Acute-on-chronic liver failure: Terminology, mech- anisms and management

Acute-on-chronic liver failure is an acute deterioration of liver function manifesting as jaundice and coagulopathy with the development of ascites, with a high probability of extrahepatic organ involvement and high 28-day mortality. The pathogenesis involves extensive hepatic necrosis, which is associated with severe systemic inflammation and subsequently causes the cytokine storm, leading to portal hypertension, organ dysfunction, and organ failure. These patients have increased gut permeability, releasing lipopolysaccharide (LPS) and damage-associated molecular patterns (DAMPS) in the blood, leading to hyper-immune activation and the secretion of cytokines, followed by immune paralysis, causing the development of infections and organ failure in a proportion of patients. Early detection and the institution of treatment, especially in the Golden Window period of 7 days, gives an opportunity for reversal of the syndrome. Scores like the Asian Pacific Association for the Study of the Liver (APASL) ACLF research consortium (AARC) score, a model for end stage liver disease (MELD), and the CLIF Consortium acute-on-chronic liver failure (CLIF-C ACLF) score can help in the prediction of mortality. Treatment strategy includes treatment of acute insult. Patients should be considered for early transplant with MELD score >28, AARC score >10, high-grade hepatic encephalopathy, and in the absence of >2 organ failure or overt sepsis to improve survival of up to 80% at five years. Patients, with no option of transplant, can be treated with emerging therapies like faecal microbial transplant, plasma exchange, etc., which need further evaluation. (Clin Mol Hepatol 2023;29:670-689)

Automated summary

Acute-on-chronic liver failure is a severe condition characterized by liver function deterioration, jaundice, coagulopathy, ascites, and high mortality. It is caused by extensive hepatic necrosis, leading to systemic inflammation, cytokine storm, and organ dysfunction. Patients with increased gut permeability show hyperimmune activation followed by immune paralysis, resulting in infections and organ failure. Early detection and treatment, especially within the golden window period of 7 days, can reverse the syndrome. Mortality prediction scores like APASL ACLF Research Consortium (AARC) score, MELD, and CLIF-C ACLF score can aid in prognosis. Treatment strategies include addressing the acute insult and considering early transplantation for eligible patients. Emerging therapies like fecal microbial transplant and plasma exchange can be considered for non-transplant patients.