IDIBAPS, Institut d'Investigacions Biomèdiques August Pi i Sunyer

1. Study of host factors in relation to the natural history and treatment response among patients with chronic hepatitis C. In this setting, mention should be made of the studies which the group is carrying out on the influence of polymorphisms of the IL28B gene (which encodes for interferon lambda-3) upon the natural history and antiviral treatment response of chronic hepatitis C (in immune competent individuals and liver transplant recipients). In transplant patients with hepatitis C, our group has shown that the presence of a favorable IL28B polymorphism in the recipient, if associated with the favorable polymorphism in the donor liver, significantly increases the antiviral treatment response (Fig. 1). In the coming months, evaluation will be made of the role of this polymorphism in relation to the natural history of chronic hepatitis C virus infection.

2. Development of models for the in vitro study of the hepatitis C virus (HCV). At present there is only a single model for studying the complete life cycle of HCV. This is a limited model, since it is based on the culture of a single cell line, in which only one viral strain grows. Over the last year we have started the development of new cell culture systems based on different cell lines with incorporated markers, allowing the detection of viral replication and the screening of biological samples with considerable rapidity. The ultimate aim of these studies is to establish one or more HCV culture systems allowing the growth and adaptation of viruses from biological samples, and which are therefore more representative of real life situations.

3. Detection of HCV antigens in liver tissue. This is a project which in a sense represents continuity of the work started in 2008 with the purpose of characterizing the expression of HCV penetration receptors (claudin-1, occludin SR-B1 and CD81). Following completion of this project, we wish to detect viral antigens in liver tissue. While this may seem an easy project, to date it has not been possible to detect these antigens in a reproducible manner. Since we have samples from transplant patients with very high viral loads, and taking advantage of the experience gained over the past years with confocal microscopy and immunohistochemistry techniques, we aim to evaluate the presence of different viral antigens in liver biopsies. Success with the project could have clinical applications in aspects as relevant as the differential diagnosis of rejection and the recurrence of hepatitis C after transplantation.

4. Noninvasive diagnosis of chronic hepatitis C. This is a consolidated line of research within the group. Over the past years, different studies by our group have demonstrated the diagnostic validity of transient elastometry (TE, Fibroscan) in diagnosing advanced liver fibrosis or portal hypertension in patients with HCV infection and subjected to liver transplantation. During 2009 and 2010, other non-invasive markers of liver fibrosis have been evaluated (such as the combination of different serum markers of fibrogenesis). Within a more ambitious project (LiverBiomark) forming part of the Ciberehd, the group has proposed the utilization of metabolomics in an attempt to secure the early identification of those patients with hepatitis C presenting a risk of developing serious forms of the disease (in both immune competent individuals and in liver transplant recipients).

5. Treatment of chronic hepatitis C. Logically, our group continues to focus great effort on improving the efficacy and safety of antiviral therapy in patients with chronic HCV infection. Different aspects are included within this line of research: 1) Participation in clinical trials of new antiviral molecules (in both early stages and in pre-marketing phases); and 2) Study of the predictive factors of treatment response and designing of models allowing a reliable prediction of treatment results – particularly as regards the prediction of infection relapse in patients that have been able to achieve negative conversion of HCV during treatment. In the last year we have found that direct antiviral drug treatment (therefore not requiring interferon) is able to definitively eliminate HCV, and thus heal the chronic infection. This is an important step in the field of hepatitis, which will lead to radical changes in treatment in the next 10 years.