Novel drug discovery strategies for the treatment of decompensated cirrhosis.

INTRODUCTION:Disease progression in cirrhosis leads to decompensation and acute-on-chronic liver failure (ACLF), which is characterized by organ failure and high mortality. Portal hypertension and cardiovascular dysfunction trigger the development of cirrhosis-related complications whilst tissue injury and cellular metabolic dysfunction lead to organ failure. System inflammation is the overarching mechanism mediating both the transition from compensation to decompensation as well as progression to ACLF. Treatment of precipitating events and intensive organ support is the only established therapeutic strategies. Liver transplantationrepresents the only curative therapy but contraindications and organ scarcity limit its availability to only a minority of patients with end-stage liver disease. Therefore, the discovery and development of novel interventions modifying the disease course and improving patients' outcome are of utmost importance. AREAS COVERED:This review highlights and discusses therapeutic novelties in the field of end-stage liver disease. EXPERT OPINION:Despite decades of research, there are still no established therapies to improve the devastating prognosis of patients with end-stage liver disease. The clinical heterogeneity and complex pathogenesis will put high demands on drug discovery. Combinatorial therapies tailored to the patients' individual pattern of pathomechanisms may be the most efficient way to modify disease course.