Concession of a Health Research Fund FIS project to the Transplant and Autoimmunity group

30 de September de 2019

The research project led by Dr. López Hoyos (Transplant and Autoimmunity group) entitled “Prevalence of post-transplant solid organ non-alcoholic steatohepatitis. Involvement of the innate and adaptive immune response” has obtained funding from the Carlos III Health Institute in the last call of the recently resolved National Plan.

The prevalence of fatty liver disease (NAFLD) is increasing exponentially in our environment, largely associated with the lifestyle of obesity and diabetes. A small percentage will develop non-alcoholic steatohepatitis (NASH) with the associated risk of fibrosis and progression to liver failure that will necessitate liver transplantation. NASH has become an increasing indication of liver transplantation, surpassing even alcoholic liver disease. 

The incidence of NAFLD and its progression to NASH may be increased in liver transplants, but also in another type of solid organ transplant where it has not been taken into account to date. This increase may be conditioned by classic risk factors of metabolic NAFLD (insulin resistance, accumulation of short chain fatty acids, oxidative stress and mitochondrial dysfunction). All of them, together with a pro-inflammatory state, converge in a “multiple hit” that contributes to liver damage and inflammation. 

In the context of solid organ transplantation, a pro-inflammatory state dependent on the allogeneic response coexists against the graft counteracted by the immunosuppressive therapy administered. An alteration of this balance towards an inflammatory state can favor the development of NASH independent of the classic metabolic picture. The definition of phenotypic and functional profiles of the immune response in long-term solid organ transplants with NASH and differentiated clinical phenotypes (with metabolic syndrome or not) can help identify immunological factors related to liver damage risk and its involvement with treatment. immunosuppressant The funded work aims to investigate the role of fatty liver in all types of solid organ transplantation and detect possible immunophenotypes that allow differentiating a different progression. The work team is multidisciplinary and combines expert clinical researchers in the field of transplantation together with researchers with a more basic profile (immunologists) and epidemiologists that facilitates the possible translation of the expected results.

The work is part of the group's strategy of “individualizing” drug immunosuppression. Thus, the finding of immunological profiles associated with the development of NAFLD and its relationship with the different immunosuppressants received may contribute to this individualization and may even allow new therapeutic approaches. In addition, the study of soluble populations and mediators of the blood immune response is likely to identify biomarkers of clinical utility in the management of the development of NAFLD and NASH in transplant patients. The thematic will allow to advance in the line of work of the multidisciplinary group in NAFLD and NASH that has begun to work in the Marqués de Valdecilla University Hospital.