Research

Area 3

Viral hepatitis in the immune competent host and in liver transplant patients

Team leader

Strategic objectives

  • Genetic evolution of hepatitis C virus in the liver transplant setting using ultradeep pyrosequencing.
  • Characterization of hepatitis C virus life cycle using in vitro cell culture models.
  • Development of diagnostic tools for the detection of hepatitis C antigens in liver tissue.
  • Evaluation of new hepatitis C treatments and impact of antiviral treatment in the natural history of chronic hepatitis C.
  • Study of host factors in relation to the natural history and treatment response among patients with chronic hepatitis C.
  • Evaluation of early histological markers of fibrosis progression in liver transplant recipients with hepatitis C recurrence and validation of non-invasive diagnostic methods of liver fibrosis.

Main lines of research

Treatment of chronic hepatitis C with new direct-acting antivirals: Participation and leadership of international clinical trials for the evaluation of the efficacy and safety of new direct acting antivirals against hepatitis C virus in special populations: decompensated cirrhotics, cirrhotics awaiting liver transplantation and liver transplant recipients.

Immune factors associated with hepatitis C treatment: Antiviral therapy with pegylated interferon and ribavirin is associated with a significant risk of developing bacterial infections in patients with hepatitis C-related cirrhosis. During this year, we have shown that the addition of a protease inhibitor to antiviral therapy further increases the risk of infection. These results have encouraged us to assess the effect of the protease inhibitors on the immune system and, particularly on neutrophil dysfunction.

HCV quasispecies analysis by massive sequencing: We have consolidated an active collaboration with our CIBERehd partners in Vall d'Hebron Institut de Recerca (Barcelona) to study HCV genetic evolution by ultra-deep pyrosequencing (UDPS). In particular, we are interested in the study of HCV quasispecies dynamics in patients that develop very severe forms of hepatitis C recurrence after liver transplantation and in patients undergoing interferon-free treatments.

Acute hepatitis C in HIV-infected patients: The incidence of acute hepatitis C among HIV-infected men who have sex with men (MSM) has significantly increased in recent years. For this reason, during 2014 we established a new research line in collaboration with Dr. Mallolas's team (Infectious Diseases Unit, Hospital Clínic) in order to investigate the dynamics of HCV transmission in an outbreak of acute hepatitis C in HIV-infected MSM in Barcelona by massive sequencing.

Detection of HCV antigens in liver biopsies: We have established and validated an immunohistochemical assay to detect HCV antigens in liver tissue from HCV-infected liver transplant patients in formalin-fixed paraffin paraffin-embedded liver biopsies. This method might be helpful for the diagnosis of severe hepatitis C recurrence after liver transplantation in cases where the histopathological findings are not conclusive.

R & D international competitive projects: We are currently participating in the European project entitled "Human monoclonal antibody therapy to prevent hepatitis C virus reinfection of liver transplants: advancing lead monoclonal antibodies into clinical trial" (Ref. 305500, HepaMAb). The main objectives of this project are:

  1. the preclinical development of two monoclonal antibodies capable of blocking HCV entry into hepatocytes and
  2. the realization of a proof of concept clinical trial for the prevention of graft infection after liver transplantation. This consortium is composed of 7 European partners from different areas: industry, academia, research institutes and hospitals.