How should acute‑on‑chronic liver failure be managed in a patient with known cirrhosis who develops rapid deterioration of liver function and multi‑organ failure?

Management of Acute-on-Chronic Liver Failure

Patients with cirrhosis who develop ACLF require immediate ICU-level care focused on identifying and treating precipitating events (especially infection), providing aggressive organ support, and urgent evaluation for expedited liver transplantation in selected candidates. 1

Initial Recognition and Assessment

Diagnostic Framework

ACLF is defined by three critical components that must be present simultaneously: 1

• Liver failure (elevated bilirubin and INR) in a patient with chronic liver disease
• Acute onset with rapid deterioration in clinical condition
• At least one extrahepatic organ failure (neurologic, circulatory, respiratory, or renal)

The 28-day mortality ranges from 30-50%, driven primarily by the number and severity of organ failures. 1 Traditional MELD and MELD-Na scores significantly underestimate mortality in ACLF because they fail to capture extrahepatic organ dysfunction. 1

Prognostic Scoring

Use ACLF-specific scoring systems rather than MELD alone: 1

• NACSELD ACLF score includes advanced extrahepatic organ failure, age, MELD, WBC count, and serum albumin at admission
• CLIF-C ACLF score incorporates hepatic and extrahepatic organ failures with age and WBC count, can be calculated serially
• MELD-Lactate provides excellent prognostic accuracy and may outperform MELD alone

Immediate Management Priorities

Identify and Treat Precipitating Events

Infection is the most common precipitant (48% of cases) and must be aggressively sought and treated. 1, 2

Key precipitants to evaluate systematically: 2

• Bacterial infections with sepsis (most common identifiable cause)
• Active alcoholism and severe alcohol-associated hepatitis
• Drug-induced liver injury
• Gastrointestinal hemorrhage (particularly variceal bleeding)
• Acute kidney injury and electrolyte disorders
• Recent surgery or procedures

Critical caveat: Nearly 40-48% of ACLF cases have no identifiable precipitant, but this should never delay aggressive management. 2, 3

Infection Management Protocol

Maintain high suspicion for sepsis because traditional markers are unreliable in cirrhosis: 1

• Lactate clearance is impaired by liver dysfunction
• Vasodilator production from portal hypertension lowers MAP
• Alcohol-associated hepatitis elevates WBC and inflammatory markers
• Fever is often absent in cirrhotic patients with sepsis

Diagnostic approach: 1

• Obtain cultures (blood, urine, ascitic fluid) immediately
• Start empiric broad-spectrum antibiotics without waiting for culture results
• Consider nosocomial infections, MDR organisms, and fungal infections in patients not responding to initial antibiotics
• Nosocomial and MDR infections are particularly associated with poor outcomes

Organ-Specific Support

Renal Failure Management

For hepatorenal syndrome-acute kidney injury (HRS-AKI): 1, 4

First-line pharmacotherapy:

• Terlipressin (0.85 mg IV every 6 hours, increase to 1.7 mg every 6 hours on Day 4 if creatinine decreased <30% from baseline) plus albumin (1 g/kg on Day 1, maximum 100g, then 20-40 g/day) 4
• Norepinephrine can be used as alternative to terlipressin, may be preferred in patients with shock 1

Renal replacement therapy (RRT): 1

• Reserve for patients with HRS-AKI who failed pharmacotherapy
• Primarily indicated for patients listed or being considered for liver transplantation
• Use should be individualized based on transplant candidacy

Cardiovascular Support

Target appropriate mean arterial pressure with vasopressors while avoiding excessive volume expansion. 5 The optimal MAP threshold and vasopressor choice remain areas of active investigation, but maintaining adequate perfusion pressure is critical for preventing further organ injury.

Respiratory Support

Provide oxygen therapy and ventilation for respiratory failure, with special attention to: 5

• Preserving airway patency to prevent aspiration pneumonia
• Consider low tidal volume and low PEEP strategies in mechanically ventilated patients
• Noninvasive ventilation when appropriate before escalating to intubation

Hepatic Encephalopathy

Treat early with standard therapy (lactulose, rifaximin) to prevent aspiration pneumonia and further neurologic deterioration. 5

Coagulation Management

Provide substitutive therapy only for clinically significant bleeding, not for laboratory values alone. 5 Viscoelastic testing (TEG/ROTEM) may guide transfusion decisions better than traditional coagulation parameters.

Liver Transplantation Evaluation

Expedited liver transplantation may be indicated in selected ACLF patients, though specific predictors of acceptable outcomes remain uncertain. 1

Transplant Candidacy Assessment

Early referral to transplant centers is strongly recommended for: 5

• Patients with ACLF Grade 2-3
• Rising bilirubin despite supportive care
• Progressive organ failures

Futility considerations: 1, 5

• Decisions about futility should be based on candidacy for expedited transplantation, available resources, and potential reversibility of ACLF
• For non-transplant candidates with four or more organ failures after one week of adequate intensive treatment, withdrawal of intensive care support can be considered

Palliative Care Integration

Palliative care consultation should be incorporated early into the management of critically ill cirrhotic patients. 1 This is associated with:

• ~50% lower readmission rates
• Shorter length of stay
• Cost savings of approximately $10,000 per patient
• Doubled chance of hospice discharge when appropriate

The common pitfall is consulting palliative care too late—it should be considered early in the disease course, not just at end-of-life.

Special Considerations

Plasma Exchange

Plasma exchange is NOT routinely recommended for ACLF outside research trials. 6 It may be considered only in highly selected critically ill patients as a bridge to transplantation when standard therapies fail and at centers with PLEX expertise. 6

Monitoring and Reassessment

ACLF is a dynamic condition requiring frequent reassessment: 5

• Monitor organ function (liver, kidney, brain, lung, coagulation, circulation) serially
• Reassess for new organ failures and infectious complications
• Serial risk assessment using ACLF-specific scores guides ongoing management decisions

Multidisciplinary Approach

Management is best accomplished by multidisciplinary teams with expertise in critical care, hepatology, and transplant medicine. 7, 8 These patients require enhanced or intensive care unit settings with capability for advanced organ support and rapid access to transplant evaluation. 3