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Acute-on-chronic liver failure

ACLF is a syndrome characterized by an acute decompensation of chronic liver disease, which is associated with organ failures and high short-term mortality.
The pathophysiology of ACLF involves a state of deregulated inflammation, with an initial cytokine burst presenting as systemic inflammatory response syndrome, progression to compensatory anti-inflammatory response syndrome, and associated immunoparalysis leading to sepsis and multi-organ failure.
The prevalence of ACLF in the US is estimated at 26.4% in hospitalized patients with decompensated cirrhosis.
Disease course
Clinically, it presents with signs of liver failure such as jaundice, encephalopathy, coagulopathy, and ascites, with or without extrahepatic organ failure, including kidney, circulatory, and respiratory that can be complicated by sepsis. The clinical profile of ACLF is complex and can change over the course of hospital admission.
Prognosis and risk of recurrence
The prognosis is generally poor, with substantial short-term mortality.
Key sources
The following summarized guidelines for the evaluation and management of acute-on-chronic liver failure are prepared by our editorial team based on guidelines from the European Association for the Study of the Liver (EASL 2023; 2018), the Society of Critical Care Medicine (SCCM 2023; 2020), and the American College of Gastroenterology (ACG 2022).


1.Screening and diagnosis

As per EASL 2023 guidelines:
Include both patients with and without prior decompensation in the definition of ACLF.
Use organ failures as included in the EASL-CLIF-C criteria for the diagnosis of ACLF.
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2.Classification and risk stratification

Prediction of acute-on-chronic liver failure: use the CLIF-C acute decompensation score sequentially to provide prognostic information regarding 90-day, 180-day, and 365-day mortality in patients without ACLF.
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  • Severity assessment

3.Diagnostic investigations

Evaluation of precipitants: obtain systematic evaluation to identify the most common precipitants, including proven bacterial infection, alcohol-related hepatitis, gastrointestinal hemorrhage with hemodynamic instability, flare of HBV infection, HEV infection, recent use of a drug known to cause cerebral failure, and recent use of a drug known to cause kidney failure, in all patients admitted for ACLF or developing ACLF during hospital stay.
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  • Medication review

  • Viscoelastic testing

  • Coagulation studies

  • Nutritional assessment

  • Evaluation for infection

4.Respiratory support

Supplemental oxygen
Provide supportive care with supplemental oxygen in the management of patients with hepatopulmonary syndrome, pending possible liver transplantation.
Consider using high-flow nasal cannula over noninvasive ventilation in hypoxic critically ill patients with ACLF.

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  • Mechanical ventilation

5.Medical management

General principles, setting of care: admit patients with ACLF requiring close monitoring or organ support to the ICU.
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  • General principles (goals of care)

  • General principles (supportive care)

  • General principles (precautions)

  • Fluid resuscitation

  • Albumin

  • Vasopressors

  • Thromboprophylaxis

  • Antibiotic prophylaxis

  • G-CSF

  • Sedation

  • Management of variceal hemorrhage

  • Management of portopulmonary hypertension

  • Management of vascular complications

  • Management of infection

  • Management of SBP

  • Management of septic shock

  • Management of hepatic encephalopathy

  • Management of AKI

  • Management of beta-blockers

6.Inpatient care

Hemodynamic monitoring
Consider placing an arterial catheter for BP monitoring in patients with ACLF and shock.
Consider obtaining invasive hemodynamic monitoring to guide therapy in patients with ACLF and clinically impaired perfusion.

7.Nonpharmacologic interventions

Nutrition, route of administration, EASL
Prefer oral intake whenever possible. Attempt enteral nutrition, ideally using a nasojejunal tube, if oral intake is not possible. Consider initiating parenteral nutrition if enteral nutrition is not tolerated.
Initiate oral nutrition as soon as possible in patients experiencing variceal bleeding/upper gastrointestinal bleeding. Recognize that enteral nutrition can be used safely.

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  • Nutrition (total calories)

  • Nutrition (proteins)

  • Nutrition (oral supplements)

  • Nutrition (fasting/refeeding)

8.Therapeutic procedures

Blood transfusion: avoid administering transfusions in the absence of bleeding or a planned procedure in patients with ACLF and altered coagulation parameters.

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  • Large volume paracentesis

  • Pleurodesis

  • Extracorporeal liver support

9.Perioperative care

Peri-transplant management: consider administering balanced (or normochloremic) crystalloid solution over normal (hyperchloremic) saline for peri-transplant fluid replacement in liver transplant recipients.
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10.Surgical interventions

Liver transplantation: as per EASL 2023 guidelines, consider obtaining an early assessment for liver transplantation in all patients with severe ACLF (ACLF-2 or -3).
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11.Specific circumstances

Patients with alcohol-associated hepatitis: as per EASL 2023 guidelines, do not use corticosteroids in patients with severe alcohol-related hepatitis and ACLF or uncontrolled bacterial infection.
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  • Patients with HBV infection

  • Patients with AIH