P3. Epidemiology, prevention and treatment of hepatitis virus infection

Coordinator: Xavier Forns

Clinical and scientific relevance of the areas covered in the programme

Viral hepatitides are the most frequent cause of acute and chronic liver disease in the world. Three of the five known viruses causing acute hepatitis (HAV, HBV, HCV, HDV and HEV), can cause persistent infection and chronic hepatopathy (HBV, HCV and HDV). In Spain and in the developed countries, the incidence of acute viral hepatitides has dropped drastically in the last 20 years due to the improvement in hygiene conditions, systematic vaccination programmes against HAV and HBV in children, adolescents and risk groups, and systematic screening of blood donors for HBV and HCV.

The epidemiology of infections by HBV, HCV and HDV has nevertheless changed significantly over the last few years all over the European Union mainly due to immigration, the decrease in transmission by transfusions and the maintenance of transmission, especially of HCV, in risk groups. The risk groups include parenteral drug addicts with shared non-disposable material, men having sex with men, prison inmates, and patients subjected to percutaneous or invasive procedures with badly sterilised material and/or insufficient compliance of universal precautions by healthcare staff at centres where there is a large proportion of individuals carrying the infection. In Spain there are two flows of immigrants which mean changes in the epidemiology of infections: the population of sub-Saharan origin and the from Eastern Europe, both areas with very high prevalences of viral hepatitides. For example, the prevalence of infection by HBV and HCV among the 800,000 Romanians resident in Spain is over 5%. As a result of immigration, the distribution of HBV and HCV genotypes has also been modified. The diagnostic and therapeutic implications of genotypic changes are still to be determined.

The prevalence of HCV is 2% in the general population and this has a minimum rate of evolution to cirrhosis of 20% at 20 years from infection. It is estimated that in the last five years over 70,000 persons have been diagnosed with chronic HCV infection. Coinfection of HCV with HIV is another problem of great significance affecting >70% of patients acquiring HCV parenterally. The long survival of HIV + associated with the use of multiple antiretroviral therapy has made terminal chronic hepatopathy by HCV (and/or HBV) the main cause of morbidity and mortality in these patients. It finally proves of interest to stress that today most cases of acute hepatitis are caused by HEV.

Current situation of the research being done

In the field of hepatitis C there has been some very relevant progress in the last two years, with the appearance of direct-acting antivirals which mean that chronic infection can be cured in over 90% of the patients treated. This has enabled treating and eradicating the virus in patients with advanced illness. We do not however know the impact of the eradication of the virus on the natural history of decompensated cirrhosis, as well as on the incidence of hepatocellular carcinoma. What is more, there is no data on the treatment’s impact on the regression of fibrosis in this group of patients. Although the current treatments are highly effective, the appearances of resistance-associated variants (RAVs) is a problem arising in patients with treatment failures. The usefulness of deep sequencing techniques to identify RAVs is another aspect requiring collaborative studies, as it could allow identifying the individuals with a greater risk of recurrence of the infection when they complete the treatment. Another relevant aspect in the field of hepatitis C is the role of the immune system in the eradication of the infection: the presence of RAVs is not universal in those patients who fail the treatment and deficiencies in the innate or acquired immune response could possibly explain some cases of recurrence. Other aspects which deserve attention in the field of  hepatitis C are the study of epigenetic factors in the natural history of the infection, the influence of virus replication in cell metabolism (steatosis, oxidative stress) and the mechanisms that the virus uses to endure in the organism (both the ones due to its genetic variability and those that depend on the use of the host’s mechanisms).  

As regards hepatitis B, it is important to stress that this is an infection that is very hard to eradicate when it has become chronic. Antiviral drugs are able to control viral replication but not to eliminate the virus from the hepatocytes. The persistence of cccDNA in the nucleus of the hepatocytes perpetuates the production of virions and until now it has not been possible to find drugs able to interfere with this structure. One of the scenarios of research in this field is that of therapeutic vaccines or drugs enabling modulating the immune response to the virus.

Program Group Members

Main ResearcherConsortium InstitutionRegionsDetails
José Luis Calleja (grupo vinculado) Universidad de Alcalá Madrid View Group
Juan Ignacio Esteban Fundación Hospital Universitario Vall D´hebron - Institut de Recerca (VHIR) Cataluña View Group
Rafael Esteban Fundación Hospital Universitario Vall D´hebron - Institut de Recerca (VHIR) Cataluña View Group
Xavier Forns (Coordinador de Programa) Hospital Clínico y Provincial de Barcelona Cataluña View Group
Mª Luisa García-Buey Servicio Madrileño de Salud Madrid View Group
Javier García-Samaniego Servicio Madrileño de Salud Madrid View Group
Jordi Gómez Agencia Estatal Consejo Superior De Investigaciones Científicas Granada View Group
Manuel Romero Fundación Pública Andaluza para la Gestion de la Investigacion en Salud Sevilla View Group
Francisco Javier Salmerón Fundación para la Investigación Biosanitaria en Andalucía Oriental (FIBAO) Granada View Group