Acute-on-chronic liver failure: From definition to pathogenesis and therapy

The concept of acute-on-chronic liver failure (ACLF) has been widely accepted around the world since it was proposed nearly 30 years ago, but there are still no universal criteria for the definition and diagnosis of ACLF worldwide. In recent years, the key clinical features for describing ACLF, such as the underlying chronic liver diseases, acute intrahepatic or extrahepatic insults, acute hepatic decompensation, extrahepatic organ failure, short-term high mortality, and the reversible course of the disease, have gradually narrowed the differences and reached a consensus. The pathogenesis of ACLF has not been fully elucidated, and most relevant studies focus on systemic inflammation and immune dysfunction. In this review, we discuss the evolution in the clinical definition of ACLF during the last few years and suggest clear criteria for ACLF diagnostics. In addition, we summarize the current understanding of ACLF pathogenesis and review the latest therapeutic targets against this condition. Lastly, we present a novel experimental mouse model that has been proven to be instrumental for the assessment of novel potential therapies for ACLF.