Research lines

  • Clinical, virological and immunological predictors of response after antiviral treatment interruption

    Patients with HBeAg negative chronic hepatitis (the most common in our environment) require a very long antiviral treatment (years, if not for life). The possibility of stopping nucleos(t)ide analog (NUC) therapy in virologically suppressed HBeAg-negative chronic hepatitis B patients has been considered in the recent European clinical guidelines. However, the variables predicting a successful discontinuation of NUC in this population have not been defined yet. Thus, the aim of this research line is to investigate the feasibility of NUC discontinuation in HBeAg-negative patients, with particular emphasis on the role of cccDNA persistence and the impact of immune response alterations in HBV in infection recurrence after treatment interruption.

  • Natural history of chronic HBV infection in inactive carriers and patients in the 'grey zone'

    The 'grey zone' is an ill-defined situation including patients falling between inactive carrier state and HBeAg-negative chronic hepatitis B. Distinction between these 2 categories is relevant due to their different outcomes: inactive carrier patients have a good prognosis, whereas patients with HBeAg-negative chronic hepatitis B may progress to cirrhosis and its complications, and benefit from anti-viral therapy. Despite serial monitoring of serum HBeAg, HBV-DNA, HBsAg and ALT levels has been used for the classification of patients, some subjects still fall into an indeterminate 'grey zone' even after a complete evaluation. To date, appropriate studies on the natural history of patients in the 'grey zone' are not available. The main aim of this research line is to assess the long-term outcomes of 'grey zone' patients compared to inactive carriers in order to elucidate whether these patients simply deserve long-lasting monitoring or need more active intervention remains uncertain.

  • Molecular mechanisms and clinical relevance of the persistence of cccDNA in chronic HBV infection

    The role and regulation of cccDNA in the HBV infection, an episomal replication intermediary that is generated in the nucleus of HBV-infected hepatocytes, is not fully understood yet. The main objectives of this line of research are:

    1. The development and validation of reproducible protocols for the precise detection of cccDNA
    2. The analysis of cccDNA levels during the different stages of the natural history of chronic hepatitis B and its correlation with the clinical and virological parameters and
    3. The establishment of a cell culture system based on a microfluidic bioreactor for the study of HBV infection in vitro
  • Interplay between HBV, HDV and host factors: impact on liver disease progression

    Hepatitis delta is caused by infection with the hepatitis D virus (HDV) and is considered to be the most severe form of human viral hepatitis. Chronic hepatitis delta affects 15-20 million people worldwide (5-10% of the HBV-infected patients) and is the most severe form of human viral hepatitis, with an increased risk of liver cancer and liver-related mortality compared to HBV monoinfection. HDV is a satellite virus requires the envelope proteins of HBV (HBsAg) for its propagation. There is no specific antiviral treatment for acute or chronic HDV infection. Thus, hepatitis delta was designated as orphan disease by the US FDA and EMA. The main objective of this project is to define viral and host factors that contribute to rapid disease progression in HBV/HDV coinfected patients as compared to HBV monoinfected patients. Our data will provide a better understanding of the complex mechanisms involved in HBV/HDV pathobiology and will aid to identify potential strategies for antiviral intervention which in the long term may contribute to improve the clinical management of this special population at risk of severe complications.

  • Efficacy of new antiviral regimens against HCV: relevance of viral and immune factors in liver disease progression

    This line of research is part of “Plan Estratégico Nacional de la Hepatitis C”, a joint effort between the Spanish Health Ministry and various groups from CIBERESP and CIBEREHD. In particular, our main goals are: 1) to investigate the impact of HCV elimination on the natural history of the disease, 2) to analyze the dynamics of resistance-associated variants during therapy with direct-acting antivirals by massive sequencing, and 3) to study of innate and adaptive immune responses in chronic hepatitis C patients receiving direct-acting antivirals.

  • Clinical and biological characterization of patients with Wilson’s disease

    Wilson's disease is a rare hereditary disorder characterized by an abnormal cupper excretion with the consequence of cupper accumulation in the organs. Without treatment, this disease has a fatal outcome. Our team is currently leading a multicentric study for the clinical characterization and follow up of these patients and the development of  a common registry of WD patients in Catalonia. We actively collaborate with neurologists, pathologists and genetists, in order to better define the clinical and biological characteristics of these patients. We participate in phase III studies with new therapies for Wilson's disease.

  • Brain metabolic and functional connectivity dysfunction in patients with chronic hepatitis C and reversibility after viral eradication with direct acting antivirals

    This line of research constitutes the paradigm of an efficient scientific collaboration between our group and the Psychiatric Department. The aim of this approach is to show the impact of viral eradication on the neuropsychiatric dimension after oral treatment with direct-acting antivirals against hepatitis C. To do so, this study, funded by a competitive fellowship obtained in 2017, it is planned to assess different pro-inflammatory systemic cytokines, MRI cerebral changes focused on brain connectivity and metabolites/ neurotransmissions, and by a deep study of psychological analysis of patients before and after therapy.

  • Clinical and virological analysis of population outbreaks of hepatitis A in Barcelona

    Acute hepatitis A is transmitted mainly via the fecal-oral route and/or contaminated aliments. However, several outbreaks in the men who have sex with men (MSM) population classified hepatitis A as a sexually transmitted disease (STD). In this line of research we aim to analyze prospectively all cases of acute hepatitis A registered in Hospital Clínic. Our analyses include evaluations of patients´ demographics data, risk factors, presenting symptoms, sexual orientation, comorbidities and further STD infections. Furthermore, we perform sequencing of the circulating viruses in order to assess the phylogenetic correlation among current and previous circulating strains. In 2017, we characterized a hepatitis A outbreak in Barcelona, affecting primarily the MSM population which was correlated with parallel outbreaks in large European cities.

  • Strategies of hepatitis C microelimination in our geographical area

    Our group is specially interested in the contribution for eliminating hepatitis C infection, following the WHO objectives established for 2030. For this purpose, we are extensively working in epidemiological strategies of screening and treating HCV on different scenarios of high HCV prevalence, such as with people who inject drugs, people with high risk sexual behavior and hospitalized patients at current or past risk of infection.

  • Clinical impact of HCV eradication in patients with advanced liver disease

    • Hepatic and cardiopulmonary hemodynamics: in collaboration with the Hemodynamic Lab in our center we are studying the long-term hepatic and cardiopulmonary hemodynamic effects of viral eradication among patients with clinical significant portal hypertension at baseline as well as the reliability of noninvasive measures for assessing the evolution of liver disease. One of the aims of our research in this field is to perform a patient risk-stratification in order to personalize clinical follow-up after HCV cure.
    • Liver Cancer: we work in close collaboration with the BCLC  group in Hospital Clínic Barcelona to elucidate the impact of HCV eradication with direct acting antivirals on the incidence and recurrence of cancer in patients with advanced liver disease from a clinical, molecular and epigenetic perspective.