Genetic similarity of hepatitis C virus and fibrosis progression in chronic and recurrent infection after liver transplantation

Abstract

The effect of hepatitis C virus (HCV) genetic heterogeneity on clinical features of post-transplantation hepatitis C is controversial. Different regions of the HCV genome have been associated with apoptosis, fibrosis, and other pathways leading to liver damage in chronic HCV infection. Besides, differences in immunodominant regions, such as NS3, may influence HCV-specific immune responses and disease outcome. In the liver transplant setting, a recent study has reported a positive association between HCV-1b Core region genetic relatedness 5-year post-transplantation and histological severity of recurrent hepatitis C. We have compared nucleotide sequences of HCV Core, NS3 and NS5b regions in HCV-1b-infected patients 3 years post-transplantation (n = 22). A cohort of nontransplanted patients (n = 22) was used as control of natural chronic HCV-1b infection. Histological evaluation was used to define the rate of fibrosis progression. Molecular variance analysis did not show significant differences in HCV sequences between transplanted and nontransplanted patients, or between those with fast or slow fibrosis progression. The same results were obtained when analysing phylogenetic trees for Core, NS3 and NS5b regions. A more appropriate clustering method (using minimum spanning networks) revealed a significant positive relationship between HCV genetic similarity in Core (r = 0.550, P < 0.01) and NS5b regions (r = 0.847, P < 0.01) and the yearly rate of fibrosis progression in nontransplanted patients which, in contrast, was not observed in transplanted patients. Our results indicate that some strains of HCV-1b might be more pathogenic in the natural course of chronic infection by this virus subtype. In the liver transplant setting, when the immune response is severely compromised, other mechanisms are probably more important in determining hepatitis C progression.

Hepatitis C virus viral kinetics during α-2a or α-2b pegylated interferon plus ribavirin therapy in liver transplant recipients with different immunosuppression regimes

“…14,43 In some of our LT patients, virus half-life during the first phase decline appears longer than that published for non-immunosuppressed individuals, but consistent with the range observed (1. [13][14][15][16][17][18][19].0) in the only other available study exploring this variable in treated LT-recipients. 16 Collectivelly, these observations suggest differential HCV kinetics with immunosupression.…”

“…18 Viral load was quantified using the HCV Amplicor monitor 2.0 or the Cobas 2.0 methods, both with a limit of detection of 600 IU/mL (Roche). Samples were diluted 1/10, and negative diluted samples were re-tested undiluted.…”

Inter and intra-host variability of hepatitis C virus genotype 1a hypervariable envelope coding domains followed for a 4–11 year of human immunodeficiency virus coinfection and highly active antiretroviral therapy

“…The clinical relevance of the E2 genetic variation is also uncertain, but decreased variability in HCV quasispecies over time has been associated with more advanced liver disease (Chayama and Hayes, 2011;Gretch et al, 1996;Lopez-Labrador et al, 2006). Certain immunosuppressed states are associated with reduced quasispecies heterogeneity (Feliu et al, 2004;Gray et al, 2012;Kumar et al, 1994;Schramm et al, 2008).…”

Computational models of liver fibrosis progression for hepatitis C virus chronic infection

“…Sequences of HCV 1b isolates were identified through a study on cohorts of liver transplanted (TOH; n = 22) and non-transplanted - immunocompetent - patients (IC; n = 22) [18]. In order to conduct an interaction/dependency-based analysis, sequences from these three genomic regions were concatenated into a single nt sequence, aligned and annotated with clinical data.…”