OKT3 Treatment for Allograft Rejection Is a Risk Factor for Cytomegalovirus Disease in Liver Transplantation

Portela, Daniel; Patel, Robin; Larson-Keller, Jeffrey J.; Ilstrup, Duane M.; Wiesner, Russell H.; Steers, Jeffery L.; Krom, Ruud A.F.; Payá, Carlos V.

doi:10.1093/infdis/171.4.1014

Cited by 133 publications

(83 citation statements)

References 7 publications

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“…CMV infection was defined as the isolation of CMV from any body fluid or tissue, the detection of CMV in tissue, and/or the detection of IgM against CMV in serum. 17 Prospective surveillance for CMV viremia was performed routinely by tube cell and rapid shell vial techniques at weekly intervals for the first 8 weeks after transplantation and thereafter at 3, 6 , and 12 months after transplantation. CMV infection was deemed asymptomatic when CMV infection occurred without clinical symptoms and signs or laboratory abnormalities.…”

Section: Methodsmentioning

confidence: 99%

Development of monoclonal gammopathy precedes the development of Epstein-Barr virus-induced posttransplant lymphoproliferative disorder

et al. 1996

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Epstein-Barr virus (EBV)-induced posttransplant lymphoproliferative disorder (PTLD) develops in 3% to 10% of solid organ transplant recipients with a resultant mortality of up to 70%. Unfortunately, there is no current marker which identifies patients who will develop this disease. We therefore conducted a risk factor analysis of variables that might predict the development of PTLD. Specifically, since EBV may cause both PTLD and the development of monoclonal proteins (M protein), we sought to determine if the development of an M protein preceded and therefore might serve as a predictive marker of subsequent PTLD. Before and after liver transplantation, 201 patients were evaluated for the presence of urine and serum M proteins. Patients were followed to monitor the development of PTLD for a mean of 1,733 days. PTLD developed in seven patients (3.5%), three (43%) of whom died from disseminated PTLD. PTLD was classified as polymorphous in six patients and monomorphous in one patient. Fiftyseven patients (28%) developed an M protein after osttransplant lymphoproliferative disorder P (PTLD) is a serious, potentially life-threatening syndrome that occurs in 3% to 10% of solid organ transplant recipients, depending upon the type of organ transplanted. A causal role for Epstein-Barr virus (EBV) has been invoked, because pathological specimens from patients with PTLD show evidence of EBV gene expression.2 EBV is specifically tropic to epithelial and B cells through the CD21 r e~e p t o r .~ Following infection of epithelial cells, the lytic phase of infection is characterized by massive viral replication and shedding. Thereafter, EBV becomes latent in B cells and may lead to cell transformation. In contrast to uninfected, resting B cells, EBV-transformed B lymphocytes produce and secrete immunoglobulin, notably of the IgM class, as well as immunoglobulin A (IgA) and immunoglobulin G (IgG).4Whereas the normal host's cytotoxic T cell response against infected B cells results in their eradication, the immunosuppressed host is unable to effectively transplantation: five of seven patients (71 %) with PTLD and 52/194 (27%) of patients without PTLD. Multivariate risk factor analysis for the development of an M protein after transplantation identified cytomegalovirus (CMV) donor seropositivity (P = 0.0002) and postoperative symptomatic CMV infection (P = 0.019) as risk factors. Whereas EBV serostatus of either the donor or recipient was not found to be a risk factor for the occurrence of either an M protein or PTLD, the development of a serum immunoglobulin M (IgM) M protein (P = 0.04) and of any urine M protein (P = 0.01) was identified by univariate analysis as being associated with the development of PTLD. Further studies are needed to determine the predictive value of M proteins as a marker for PTLD.

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Section: Methodsmentioning

confidence: 99%

Development of monoclonal gammopathy precedes the development of Epstein-Barr virus-induced posttransplant lymphoproliferative disorder

et al. 1996

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“…The severity of im [5] . mune dysfunction is particularly intense with the use of lymphocytedepleting drugs, as either induction or re jection therapy, such as muromonabCD3 (OKT3) and antithymocyte globulin [37,38] . When alemtuzumab, an antiCD52 lymphocytic antibody, is used for shortcour se induction therapy only, the risk of developing CMV disease is low [39,40] .…”

Section: Drug-induced Immunodeficiencymentioning

confidence: 99%

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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“…Likewise, acute fulminant hepatitis, an additional independent risk factor for CMV disease after OLT, is associated with significant release of inflammatory cytokines. 21 Lastly, such situations as stress secondary to prolonged intra-abdominal surgery or bacterial infections, which are associated with increased levels of lipopolysaccharides, could explain their epidemiological association with an increased risk for CMV disease [22][23][24][25][26][27] (Table 1).…”

Section: Pathogenesismentioning

confidence: 99%