institut National de la Sante´ et de la Recherche Me´dicale (INSERM), Unit 481, Faculte´ de Me´decine, Xavier Bichat, 16 rue Huchard, Paris, France E-mail address: [email protected]
0168-8278/$30.00 q 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.jhep.2003.10.001
1104
Beyond the Journal
References [1] Vargas HE, Laskus T, Wang LF, Lee R, Radkowski M, Dodson F, et al. Outcome of liver transplantation in hepatitis C virus-infected patients who received hepatitis C virus-infected grafts. Gastroenterology 1999; 117:149–153. [2] Marroquin CE, Marino G, Kuo PC, Plotkin JS, Rustgi VK, Lu AD, et al. Transplantation of hepatitis C-positive livers in hepatitis C-positive patients is equivalent to transplanting hepatitis C-negative livers. Liver Transpl 2001;7:762–768. [3] Velidedeoglu E, Desai NM, Campos L, Olthoff KM, Shaked A, Nunes F, et al. The outcome of liver grafts procured from hepatitis C-positive donors. Transplantation 2002;73:582– 587. [4] Saab S, Ghobrial RM, Ibrahim AB, Kunder G, Durazo F, Han S, et al. Hepatitis C positive grafts may be used in orthotopic liver
[5]
[6]
[7]
[8]
transplantation: a matched analysis. Am J Transplant 2003;3: 1167–1172. Radkowski M, Wang LF, Vargas H, Wilkinson J, Rakela J, Laskus T. Changes in hepatitis C virus population in serum and peripheral blood mononuclear cells in chronically infected patients receiving liver graft from infected donors. Transplantation 2001;72:833–838. Mehta SH, Cox A, Hoover DR, Wang XH, Mao Q, Ray S, et al. Protection against persistence of hepatitis C. Lancet 2002;359: 1478–1483. Kalinina O, Norder H, Mukomolov S, Magnius LO. A natural intergenotypic recombinant of hepatitis C virus identified in St. Petersburg. J Virol 2002;76:4034–4043. Roque-Afonso AM, Feray C, Samuel D, Simoneau D, Roche B, Emile JF, et al. Antibodies to hepatitis B surface antigen prevent viral reactivation in recipients of liver grafts from anti-HBC positive donors. Gut 2002;50:95–99.