HCV infection raises risk of death after kidney transplant

SAN FRANCISCO – Infection with hepatitis C virus is a risk factor for poor outcomes after kidney transplantation, but infection with human immunodeficiency virus is not, finds a cohort study reported at the 2014 World Transplant Congress.

"Centers should be more selective in transplanting HCV-positive kidney transplant candidates. But controlled HIV infection should no longer be perceived as a barrier to kidney transplantation," said first author Dr. Deirdre L. Sawinski of the University of Pennsylvania in Philadelphia.

Further, control of hepatitis C with treatment should be a priority in hopes of improving outcomes, she added.

Researchers studied 111,990 patients from the United Network for Organ Sharing (UNOS) database who had a known serostatus and underwent kidney transplantation in 1996 or later when highly active antiretroviral therapy became widespread. Overall, 4.6% were infected with HCV alone, 0.4% were infected with HIV alone, and 0.1% were coinfected.

Multivariate analyses adjusted for a variety of donor and recipient characteristics, and included a variable for transplant after 2001. This time point "reflects both the year in which more than half of patients were discharged on tacrolimus maintenance therapy as well as the year in which interferon therapy was approved for treatment for hepatitis C," Dr. Sawinski said.

HCV-infected patients and especially HCV and HIV-coinfected patients had significantly higher risks of death (hazard ratio, 1.52 and 3.83, respectively) and of graft loss (HR, 1.48 and 3.40, respectively), compared with uninfected patients. In contrast, patients infected with HIV alone were not at higher risk of death or graft loss.

"The main cause of death for the reference [uninfected] group and the hep C–positive patients was listed as cardiovascular disease, whereas the HIV-positive and coinfected patients most often had infection as their causes of death," Dr. Sawinski said. "However, you have to take that with a grain of salt as 40% of patients across all four groups had missing data [regarding] cause of death."

The risk persisted even after researchers corrected for the impact of antibody-depleting therapy during transplantation on graft survival. However, the UNOS database does not provide information about treatment with interferon before and after direct-acting antiretroviral drugs became available. Additionally, Dr. Sawinski noted, "the UNOS data set does not identify which patients are actually viremic vs. antibody positive." Data are similarly nonspecific for deceased donors but are detailed (antibody positive vs. viremic) for living donors.

A secondary analysis considered a cohort of 180,177 patients with unknown serostatus. In this analysis, the risks of death and graft loss were elevated among patients with dual unknown status relative to those known to be dually uninfected (HR, 1.06 and 1.02), according to data reported at the 2014 World Transplant Congress, which was sponsored by the American Society of Transplant Surgeons. However, these small elevations of risk are "probably not clinically meaningful," commented Dr. Sawinski, who disclosed no relevant conflicts of interest. Risks were not significantly elevated for HCV-positive patients vs. HCV-positive, HIV-unknown patients, or for HIV-positive patients vs. HIV-positive, HCV-unknown patients.

Additionally, main study findings were essentially the same when the cohort with known serostatus and the cohort with an unknown serostatus were combined and the researchers assumed the unknown status patients were uninfected.

SAN FRANCISCO – Infection with hepatitis C virus is a risk factor for poor outcomes after kidney transplantation, but infection with human immunodeficiency virus is not, finds a cohort study reported at the 2014 World Transplant Congress.

"Centers should be more selective in transplanting HCV-positive kidney transplant candidates. But controlled HIV infection should no longer be perceived as a barrier to kidney transplantation," said first author Dr. Deirdre L. Sawinski of the University of Pennsylvania in Philadelphia.

Further, control of hepatitis C with treatment should be a priority in hopes of improving outcomes, she added.

Researchers studied 111,990 patients from the United Network for Organ Sharing (UNOS) database who had a known serostatus and underwent kidney transplantation in 1996 or later when highly active antiretroviral therapy became widespread. Overall, 4.6% were infected with HCV alone, 0.4% were infected with HIV alone, and 0.1% were coinfected.

Multivariate analyses adjusted for a variety of donor and recipient characteristics, and included a variable for transplant after 2001. This time point "reflects both the year in which more than half of patients were discharged on tacrolimus maintenance therapy as well as the year in which interferon therapy was approved for treatment for hepatitis C," Dr. Sawinski said.

HCV-infected patients and especially HCV and HIV-coinfected patients had significantly higher risks of death (hazard ratio, 1.52 and 3.83, respectively) and of graft loss (HR, 1.48 and 3.40, respectively), compared with uninfected patients. In contrast, patients infected with HIV alone were not at higher risk of death or graft loss.

"The main cause of death for the reference [uninfected] group and the hep C–positive patients was listed as cardiovascular disease, whereas the HIV-positive and coinfected patients most often had infection as their causes of death," Dr. Sawinski said. "However, you have to take that with a grain of salt as 40% of patients across all four groups had missing data [regarding] cause of death."

The risk persisted even after researchers corrected for the impact of antibody-depleting therapy during transplantation on graft survival. However, the UNOS database does not provide information about treatment with interferon before and after direct-acting antiretroviral drugs became available. Additionally, Dr. Sawinski noted, "the UNOS data set does not identify which patients are actually viremic vs. antibody positive." Data are similarly nonspecific for deceased donors but are detailed (antibody positive vs. viremic) for living donors.

A secondary analysis considered a cohort of 180,177 patients with unknown serostatus. In this analysis, the risks of death and graft loss were elevated among patients with dual unknown status relative to those known to be dually uninfected (HR, 1.06 and 1.02), according to data reported at the 2014 World Transplant Congress, which was sponsored by the American Society of Transplant Surgeons. However, these small elevations of risk are "probably not clinically meaningful," commented Dr. Sawinski, who disclosed no relevant conflicts of interest. Risks were not significantly elevated for HCV-positive patients vs. HCV-positive, HIV-unknown patients, or for HIV-positive patients vs. HIV-positive, HCV-unknown patients.

Additionally, main study findings were essentially the same when the cohort with known serostatus and the cohort with an unknown serostatus were combined and the researchers assumed the unknown status patients were uninfected.

SAN FRANCISCO – Infection with hepatitis C virus is a risk factor for poor outcomes after kidney transplantation, but infection with human immunodeficiency virus is not, finds a cohort study reported at the 2014 World Transplant Congress.

"Centers should be more selective in transplanting HCV-positive kidney transplant candidates. But controlled HIV infection should no longer be perceived as a barrier to kidney transplantation," said first author Dr. Deirdre L. Sawinski of the University of Pennsylvania in Philadelphia.

Further, control of hepatitis C with treatment should be a priority in hopes of improving outcomes, she added.

Researchers studied 111,990 patients from the United Network for Organ Sharing (UNOS) database who had a known serostatus and underwent kidney transplantation in 1996 or later when highly active antiretroviral therapy became widespread. Overall, 4.6% were infected with HCV alone, 0.4% were infected with HIV alone, and 0.1% were coinfected.

Multivariate analyses adjusted for a variety of donor and recipient characteristics, and included a variable for transplant after 2001. This time point "reflects both the year in which more than half of patients were discharged on tacrolimus maintenance therapy as well as the year in which interferon therapy was approved for treatment for hepatitis C," Dr. Sawinski said.

HCV-infected patients and especially HCV and HIV-coinfected patients had significantly higher risks of death (hazard ratio, 1.52 and 3.83, respectively) and of graft loss (HR, 1.48 and 3.40, respectively), compared with uninfected patients. In contrast, patients infected with HIV alone were not at higher risk of death or graft loss.

"The main cause of death for the reference [uninfected] group and the hep C–positive patients was listed as cardiovascular disease, whereas the HIV-positive and coinfected patients most often had infection as their causes of death," Dr. Sawinski said. "However, you have to take that with a grain of salt as 40% of patients across all four groups had missing data [regarding] cause of death."

The risk persisted even after researchers corrected for the impact of antibody-depleting therapy during transplantation on graft survival. However, the UNOS database does not provide information about treatment with interferon before and after direct-acting antiretroviral drugs became available. Additionally, Dr. Sawinski noted, "the UNOS data set does not identify which patients are actually viremic vs. antibody positive." Data are similarly nonspecific for deceased donors but are detailed (antibody positive vs. viremic) for living donors.

A secondary analysis considered a cohort of 180,177 patients with unknown serostatus. In this analysis, the risks of death and graft loss were elevated among patients with dual unknown status relative to those known to be dually uninfected (HR, 1.06 and 1.02), according to data reported at the 2014 World Transplant Congress, which was sponsored by the American Society of Transplant Surgeons. However, these small elevations of risk are "probably not clinically meaningful," commented Dr. Sawinski, who disclosed no relevant conflicts of interest. Risks were not significantly elevated for HCV-positive patients vs. HCV-positive, HIV-unknown patients, or for HIV-positive patients vs. HIV-positive, HCV-unknown patients.

Additionally, main study findings were essentially the same when the cohort with known serostatus and the cohort with an unknown serostatus were combined and the researchers assumed the unknown status patients were uninfected.