The clinical challenges of acute on chronic liver failure.

Acute on chronic liver failure (ACLF) encompasses patients with previously well-compensated liver disease in whom an acute decompensation of liver function occurs because of a precipitating event. There are emerging data on the presentation and course of patients with this profile of liver disease; a clear definition based on precise diagnostic criteria, however, remains difficult to establish. In a high percentage of patients, ACLF is associated with the development of multi-organ failure leading to high in-hospital mortality despite costly intensive care therapy. Liver transplantation remains the only curative therapeutic option for the majority of these patients. Therefore, early identification of the precipitating events inducing ACLF and better understanding of the underlying mechanism are key issues for the prevention and treatment of ACLF. However, although there is increasing evidence that cytokines play a major role in the development of ACLF, the pathophysiology remains complex and poorly understood.