Abstract
Liver disease is a leading cause of mortality among HIV-infected persons in the highly active anti-retroviral therapy (HAART) era. Hepatitis C Virus (HCV) co-infection is prevalent in, and worsened by HIV; consequently many co-infected persons require liver transplantation (LT). Despite the need, post-LT outcomes are poor in co-infection. We examined predictors of outcomes post-LT. Immunologic biomarkers of immune activation, microbial translocation, and Th1/Th2 skewing were measured pre-LT in participants enrolled in a cohort of HIV infected persons requiring solid organ transplant (HIVTR). Predictive biomarkers were analyzed in Cox-proportional hazards models; multivariate models included known predictors of outcome and biomarkers from univariate analyses. Sixty-nine HIV-HCV co-infected persons with available pre-LT samples were tested: median (IQR) CD4+ T-cell count was 286 (210–429) cells mm-3; 6 (9%) had detectable HIV RNA. Median (IQR) follow-up was 2.1 (0.7–4.0) years, 29 (42%) people died, 35 (51%) had graft loss, 22 (32%) were treated for acute rejection, and 14 (20%) had severe recurrent HCV. In multivariate models, sCD14 levels were significantly lower in persons with graft loss post-LT (HR 0.10 [95%CI 0.02–0.68]). IL-10 levels were higher in persons with rejection (HR 2.10 [95%CI 1.01–4.34]). No markers predicted severe recurrent HCV. Monocyte activation pre-LT may be mechanistically linked to graft health in HIV-HCV co-infection.
Highlights
Liver disease is a leading cause of mortality in HIV despite major advances in treatment with highly active antiretroviral therapy (HAART).[1]
Liver Transplantation Outcomes in HIV-Hepatitis C Virus (HCV). On this point, because the HIV infected persons requiring solid organ transplant (HIVTR) is a registry that accounted for 84% of ALL liver transplants that were performed in the US during the study period in HIV/ HCV co-infected persons, and because the final models were adjusted for a) the presence of kidneyliver transplantation, b) BMI, and c) donor age, the authors believe that there may be sufficient data in an expanded data set to be able to identify individual patients among the 69 HIVTR participants
Immune activation is thought to drive AIDS progression in the non-transplant HIV-infected population[6] and may contribute to liver disease progression; we found that microbial translocation (MT) from intestinal CD4+ T cell depletion was associated with immune activation and was strongly associated with cirrhosis in HIV-HCV co-infected persons.[7]
Summary
Liver disease is a leading cause of mortality in HIV despite major advances in treatment with highly active antiretroviral therapy (HAART).[1]. HIV-infected patients have worse outcomes after liver transplantation than HIV uninfected patients, the underlying mechanisms are PLOS ONE | DOI:10.1371/journal.pone.0135882. Liver Transplantation Outcomes in HIV-HCV on this point, because the HIVTR is a registry that accounted for 84% of ALL liver transplants that were performed in the US during the study period in HIV/ HCV co-infected persons, and because the final models were adjusted for a) the presence of kidneyliver transplantation, b) BMI, and c) donor age, the authors believe that there may be sufficient data in an expanded data set to be able to identify individual patients among the 69 HIVTR participants. Data will be made fully available upon request to the Study PI at UCSF, Dr Peter Stock
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