Introduction to Acute-on-Chronic Liver Failure (ACLF)

Acute-on-chronic liver failure (ACLF) is a complex condition that poses significant challenges in the healthcare sector, particularly in intensive care units. Cirrhosis, a chronic liver disease, leads to approximately 800,000 hospitalizations a year in the United States, with a significant portion of these cases requiring intensive care. ACLF is a critical condition that emerges in patients with chronic liver disease, often necessitating urgent medical attention​​.

Understanding the Phases of Cirrhosis and ACLF

Cirrhosis traditionally progresses in two stages: a compensated phase without complications and a decompensated phase with complications like portal hypertension. ACLF represents a rapid and severe progression of cirrhosis, characterized by hepatic and extrahepatic organ failures, which dramatically increase the risk of mortality​​.

Defining ACLF: A Global Perspective

ACLF definitions vary globally, leading to confusion in clinical diagnosis and management. The American Association for the Study of Liver Diseases (AASLD) proposes a unified definition that includes acute onset with rapid deterioration, liver failure indicated by elevated bilirubin and INR, and at least one extrahepatic organ failure​​.

Management Focus: Severe Organ Failure and ICU Care

The AASLD guidance focuses on ACLF patients with severe organ failures who often require ICU-level care. This is particularly relevant for patients fulfilling North American Consortium for the Study of End-Stage Liver Disease (NACSELD) ACLF criteria and advanced stages of Asian Pacific Association for the Study of the Liver (APASL) or European Association for the Study of the Liver (EASL-CLIF) ACLF criteria​​.

Prognosis and Prediction Modeling in ACLF

Predicting the development of ACLF is challenging due to its heterogeneous nature. Studies like the PREDICT study have identified certain characteristics and markers that indicate a higher risk for developing ACLF, such as elevated inflammatory markers and severity scores. However, accurately predicting its development remains a complex task​​.

Assessment Scores for ACLF

Several scoring systems, such as the NACSELD ACLF, CLIF-C ACLF, and APASL AARC scores, have been developed to assess the severity of ACLF. These incorporate factors like organ failures, age, white blood cell count, and serum albumin. The importance of lactate as a prognostic marker has also been recognized, with MELD-LA being an excellent predictor of in-hospital mortality​​.

Guidance Statements for Prognosis Assessment

The AASLD recommends using scores that account for both hepatic and extrahepatic organ failures to assess prognosis in critically ill patients with cirrhosis and ACLF. Serial calculation of these scores is suggested for further assessment of prognosis among hospitalized ACLF patients​​.

Organ-Specific Management Recommendations

Managing Brain Failure

Brain failure in ACLF is often due to hepatic encephalopathy (HE). The West Haven HE criteria and the Glasgow Coma Scale are essential tools for characterizing brain failure. Managing HE involves investigating and treating potential precipitants and empirical therapy. The use of lactulose, polyethylene glycol, and other medications like rifaximin should be considered based on the severity of HE​​.

Cardiovascular Failure

Cardiovascular management in ACLF includes assessing volume status and cardiac function. Balanced crystalloids and albumin are recommended for fluid resuscitation. Vasopressors like norepinephrine may be required to maintain end-organ perfusion in shock states. Monitoring hemodynamics is crucial to guide therapy and avoid overresuscitation​​.


ACLF is a critical condition that requires an informed and nuanced approach to management. Understanding the various stages of cirrhosis, recognizing the signs of ACLF, and utilizing appropriate scoring systems for prognosis are crucial. Effective organ-specific management strategies, particularly for brain and cardiovascular failures, are key to improving patient outcomes. This comprehensive guide emphasizes the importance of a tailored approach in the management of critically ill patients with cirrhosis, underlining the complexity and severity of ACLF.


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