Viral, genetic and immune-mediated liver diseases

Problem

Our group has two mains focuses of clinical and translational research: viral hepatitis and autoimmune liver diseases. Viral hepatitis, mainly hepatitis C and B, are relevant causes of cirrhosis, hepatocellular carcinoma, and liver-related mortality worldwide. In the case of hepatitis B virus infection (HBV, with or without HDV), there is no curative treatment, so conducting research in this area is a challenge. We also work on clinical and translational aspects of autoimmune hepatitis and cholestatic liver diseases. In both cases, a better knowledge on the pathophysiology (particularly the adaptive immune responses) will be crucial to advance in future therapies. 

Finally, our team has two other focuses of clinical research: 1) metabolic diseases caused by copper (Wilson’s disease) or iron (hemochromatosis) accumulation, which can evolve into cirrhosis if not diagnosed and treated early and 2) Drug-induced liver injury (DILI), which has an increasing incidence due to the wide use of drugs in the general population.

Approach

In the field of viral hepatitis, advances in the knowledge of the interactions between the virus and the immune responses are key to understand the natural history of the disease and the development of new therapeutic targets. This is particularly relevant in chronic hepatitis B, where an immune exhaustion of T cells may explain the persistence of HBV. Our group is actively working in exploring the mechanisms that explain dysfunctional T and B cells during hepatitis B infection (in the different phases of the disease), by characterizing certain intrahepatic lymphocyte populations, as well as assessing viral replication activity in hepatocytes. Regarding autoimmune hepatitis (AIH), we are working in characterizing peripheral and intrahepatic immune cell populations in newly diagnosed patients and in those who present a flare after withdrawing immunosuppression as a model to better understand the pathogenesis of the disease and the immunological factors that predict treatment response.

In the case of metabolic and drug-induced liver disease, epidemiological studies and the search for factors (genetic or environmental) that are involved in diseases’ outcomes are expanding fields.

Impact

The group has made significant contributions to the study of the impact of curing hepatitis C, especially on the treatment (with direct acting antivirals) in patients with advanced liver diseases and associated extrahepatic manifestations. Currently, we are focused on: 1) analyzing virological and immunological factors involved in the evolution of hepatitis B and their potential use to predict response to therapy, and 2) studying transcriptomic and immunological factors that predict treatment response in patients with AIH to subsequently design an individualized treatment approach with more aggressive immunosuppression being administered to patients with lower changes of response to standard therapy with corticoids and azathioprine.