Liver transplant is the only curative treatment for acute liver failure and end-stage liver disease. Since its main limitation is the scarcity of available organs, a major effort has been made in recent decades to broaden the criteria for the use of organs, including those from elderly donors and/or from cardiac death.
In addition, strategies have also been pursued to improve the quality of these organs and to reduce the risk of their malfunctioning after transplant. However, as life expectancy and the prevalence of obesity and non-alcoholic fatty liver disease (NAFLD) have increased rapidly in the general population, the incidence of donors with steatotic livers has also increased. The relationship between this type of donor and liver transplant outcomes has been associated with a higher rate of early organ dysfunction.
The study, led by Dr Malu Martínez Chantar’s Liver Disease Laboratory (CIC bioGUNE and the Biomedical Research Centre Network for Liver and Digestive Diseases – CIBEREHD), with the collaboration of Dr. Isabel Fabregat’s research group, has characterised the effects of silencing the MCJ protein in preclinical models of ischaemia and reperfusion and liver regeneration. The work has focused on metabolically compromised animals with fatty liver and ageing, as is currently the case in the liver transplant clinic.
In general, liver cell-specific silencing of MCJ increases ATP production and thus prevents characteristic mitochondrial depletion. This improves regenerative impairment and reduces susceptibility to ischaemia of “marginal” organs (steatotic livers or those from very old donors), making them suitable for liver surgery and liver transplantation, says Dr Martínez Chantar.
As Naroa Goikoetxea-Usandizaga, a researcher in the Liver Disease Laboratory at CIC bioGUNE and first author of this study, further explains, “this molecule opens up an unexplored therapeutic window for its use in liver transplantation.”
The article has been contributed to by Dr. Marta Varela, and has been written in collaboration with Dr. Jon Mabe (Tekniker), Dr. Jordi Gracia (IDIBAPS), Dr. Óscar Lorenzo (Jiménez Díaz Foundation – Autonomous University of Madrid), Dra. Paloma Martín-Sanz (Institute of Biomedical Research – IIB), Alberto Sols (CSIC-UAM) Dr. Nicola G A Abrescia (CIC bioGUNE), Dr. Guadalupe Sabio (National Cardiovascular Research Centre – CNIC), Dr. Mercedes Rincón (University of Vermont), Dr. Juan Anguita (CIC bioGUNE), Dr. Eduardo Miñambres (Marqués de Valdecilla University Hospital – IDIVAL), Dr. César Martín (University of the Basque Country – UPV/EHU), Dr. Marina Berenguer (La Fe University and Polytechnic Hospital), Dr. Isabel Fabregat (University of Barcelona, L’Hospitalet and Bellvitge Institute of Biomedical Research -IDIBELL), Dra. Marta Casado (Valencia Institute of Biomedicine, IBV-CSIC), Dr. Carmen Peralta (August Pi i Sunyer Institute of Biomedical Research – IDIBAPS) and other national and international researchers from these institutions.
The Bellvitge Biomedical Research Institute (IDIBELL) is a biomedical research center created in 2004. It is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona and the City Council of L’Hospitalet de Llobregat.
IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centers accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the “HR Excellence in Research” program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Center of the AECC Scientific Foundation (FCAECC).