Novel approaches and therapeutics in acute‐on‐chronic liver failure

1. Acute-on-chronic liver failure (ACLF) is a newly defined syndrome. 2. Its diagnosis is made using the CLIF Organ Failure Score. 3. The prognosis of ACLF is made using the CLIF ACLF score. 4. Treatment options are currently limited to supportive care. 5. New therapies are being developed based on better understanding of its pathophysiology. Acute-on-chronic liver failure (ACLF) in cirrhosis has recently been characterized by the CANONIC study as a highly prevalent syndrome consisting of acute decompensation (AD), organ/system failure(s), and high 28-day mortality (32%). Until the publication of the CANONIC study, conventional scoring systems developed to define the prognosis of patients with cirrhosis, such as the Child-Pugh and Model for End-Stage Liver Disease (MELD) scores or their variations, were the only tools available to prognosticate in this patient cohort. They were limited in their prognostic accuracy in ACLF due to a failure to incorporate 2 central prognostic determinants: extrahepatic organ failures and measures of systemic inflammation, which fundamentally underlie the pathophysiological basis of the syndrome. The CANONIC study was a large-scale multicenter prospective clinical study evaluating over 1300 patients hospitalized with a complication of cirrhosis and was conducted to describe the clinical phenotypes of patients with ACLF. A further specific aim of the study was to assess the currently available prognostic scoring systems and develop a new score if required. Indeed, the aims of the study were met and led to the description of the ACLF phenotype and the development and validation of novel scoring systems for the prognosis of patients with ACLF and AD. The resultant CLIF Consortium (CLIF-C) ACLF score has since been independently validated with proven superior prognostic accuracy for ACLF compared with conventional measures such as the MELD and ChildPugh scores. The temporal clinical course of these patients was identified as an important prognostic indicator, and dynamic assessment of the patient’s clinical course using these scoring systems has also been validated as an important prognostic tool. This article will consider the phenotype of ACLF and AD and how the nature of this influences Abbreviations: ACLF, acute-on-chronic liver failure; AD, acute decompensation; CLIF-C, CLIF Consortium; FiO2, fractional inspired oxygen; I, injury, precipitating event; INR, international normalized ratio; MAP, mean arterial pressure; MELD, Model for End-Stage Liver Disease; O, type and number of organ failures; P, predisposition; PaO2, partial pressure of oxygen; PIRO, predisposition injury response organ; R, response; SOFA, Sequential Organ Failure Assessment; SpO2, oxygen saturation.