Human β‐Herpesvirus Interactions in Solid Organ Transplant Recipients

Mendez, Julio; Dockrell, David H.; Espy, Mark J.; Smith, Thomas F.; Wilson, Jennie; Harmsen, William S.; Ilstrup, Duane M.; Payá, Carlos V.

doi:10.1086/317929

Cited by 179 publications

(163 citation statements)

References 36 publications

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“…The immunomodulatory effects of CMV have been suggested to account for a higher predis position to develop infections due to other opportunistic infections including fungi, other viruses, and bacteria such as Nocardia sp [20,21] . CMVinfected transplant recipients are also more likely to develop EpsteinBarr virus associated posttransplant lymphoproliferative disorders (PTLD), or develop coinfections with other viruses such as the human herpesviruses HHV6 and HHV7 [20,22] . There is a welldescribed interaction between members of the beta herpes group of viruses, known as βherpesvirus syn drome, as exemplified by observations that reacti vations of HHV6 and HHV7 are significantly associated with an increased predisposition to CMV disease after li ver trans plantation [2325] .…”

Section: Indirect CMV Effectsmentioning

confidence: 99%

“…Virusvirus interactions have been proposed to enhan ce the risk of CMV disease after liver transplantati on [22,23,2731] . HHV6 has been associated with an increased predisposition to develop CMV disease after li ver transp lantation [22,23,25] .…”

Section: Virus-to-virus Interactionsmentioning

confidence: 99%

“…HHV6 has been associated with an increased predisposition to develop CMV disease after li ver transp lantation [22,23,25] . Likewise, HCVinfected liver transplant patients have a higher incidence of CMV disease [54] , al though the advent of valganciclovir prophylaxis has all owed mitigation of this phenomenon [26] .…”

Section: Virus-to-virus Interactionsmentioning

confidence: 99%

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Current concepts on cytomegalovirus infection after liver transplantation

Lee

Razonable

2010

WJH

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Cytomegalovirus (CMV) is the most common viral pathogen that negatively impacts on the outcome of liver transplantation. CMV cause febrile illness often accompanied by bone marrow suppression, and in some cases, invades tissues including the transplanted allograft. In addition, CMV has been significantly asso ciated with an increased predisposition to allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall pa tient and allograft survival. To negate the adverse effects of CMV on outcome, its prevention, whether through antiviral prophylaxis or preemptive therapy, is regarded as an essential component to the medical management of liver transplant patients. Two recent guidelines have suggested that antiviral prophylaxis or preemptive therapy are similarly effective in preventing CMV disease in modest-risk CMV-seropositive liver trans plant recipients, while antiviral prophylaxis is the preferred strategy over preemptive therapy for the preven tion of CMV disease in high-risk recipients [CMV-seronegative recipients of liver allografts from CMV-seropositive donors (D+/R-)]. However, antiviral prophylaxis has only delayed the onset of CMV disease in many CMV D+/R-liver transplant recipients, and at least in one study, such occurrence of late-onset primary CMV disease was significantly associated with increased mortality after liver transplantation. Therefore, optimized strategies for prevention are needed, and aggressive treatment of CMV infection and disease should be pursued. The standard treatment of CMV disease consists of intravenous ganciclovir or oral valganciclovir, and if feasible, one should also reduce the degree of immunosuppression. In one recent controlled clinical trial, val ganciclovir was found to be as effective and safe as intravenous ganciclovir for the treatment of mild to mo derate CMV disease in solid organ (including liver) tran splant recipients. In this article, the authors review the current state and the future perspectives of prevention and treatment of CMV disease after liver transplantation.

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Section: Indirect CMV Effectsmentioning

confidence: 99%

Section: Virus-to-virus Interactionsmentioning

confidence: 99%

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Current concepts on cytomegalovirus infection after liver transplantation

Lee

Razonable

2010

WJH

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“…96 In addition, the activation of the other herpesviruses human herpesvirus-6 and Epstein-Barr virus has been reported with CMV. [97][98][99] Cytomegalovirus is also suggested to be involved in liver rejection-including an association with chronic rejection. 100,101 CMV triggers inflammation in the graft by upregulation of cytokines, MHC antigens and adhesion molecules, and induces various chemokines and growth factors.…”

Section: Cytomegalovirusmentioning

confidence: 99%

Infections After Orthotopic Liver Transplantation

Pedersen

Seetharam

2014

Journal of Clinical and Experimental Hepatology

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Opportunistic infections are a leading cause of morbidity and mortality after orthotopic liver transplantation. Systemic immunosuppression renders the liver recipient susceptible to de novo infection with bacteria, viruses and fungi post-transplantation as well to reactivation of pre-existing, latent disease. Pathogens are also transmissible via the donor organ. The time from transplantation and degree of immunosuppression may guide the differential diagnosis of potential infectious agents. However, typical systemic signs and symptoms of infection are often absent or blunted after transplant and a high index of suspicion is needed. Invasive procedures are often required to procure tissue for culture and guide antimicrobial therapy. Antimicrobial prophylaxis reduces the incidence of opportunistic infections and is routinely employed in the care of patients after liver transplant. In this review, we survey common bacterial, fungal, and viral infections after orthotopic liver transplantation and highlight recent developments in their diagnosis and management. ( J CLIN EXP HEPATOL 2014;4:347-360) I nfection after orthotopic liver transplantation (OLT) is a major cause of morbidity and mortality. Infection is estimated to occur in upto 80% of organ recipients. Bacterial infections are most frequent (70%), followed by viral (20%) and fungal infections (8%). 1,2,3 In addition to direct effects of infection and end-organ inflammation, pathogens may have a number of indirect effects that result in allograft injury, rejection and opportunistic superinfection.The risk of infection in liver transplant recipients is determined by the intensity of exposure to infectious agents and the overall level of immunosuppression. 4 In addition, conditions attendant to end-stage liver disease in the immediate perioperative period may render a recipient vulnerable to infection and include: neutropenia, deficits in mucocutaneous barrier integrity, presence of necrotic tissue, ischemia, diabetes mellitus, immunomodulating viruses, uremia, and protein-calorie malnutrition. 5 Infectious exposures come from many sources post liver transplant including: de novo (acquired acute) in the recipient, reactivation in the recipient, the donor organ, and nosocomial and time from transplant may provide clues to etiology (Figure 1). The overall level of immunosuppression is dependent upon the dose, duration, and choice of immunosuppression as well as underlying immune deficiencies. 6 Inflammatory responses to invading pathogens are often blunted by immunosuppressive therapy, and as a result, the classic signs or symptoms of infection may be absent. A high index of suspicion is need in the liver recipient, and a low threshold to perform invasive diagnostic procedures is often required. It is critical to identify clinical factors that predispose recipients to infection and much interest centers on identifying risk factors for infection after liver transplant. GENETIC POLYMORPHISMS IN THE INNATE IMMUNE SYSTEMIn addition to clinical factors that promote ...

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“…Several groups of investigators have now identified a potential interaction between the development of HHV6 and HHV7 and CMV infection in organ transplant recipients. 60,61 Reactivation of HHV6 infection following LTx has been associated with the development of an increased CMV viral load and a greater likelihood of developing CMV disease. 61 It has also been suggested that some or all of the symptoms typically associated with CMV syndrome in patients with proven CMV infection may be attributable in part to HHV6 or HHV7.…”

Section: Other Herpesvirusesmentioning

confidence: 99%