Hepatitis C virus genotypes and the influence of the induction of immunosuppression with anti-thymocyte globulin (ATG) on chronic hepatitis in renal graft recipients

Abstract

Hepatitis C virus (HCV) exhibits a dramatic genetic variability and several mechanisms of immunological response are unable to control hepatic and extrahepatic replication. Genotype 1 b is associated with more severe clinical manifestations and is less responsive to interferon. In addition, we have reported an increase of HCV RNA viral load after renal transplantation. Anti-thymocyte globulin (ATG) is supposed to increase viral replication and liver dysfunction in chronically infected renal graft recipients. We evaluated the genotype profile in HCV+ patients of our Renal Transplant Unit and studied the effects of ATG, as part of the induction of immunosuppression, on viral load and liver enzymes abnormalities. From 726 renal graft recipients, 104 patients, with a mean follow up of 3.9 +/- 2.9 years, were anti-HCV+ by ELISA II. HCV RNA was measured by quantitative PCR. We correlated the viral load and biochemical liver parameters with genotype, exposure to ATG as induction therapy, early acute rejection episode and the duration of infection. Of the 81 patients tested, 72% were viraemic and genotype 1 b was the predominant viral strain (66%). The majority of these patients (65%) were coinfected by two or more strains. There was no correlation between HCV RNA blood levels and liver enzymes. We did not find higher viral load with genotype 1 b infection (68 +/- 88 mEq/ml vs 75.8 +/- 123 mEq/ml in the others) nor with ATG induction therapy (43.5 +/- 71.3 mEq/ml vs 64.1 +/- 110.5 mEq/ml). Early acute rejection and longer follow up were not associated with higher levels of HCV RNA. The biochemical liver profile showed no relationship with the variables studied. We concluded that genotype 1 b is the predominant strain in our HCV+ population and there is a great prevalence of coinfection with several genotypes. Our results did not confirm a deleterious effect of the use of ATG as induction therapy in these HCV-infected patients. Prospective randomised studies with liver biopsy evaluation are needed to answer more fully the remaining questions about the best immunosuppressive therapy in renal graft recipients with chronic HCV infection.

Epidemic history of hepatitis C virus genotypes and subtypes in Portugal

“…We applied phylogenetic and phylodynamic analysis to NS5b sequences obtained from DAA naïve HCV infected patients to make the first characterization of the origin, diversity and epidemiologic history of HCV in Portugal. Like in previous studies, the most prevalent HCV variants were GT1a, representing almost half of the sequences analyzed, followed by GT3a and GT1b 58 – 62 . These genotypes are responsible for the majority of the HCV cases globally 63 , 65 , 66 .…”

“…Based on four previous studies performed between 1998 and 2014, the majority of HCV infections in Portugal are caused by GT1 followed by GT3, GT4 and GT2 58 – 63 . The origin, epidemiological history and transmission dynamics of these genotypes in Portugal have not been investigated.…”

Campath induction in HCV and HCV/HIV-seropositive kidney transplant recipients

“…Another SRTR analysis observed similar patient survival in HCV+ recipients receiving depleting and nondepleting agents . In a retrospective review of 104 HCV‐infected kidney transplant recipients, patients who received induction with antithymocyte globulin had similar HCV viral load on follow‐up as compared to patients without induction . In a recent single‐center study that evaluated long‐term outcomes of 110 HCV‐infected patients after KTX, a subset analysis of 31 recipients showed that patients who received daclizumab had a worse progression of liver fibrosis score than patients receiving a lymphocyte‐depleting agent .…”

“…However, a major risk factor for infectious complications after solid organ transplantation is immunosuppression, including both maintenance therapy and agents used for induction or rejection. Some small studies have shown promising results with antithymocyte globulin or basiliximab in terms of viral infection, cirrhosis, and patient mortality in HCV+ renal transplant recipients . In a SRTR analysis, Luan et al .…”

Hepatitis B and C in Kidney Transplantation

“…It is therefore avoided in HCVinfected patients after transplantation. On the other hand, the administration of the polyclonal antibody antithymocyte globulin (ATG) as induction therapy in 104 HCV-infected kidneytransplant patients did not induce viral replication [106], a finding that was confirmed by subsequent studies [107]. Contradictory data exist regarding monoclonal anti-IL2 antibodies, Advances in Treatment of Hepatitis C and B 236 Please use Adobe Acrobat Reader to read this book chapter for free.…”