How to diagnose and manage acute on chronic liver failure?

From the Guidelines

Acute on chronic liver failure (ACLF) should be diagnosed and managed promptly, with a focus on identifying and treating the precipitating factor, providing supportive care, and considering liver transplantation for eligible patients, as recommended by the most recent guidelines from the European Association for the Study of the Liver 1.

Diagnosis of ACLF

Diagnosis involves identifying acute decompensation in a patient with pre-existing liver disease, characterized by jaundice, coagulopathy, and organ failure. Initial assessment should include:

• Liver function tests
• Complete blood count
• Coagulation profile
• Renal function tests
• Imaging studies like ultrasound or CT scan The CLIF-SOFA or CLIF-C ACLF scores help determine severity and prognosis, as noted in the AASLD practice guidance on acute-on-chronic liver failure 1.

Management of ACLF

Management begins with identifying and treating the precipitating factor, such as:

• Alcoholic hepatitis (using prednisolone 40mg daily for 7 days)
• Viral hepatitis (with appropriate antivirals like entecavir 0.5mg daily for HBV)
• Bacterial infections (using broad-spectrum antibiotics like ceftriaxone 1-2g IV daily) Supportive care is crucial and includes:
• Maintaining hemodynamic stability with careful fluid management
• Nutritional support (35-40 kcal/kg/day with 1.2-1.5g/kg/day protein)
• Prevention of complications For hepatic encephalopathy, administer lactulose 25-30ml every 1-2 hours until bowel movements occur, then 15-30ml 2-3 times daily. Manage ascites with sodium restriction (2g/day) and diuretics (spironolactone 100mg with furosemide 40mg daily, adjusting as needed). For hepatorenal syndrome, terlipressin 0.5-2mg IV every 4-6 hours with albumin 20-40g/day is recommended, as suggested by guidelines for the management of adult acute and acute-on-chronic liver failure in the ICU 1.

Consideration for Liver Transplantation

In severe cases, liver support devices like MARS or Prometheus may temporarily bridge to transplantation. Ultimately, liver transplantation remains the definitive treatment for eligible patients with ACLF who don't improve with medical management, offering the best long-term survival, as emphasized by the European Association for the Study of the Liver guidelines 1.

From the FDA Drug Label

Assess Acute-on-Chronic Liver Failure (ACLF) Grade and volume status before initiating TERLIVAZ [see Warnings and Precautions (5.1) and References (15)]. To diagnose acute on chronic liver failure (ACLF), assess the patient's ACLF Grade and volume status before initiating treatment with TERLIVAZ.

• The diagnosis of ACLF is based on the presence of acute deterioration of liver function in a patient with pre-existing chronic liver disease.
• ACLF Grade should be assessed, as patients with ACLF Grade 3 are at increased risk of respiratory failure.
• Volume status should also be evaluated, as patients with volume overload are at increased risk of respiratory failure. 2

From the Research

Diagnosis of Acute on Chronic Liver Failure

• Acute on chronic liver failure (ACLF) is defined as an abrupt and life-threatening worsening of clinical conditions in patients with cirrhosis or chronic liver disease 3.
• The diagnosis of ACLF involves identifying acute decompensation of chronic liver disease associated with organ failures and high short-term mortality 4.
• The Chronic Liver Failure-Sequential Organ Failure (CLIF-SOFA) score or its simplified version Chronic Liver Failure-Organ Failure Assessment (CLIF-OF) score can be used to define organ failure(s) 5.
• ACLF is graded into three stages based on the number of organ failures: ACLF-1, ACLF-2, and ACLF-3, with increasing 28-day mortality rate 5.

Management of Acute on Chronic Liver Failure

• Management of ACLF is currently based on the supportive treatment of organ failures, mainly in an intensive care setting 3.
• Liver transplantation is an effective treatment that offers a good long-term prognosis for selected patients 3, 6.
• Artificial liver support systems can help remove toxins and metabolites and serve as a bridge therapy before liver transplantation 6.
• Hepatic regeneration during ongoing liver failure is possible through the use of growth factors 6.
• Pre-emptive antiviral agents for hepatitis B before chemotherapy to prevent viral reactivation and caution in using potentially hepatotoxic drugs can prevent the development of ACLF 6.

Prognosis and Clinical Characteristics

• The course of ACLF is dynamic and changes over the course of hospital admission, with most patients having a clear prognosis between day 3 and 7 of hospital admission 4.
• Clinical decisions such as evaluation for liver transplant or discussion over goals of care could be tailored using clinical scores 4.
• The development of organ failures may be a result of a combination of tissue hypoperfusion, direct immune-mediated damage, and mitochondrial dysfunction 3.
• An excessive systemic inflammatory response seems to play a crucial role in the development of ACLF 4.