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.
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ABSTRACT: The persistence of chronic immune activation and oxidative stress in human immunodeficiency virus (HIV)-infected, antiretroviral drug-treated individuals are major obstacles to fully preventing HIV disease progression. The immune modulator and antioxidant dimethyl fumarate (DMF) is effective in treating immune-mediated diseases and it also has potential applications to limiting HIV disease progression. Among the relevant effects of DMF and its active metabolite monomethyl fumarate (MMF) are induction of a Th1 to Th2 lymphocyte shift, inhibition of pro-inflammatory cytokine signaling, inhibition of NF-κB nuclear translocation, inhibition of dendritic cell maturation, suppression of lymphocyte and endothelial cell adhesion molecule expression, and induction of the Nrf2-dependent antioxidant response element (ARE) and effector genes. Associated with these effects are reduced lymphocyte and monocyte infiltration into psoriatic skin lesions in humans and immune-mediated demyelinating brain lesions in rodents, which confirms potent systemic and central nervous system (CNS) effects. In addition, DMF and MMF limit HIV infection in macrophages in vitro, albeit by unknown mechanisms. Finally, DMF and MMF also suppress neurotoxin production from HIV-infected macrophages, which drives CNS neurodegeneration. Thus, DMF might protect against systemic and CNS complications in HIV infection through its effective suppression of immune activation, oxidative stress, HIV replication, and macrophage-associated neuronal injury.Critical Reviews in Immunology 01/2013; 33(4):307-59. · 3.89 Impact Factor
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ABSTRACT: Classical HIV-associated nephropathy (HIVAN) was first described before the advent of highly active antiretroviral therapy in late stages of HIV disease with high viral load and low CD4 cell count. Renal transplantation has been successful in a large series of carefully selected HIV-infected adults, with patient and renal allograft survival approaching those of non-HIV-infected patients. We report the successful outcome of living related renal transplantation in a vertically transmitted HIV-infected 8-year-old girl with end-stage kidney disease on haemodialysis due to HIVAN. The pretransplant preparations and post-transplant care, with particular emphasis on immunosuppression and avoidance of opportunistic infections, are discussed.Archives of Disease in Childhood 08/2014; · 2.91 Impact Factor
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ABSTRACT: Before the introduction of combined highly active antiretroviral therapy, a positive human immunodeficiency virus (HIV) serological status represented an absolute contraindication for solid organ transplant (SOT). The advent of highly effective combined antiretroviral therapy in 1996 largely contributed to the increased demand for SOT in HIV-positive individuals due to increased patients' life expectancy associated with the increasing prevalence of end-stage liver disease (ESLD). Nowadays, liver failure represents a frequent cause of mortality in the HIV-infected population mainly due to coinfection with hepatitis viruses sharing the same way of transmission. Thus, liver transplantation (LT) represents a reasonable approach in HIV patients with stable infection and ESLD. Available data presently supports with good evidence the practice of LT in the HIV-positive population. Thus, the issue is no longer "whether it is correct to transplant HIV-infected patients", but "who are the patients who can be safely transplanted" and "when is the best time to perform LT". Indeed, the benefits of LT in HIV-infected patients, especially in terms of mid- and long-term patient and graft survivals, are strictly related to the patients' selection and to the correct timing for transplantation, especially when hepatitis C virus coinfection is present. Aim of this article is to review the pros and cons of LT in the cohort of HIV infected recipients.World Journal of Gastroenterology 05/2014; 20(18):5353-5362. · 2.43 Impact Factor