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Malignancy in the HIV-infected patients undergoing liver and kidney transplantation.

ABSTRACT: The transplant community has seen the gradual acceptance of liver and kidney transplantation in carefully selected HIV-positive patients. The addition of transplant immunosuppressants to an already immunocompromised state, however, may increase the risk of malignancy.Kidney transplantation and liver transplantation have been successful in large series of carefully selected HIV-infected patients, with graft and patient survival approaching those of non-HIV-infected patients. The incidence of acute cellular rejection (kidney transplantation) and of recurrent hepatitis C (liver transplantation) remains challenging. Hepatocellular carcinoma (HCC), which is a common indication for liver transplantation, seems to occur at a younger age and to have a generally worse outcome in the HIV-positive patients. Liver transplantation outcomes for HCC in these patients, however, do not seem to be compromised. Rates of Kaposi's sarcoma and other de-novo malignancies such as skin cancer are relatively low after transplant. Kaposi's sarcoma may regress with the use of the mammalian target of rapamycin inhibitor sirolimus. In HIV-positive patients followed closely for human papilloma virus (HPV)-related anal neoplasia after transplantation, there may be an increased risk of progression to high-grade squamous intraepithelial lesions.The risk of recurrent or de-novo malignancy after solid-organ transplantation in HIV patients is low. HPV-related neoplasia, however, requires further study.

SUBMITTER: Nissen NN

PROVIDER: S-EPMC4283559 | biostudies-other | 2012 Sep

REPOSITORIES: biostudies-other

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Malignancy in the HIV-infected patients undergoing liver and kidney transplantation.

Nissen Nicholas N NN Barin Burc B Stock Peter G PG

Current opinion in oncology 20120901 5

<h4>Purpose of review</h4>The transplant community has seen the gradual acceptance of liver and kidney transplantation in carefully selected HIV-positive patients. The addition of transplant immunosuppressants to an already immunocompromised state, however, may increase the risk of malignancy.<h4>Recent findings</h4>Kidney transplantation and liver transplantation have been successful in large series of carefully selected HIV-infected patients, with graft and patient survival approaching those o ...[more]

PMID: 22759736

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Project description:The outcomes of kidney transplantation and immunosuppression in people infected with human immunodeficiency virus (HIV) are incompletely understood.We undertook a prospective, nonrandomized trial of kidney transplantation in HIV-infected candidates who had CD4+ T-cell counts of at least 200 per cubic millimeter and undetectable plasma HIV type 1 (HIV-1) RNA levels while being treated with a stable antiretroviral regimen. Post-transplantation management was provided in accordance with study protocols that defined prophylaxis against opportunistic infection, indications for biopsy, and acceptable approaches to immunosuppression, management of rejection, and antiretroviral therapy.Between November 2003 and June 2009, a total of 150 patients underwent kidney transplantation; survivors were followed for a median period of 1.7 years. Patient survival rates (±SD) at 1 year and 3 years were 94.6±2.0% and 88.2±3.8%, respectively, and the corresponding mean graft-survival rates were 90.4% and 73.7%. In general, these rates fall somewhere between those reported in the national database for older kidney-transplant recipients (?65 years) and those reported for all kidney-transplant recipients. A multivariate proportional-hazards analysis showed that the risk of graft loss was increased among patients treated for rejection (hazard ratio, 2.8; 95% confidence interval [CI], 1.2 to 6.6; P=0.02) and those receiving antithymocyte globulin induction therapy (hazard ratio, 2.5; 95% CI, 1.1 to 5.6; P=0.03); living-donor transplants were protective (hazard ratio, 0.2; 95% CI, 0.04 to 0.8; P=0.02). A higher-than-expected rejection rate was observed, with 1-year and 3-year estimates of 31% (95% CI, 24 to 40) and 41% (95% CI, 32 to 52), respectively. HIV infection remained well controlled, with stable CD4+ T-cell counts and few HIV-associated complications.In this cohort of carefully selected HIV-infected patients, both patient- and graft-survival rates were high at 1 and 3 years, with no increases in complications associated with HIV infection. The unexpectedly high rejection rates are of serious concern and indicate the need for better immunotherapy. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00074386.).

Project description:Clinical monitoring of cerebral blood flow (CBF) autoregulation in patients undergoing liver transplantation may provide a means for optimizing blood pressure to reduce the risk of brain injury. The purpose of this pilot project is to test the feasibility of autoregulation monitoring with transcranial Doppler (TCD) and near-infrared spectroscopy (NIRS) in patients undergoing liver transplantation and to assess changes that may occur perioperatively.We performed a prospective observational study in 9 consecutive patients undergoing orthotopic liver transplantation. Patients were monitored with TCD and NIRS. A continuous Pearson's correlation coefficient was calculated between mean arterial pressure (MAP) and CBF velocity and between MAP and NIRS data, rendering the variables mean velocity index (Mx) and cerebral oximetry index (COx), respectively. Both Mx and COx were averaged and compared during the dissection phase, anhepatic phase, first 30 min of reperfusion, and remaining reperfusion phase. Impaired autoregulation was defined as Mx ? 0.4.Autoregulation was impaired in one patient during all phases of surgery, in two patients during the anhepatic phase, and in one patient during reperfusion. Impaired autoregulation was associated with a MELD score >15 (p = 0.015) and postoperative seizures or stroke (p < 0.0001). Analysis of Mx categorized in 5 mmHg bins revealed that MAP at the lower limit of autoregulation (MAP when Mx increased to ? 0.4) ranged between 40 and 85 mmHg. Average Mx and average COx were significantly correlated (p = 0.0029). The relationship between COx and Mx remained when only patients with bilirubin >1.2 mg/dL were evaluated (p = 0.0419). There was no correlation between COx and baseline bilirubin (p = 0.2562) but MELD score and COx were correlated (p = 0.0458). Average COx was higher for patients with a MELD score >15 (p = 0.073) and for patients with a neurologic complication than for patients without neurologic complications (p = 0.0245).These results suggest that autoregulation is impaired in patients undergoing liver transplantation, even in the absence of acute, fulminant liver failure. Identification of patients at risk for neurologic complications after surgery may allow for prompt neuroprotective interventions, including directed pressure management.

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Malignancy in the HIV-infected patients undergoing liver and kidney transplantation.

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Malignancy in the HIV-infected patients undergoing liver and kidney transplantation.

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