RESUMEN
Acute-on-chronic liver failure (ACLF) is a clinical syndrome that occurs in patients with cirrhosis and is characterised by acute deterioration, organ failure and high short-term mortality. Alcohol is one of the leading causes of ACLF and the most frequently reported aetiology of underlying chronic liver disease. Among patients with alcoholic hepatitis (AH), ACLF is a frequent and severe complication. It is characterised by both immune dysfunction associated to an increased risk of infection and high-grade systemic inflammation that ultimately induce organ failure. Diagnosis and severity of ACLF determine AH prognosis, and therefore, ACLF prognostic scores should be used in severe AH with organ failure. Corticosteroids remain the first-line treatment for severe AH but they seem insufficient when ACLF is associated. Novel therapeutic targets to contain the excessive inflammatory response and reduce infection have been identified and are under investigation. With liver transplantation remaining one of the most effective therapies for severe AH and ACLF, adequate organ allocation represents a growing challenge. Hence, a clear understanding of the pathophysiology, clinical implications and management strategies of ACLF in AH is essential for hepatologists, which is narrated briefly in this review.
RESUMEN
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.
