Iron overload and unique susceptibility of liver transplant recipients to disseminated disease due to opportunistic pathogens

Zygomycosis in Solid Organ Transplant Recipients: A Prospective, Matched Case‐Control Study to Assess Risks for Disease and Outcome

“…Previous studies have shown that liver transplant recipients with iron overload are predisposed to early onset opportunistic infections, including invasive fungal infection [21,25]. Although iron overload is potentially amenable to reversal on liver transplantation [20], this may not happen immediately, as evidenced by our data showing development of zygomycosis early after transplantation in liver transplant recipients. Calcineurin inhibitors remain the mainstay of immunosuppression in SOT recipients.…”

“…This propensity could not be explained by known risk factors for invasive fungal infection (tables 3 and 4) and may be related to unique host defense defects or iron overload in liver transplant recipients [20,21]. Iron is not only a pivotal growth factor but also compromises critical host defenses against zygomycetes, including suppression of interferon-g mediated macrophage and monocyte function, reduction of nitrous oxide in macrophages, and impairment of phagocytic activity [20,[22][23][24].…”

“…Iron is not only a pivotal growth factor but also compromises critical host defenses against zygomycetes, including suppression of interferon-g mediated macrophage and monocyte function, reduction of nitrous oxide in macrophages, and impairment of phagocytic activity [20,[22][23][24]. Iron also decreases the proliferation of T cells and alters T helper response towards Th2 predominance that facilitates disease progression [20]. Previous studies have shown that liver transplant recipients with iron overload are predisposed to early onset opportunistic infections, including invasive fungal infection [21,25].…”

Approach to Intraoperative Consultation for Donor Liver Biopsies

“…44 Additionally, nonhemochromatosis transplant recipients have increased iron due to transfusion and to nonfunction of their native liver, and that may predispose those patients to certain opportunistic infections. 45 In our center, donor livers with hepatocyte siderosis up to 2þ/4 are accepted for transplantation.…”

Pathogenesis and clinical consequences of iron overload in chronic hepatitis C -- impact of host and viral factors related to iron metabolism

“…HCV-associated end-stage liver disease is one of the main reasons for liver transplantation in the United States and Europe. Liver transplant recipients who also suffer from iron overload are more susceptible to other diseases like serious fungal, bacterial and viral infections (aspergillosis, cryptococcosis, cytomegaly, infections with Staphylococcus aureus, Yersinia species), relapse of hepatocellular carcinoma and nonhepatic cancers, which significantly decrease the post-transplantation survival rate (Kowdley et al, 2005;Alexander et al, 2006;Singh et al, 2008;Dar et al, 2009). Moreover, hemochromatosis phenotypes as a post-transplantation complication were also observed in HFE-wild-type recipients of livers from donors with HFE mutations (Wigg et al, 2003;Ismail et al, 2009).…”