Genetic variability and relatedness of hepatitis C virus strains and their effects on liver fibrosis progression

Poster number: 5

F. Xavier López-Labrador (1,2), Alma Bracho (1), Mireia Coscolla (1), Marina Berenguer (3), María D. Gómez (4), Martín Prieto (3), Andrés Moya (1), Fernando González-Candelas (1).

  1. “Cavanilles” Institute for Biodiversity and Evolutionary Biology, University of Valencia, Ap. 22085, 46071 Valencia, Spain
  2. Public Health Department, Generalitat Valenciana
  3. HepatoGastroenterology
  4. Microbiology Services, Hospital Universitari La Fe, Av. Campanar 21, 46009 Valencia, Spain

Computational biology has become one of the main tools for the analysis of viruses and their effects on their hosts, with applications ranging from structural biology to epidemiology and including molecular evolution and drug design, among many others. Although their final goal is to provide new means to fight viral infections, and hence contribute to improve public health, in many cases these applications are not as close as desirable to clinical practice. Here we present an example of such an application where we have looked for factors affecting the different outcomes of a given infection in different patients. More specifically, we have searched for viral genetic features linked to severe outcomes of infection by hepatitis C virus (HCV) and rapidly-progressing liver fibrosis after liver transplantation. Because the liver is the main replication site of HCV, in HCV+ patients reinfection is universal after liver transplantation and soon hepatic fibrosis is established. Why in some patients infected with HCV-1b the progression of liver fibrosis is slow, while in others is fast, leading to cirrhosis and ultimately to liver transplantation or death, is not understood yet. Both host and viral factors may be involved in this differential evolution of chronic infection. We have compared viral isolates from HCV-1b infected patients with slow or fast fibrosis progression from two different populations of HCV-1b chronically-infected patients: 1) liver transplant recipients under immunosupression, and 2) non-transplanted patients. Viral genome sequences from HCV Core, NS3 and NS5b regions were obtained from serum samples and compared by phylogenetic analyses and other genetic computational methods. Although no significant grouping of viral isolates was observed by conventional phylogenetic analysis, using a more appropriate method of genetic analysis minimun spanning networks- a significant association was found between the genetic similarity of HCV in Core (r=0.550, P<0.01) and NS5b (r=0.847, P< 0.01) and the annual fibrosis progression rate in non-transplant patients, but not in transplant patients with recurrent hepatitis C. These results indicate that some particular HCV-1b strains may be associated with fast fibrosis progression in chronic hepatitis C caused by this genotype, but not after liver transplantation, a situation where other mechanisms may influence liver damage to a greater degree than the viral strain. Our study is an example of the potential contributions of molecular epidemiology to translational research in a clinically-relevant problem. Further applications of molecular epidemiology for tracking viral resistance will be also discussed.