Heart transplantation (HTX) is the gold standard surgical treatment for patients with advanced heart failure. The prevalence of hepatitis B and hepatitis C infection in HTX recipients is over 10%. Despite its increased prevalence, the long-term outcome in this cohort is still not clear. There is a reluctance to place these patients on transplant waiting list given the increased incidence of viral reactivation and chronic liver disease after transplant. The emergence of new antiviral therapies to treat this cohort seems promising but their long-term outcome is yet to be established. The aim of this paper is to review the literature and explore whether it is justifiable to list advanced heart failure patients with coexistent hepatitis B/C infection for HTX. 1. Introduction Heart transplantation (HTX) is the gold standard surgical treatment for patients with advanced heart failure. Worldwide, the median survival in patients who survive the first year after HTX is about 14 years [1]. This has been attributed to advances in immunosuppressive therapy over the years and importantly, the proper selection of patients who will benefit most from this treatment. Patients undergo extensive investigations from routine biochemistry and virology screening to invasive investigations like right heart catheterisation before being considered for heart transplantation. Patients with significant abnormalities from the assessment are deferred treatment. Though previous infection with Cytomegalovirus and Epstein-Barr virus is not an absolute contraindication, reactivation of these viruses after transplant due to immunosuppression can adversely affect long-term outcome [2, 3]. Hepatotropic viruses (especially hepatitis B and hepatitis C) affect a large number of people throughout the world and they are one of the commonest causes for chronic liver disease and hepatocellular carcinoma [4]. Worldwide, it is estimated that 2 billion people have been infected with hepatitis B and 150 million with hepatitis C. Around 600,000 and 250,000 individuals die each year of complications associated with hepatitis B and hepatitis C infections, respectively. The prevalence of hepatitis B and hepatitis C infection in HTX population is over 10% [5]. Despite its increased prevalence, the long-term outcome in this particular cohort is still not clear. There is no clear consensus as to whether patients with coexistent hepatitis B or C infection, including individuals with a past history of acute resolved infection, should be considered for HTX. The aim of this paper is to review the literature and
References
[1]
J. Stehlik, L. B. Edwards, A. Y. Kucheryavaya et al., “The registry of the international society for heart and lung transplantation: twenty-eighth adult heart transplant report—2011,” Journal of Heart and Lung Transplantation, vol. 30, no. 10, pp. 1078–1094, 2011.
[2]
P. Petrakopoulou, M. Kübrich, S. Pehlivanli et al., “Cytomegalovirus infection in heart transplant recipients is associated with impaired endothelial function,” Circulation, vol. 110, no. 11, supplement 1, pp. II207–II212, 2004.
[3]
K. J. Lewin, “Post-transplant lymphoproliferative disorders,” Pathology and Oncology Research, vol. 3, no. 3, pp. 177–182, 1997.
[4]
C. L. Tinkle and D. Haas-Kogan, “Hepatocellular carcinoma: natural history, current management, and emerging tools,” Biologics, vol. 6, pp. 207–219, 2012.
[5]
F. Lunel, C. Robert, P. Munier et al., “Hepatitis virus infections in heart transplant recipients,” Biomedicine and Pharmacotherapy, vol. 49, no. 3, pp. 125–129, 1995.
[6]
H. A. Valantine, “Cardiac allograft vasculopathy: central role of endothelial injury leading to transplant ‘atheroma’,” Transplantation, vol. 76, no. 6, pp. 891–899, 2003.
[7]
C. Dong, D. Redenbach, S. Wood, B. Battistini, J. E. Wilson, and B. M. McManus, “The pathogenesis of cardiac allograft vasculopathy,” Current Opinion in Cardiology, vol. 11, no. 2, pp. 183–190, 1996.
[8]
S. A. Haji, R. C. Starling, R. K. Avery et al., “Donor hepatitis-C seropositivity is an independent risk factor for the development of accelerated coronary vasculopathy and predicts outcome after cardiac transplantation,” Journal of Heart and Lung Transplantation, vol. 23, no. 3, pp. 277–283, 2004.
[9]
H. A. Valantine, “The role of viruses in cardiac allograft vasculopathy,” The American Journal of Transplantation, vol. 4, no. 2, pp. 169–177, 2004.
[10]
S. A. Haji, R. K. Avery, M. H. Yamani et al., “Donor or recipient hepatitis B seropositivity is associated with allograft vasculopathy,” Journal of Heart and Lung Transplantation, vol. 25, no. 3, pp. 294–297, 2006.
[11]
I. Lee, R. Localio, C. M. Brensinger et al., “Decreased post-transplant survival among heart transplant recipients with pre-transplant hepatitis C virus positivity,” Journal of Heart and Lung Transplantation, vol. 30, no. 11, pp. 1266–1274, 2011.
[12]
S. Fagiuoli, F. Minniti, S. Pevere et al., “HBV and HCV infections in heart transplant recipients,” Journal of Heart and Lung Transplantation, vol. 20, no. 7, pp. 718–724, 2001.
[13]
J. D. Hosenpud, S. R. Pamidi, B. S. Fiol, M. P. Cinquegrani, and B. M. Keck, “Outcomes in patients who are hepatitis B surface antigen-positive before transplantation: an analysis and study using the joint ISHLT/UNOS thoracic registry,” The Journal of Heart and Lung Transplantation, vol. 19, no. 8, pp. 781–785, 2000.
[14]
B. Roche and D. Samuel, “The difficulties of managing severe hepatitis B virus reactivation,” Liver International, vol. 31, supplement 1, pp. 104–110, 2011.
[15]
D. Roth, J. J. Gaynor, K. R. Reddy et al., “Effect of kidney transplantation on outcomes among patients with hepatitis C,” Journal of the American Society of Nephrology, vol. 22, no. 6, pp. 1152–1160, 2011.
[16]
G. A. Knoll, M. R. Tankersley, J. Y. Lee, B. A. Julian, and J. J. Curtis, “The impact of renal transplantation on survival in hepatitis C-positive end-stage renal disease patients,” The American Journal of Kidney Diseases, vol. 29, no. 4, pp. 608–614, 1997.
[17]
F. Fabrizi, P. Martin, V. Dixit, F. Kanwal, and G. Dulai, “HBsAg seropositive status and survival after renal transplantation: meta-analysis of observational studies,” The American Journal of Transplantation, vol. 5, no. 12, pp. 2913–2921, 2005.
[18]
P. N. Reddy, M. S. Sampaio, H. T. Kuo, P. Martin, and S. Bunnapradist, “Impact of pre-existing hepatitis B infection on the outcomes of kidney transplant recipients in the united states,” Clinical Journal of the American Society of Nephrology, vol. 6, no. 6, pp. 1481–1487, 2011.
[19]
H. Sahi, N. N. Zein, A. C. Mehta, H. C. Blazey, K. H. Meyer, and M. Budev, “Outcomes after lung transplantation in patients with chronic hepatitis C virus infection,” Journal of Heart and Lung Transplantation, vol. 26, no. 5, pp. 466–471, 2007.
[20]
M. G. Hartwig, V. Patel, S. M. Palmer et al., “Hepatitis B core antibody positive donors as a safe and effective therapeutic option to increase available organs for lung transplantation,” Transplantation, vol. 80, no. 3, pp. 320–325, 2005.
[21]
G. S. Dhillon, J. Levitt, H. Mallidi et al., “Impact of hepatitis B core antibody positive donors in lung and heart-lung transplantation: an analysis of the United network for organ sharing database,” Transplantation, vol. 88, no. 6, pp. 842–846, 2009.
[22]
A. K. Singal, P. Guturu, B. Hmoud, Y. F. Kuo, H. Salameh, and R. H. Wiesner, “Evolving frequency and outcomes of liver transplantation based on etiology of liver disease,” Transplantation, vol. 95, no. 5, pp. 755–760, 2013.
[23]
K. R. Reddy and G. T. Everson, “Treatment of chronic hepatitis C with protease inhibitor-based therapy after liver transplantation,” Hepatology, vol. 58, no. 3, pp. 1181–1184, 2013.
[24]
H. Akiyama, H. Yoshinaga, T. Tanaka et al., “Effects of cyclosporin A on hepatitis C virus infection in bone marrow transplant patients,” Bone Marrow Transplantation, vol. 20, no. 11, pp. 993–995, 1997.
[25]
K. Inoue, K. Sekiyama, M. Yamada, T. Watanabe, H. Yasuda, and M. Yoshiba, “Combined interferon α2b and cyclosporin A in the treatment of chronic hepatitis C: controlled trial,” Journal of Gastroenterology, vol. 38, no. 6, pp. 567–572, 2003.
[26]
K. Watashi, M. Hijikata, M. Hosaka, M. Yamaji, and K. Shimotohno, “Cyclosporin A suppresses replication of hepatitis C virus genome in cultured hepatocytes,” Hepatology, vol. 38, no. 5, pp. 1282–1288, 2003.
[27]
K. Inoue and M. Yoshiba, “Interferon combined with cyclosporine treatment as an effective countermeasure against hepatitis C virus recurrence in liver transplant patients with end-stage hepatitis C virus related disease,” Transplantation Proceedings, vol. 37, no. 2, pp. 1233–1234, 2005.
[28]
M. M. Hossain, J. J. Coull, G. L. Drusano, and D. M. Margolis, “Dose proportional inhibition of HIV-1 replication by mycophenolic acid and synergistic inhibition in combination with abacavir, didanosine, and tenofovir,” Antiviral Research, vol. 55, no. 1, pp. 41–52, 2002.
[29]
L. Ye, J. Li, T. Zhang et al., “Mycophenolate mofetil inhibits hepatitis C virus replication in human hepatic cells,” Virus Research, vol. 168, no. 1-2, pp. 33–40, 2012.
[30]
Z. J. Gong, S. de Meyer, C. Clarysse et al., “Mycophenolic acid, an immunosuppressive agent, inhibits HBV replication in vitro,” Journal of Viral Hepatitis, vol. 6, no. 3, pp. 229–236, 1999.
[31]
K. C. Lam, C. L. Lai, C. Trepo, and P. C. Wu, “Deleterious effect of prednisolone in HBsAg-positive chronic active hepatitis,” The New England Journal of Medicine, vol. 304, no. 7, pp. 380–386, 1981.
[32]
J. H. Bae, J. H. Sohn, H. S. Lee et al., “A fatal case of hepatitis B virus (HBV) reactivation during long-term, very-low-dose steroid treatment in an inactive HBV carrier,” Clinical and Molecular Hepatology, vol. 18, no. 2, pp. 225–228, 2012.
[33]
Y. J. Kim, S. C. Bae, Y. K. Sung et al., “Possible reactivation of potential hepatitis B virus occult infection by tumor necrosis factor-α blocker in the treatment of rheumatic diseases,” Journal of Rheumatology, vol. 37, no. 2, pp. 346–350, 2010.
[34]
F. Degos, C. Lugassy, C. Degott et al., “Hepatitis B virus and hepatitis B-related viral infection in renal transplant recipients. A prospective study of 90 patients,” Gastroenterology, vol. 94, no. 1, pp. 151–156, 1988.
[35]
S. Fagiuoli, S. Pevere, F. Minniti et al., “Natural leukocyte interferon alfa for the treatment of chronic viral hepatitis in heart transplant recipients,” Transplantation, vol. 75, no. 7, pp. 982–986, 2003.
[36]
B. Y. Wang, H. H. Chang, I. M. Chen, C. C. Shih, and A. H. Yang, “Peginterferon α-2b and acute allograft failure in a heart transplant recipient,” The Annals of Thoracic Surgery, vol. 89, no. 5, pp. 1645–1647, 2010.
[37]
S. S. Wang, N. K. Chou, N. H. Chi et al., “Successful treatment of hepatitis B virus infection with lamivudine after heart transplantation,” Transplantation Proceedings, vol. 38, no. 7, pp. 2138–2140, 2006.
[38]
A. Potthoff, H. L. Tillmann, C. Bara et al., “Improved outcome of chronic hepatitis B after heart transplantation by long-term antiviral therapy,” Journal of Viral Hepatitis, vol. 13, no. 11, pp. 734–741, 2006.
[39]
R. K. Sterling, A. J. Sanyal, V. A. Luketic et al., “Chronic hepatitis C infection in patients with end stage renal disease: characterization of liver histology and viral load in patients awaiting renal transplantation,” The American Journal of Gastroenterology, vol. 94, no. 12, pp. 3576–3582, 1999.
[40]
M. Chandra, M. N. Khaja, M. M. Hussain et al., “Prevalence of hepatitis B and hepatitis C viral infections in Indian patients with chronic renal failure,” Intervirology, vol. 47, no. 6, pp. 374–376, 2004.
