Epigenetic-sensitive challenges of cardiohepatic interactions: clinical and therapeutic implications in heart failure...

Heart failure and liver dysfunction can coexist owing to complex cardiohepatic interactions including the development of hypoxic hepatitis and congestive hepatopathy in patients with heart failure as well as 'cirrhotic cardiomyopathy' in advanced liver disease and following liver transplantation. The involvement of liver dysfunction in patients with heart failure reflects crucial systemic hemodynamic modifications occurring during the evolution of this syndrome. The arterial hypoperfusion and downstream hypoxia can lead to hypoxic hepatitis in acute heart failure patients whereas passive congestion is correlated with congestive hepatopathy occurring in patients with chronic heart failure. Nowadays, liquid biopsy strategies measuring liver function are well established in evaluating the prognosis of patients with heart failure. Large randomized clinical trials confirmed that gamma-glutamyltransferase, bilirubin, lactate deihydrogenase, and transaminases are useful prognostic biomarkers in patients with heart failure after transplantation. Deeper knowledge about the pathogenic mechanisms underlying cardiohepatic interactions would be useful to improve diagnosis, prognosis, and treatments of these comorbid patients. Epigenetic-sensitive modifications are heritable changes to gene expression without involving DNA sequence, comprising DNA methylation, histone modifications, and noncoding RNAs which seem to be relevant in the pathogenesis of heart failure and liver diseases when considered in a separate way. The goal of our review is to highlight the pertinence of detecting epigenetic modifications during the complex cardiohepatic interactions in clinical setting. Moreover, we propose a clinical research program which may be useful to identify epigenetic-sensitive biomarkers of cardiohepatic interactions and advance personalized therapy in these comorbid patients.