What is the treatment for ACLF (Acute on Chronic Liver Failure)?

Treatment of Acute-on-Chronic Liver Failure (ACLF)

The treatment of ACLF requires intensive care support with organ-specific interventions, early identification and management of precipitating factors, and timely referral for liver transplantation evaluation in eligible patients. 1

Definition and Recognition

• ACLF is characterized by acute decompensation of cirrhosis with hepatic and extrahepatic organ failures, resulting in high short-term mortality 1, 2
• Multiple definitions exist globally, but all involve acute deterioration in a patient with pre-existing chronic liver disease 1
• Early recognition is critical as ACLF has a dynamic course with rapid progression 1, 3

General Management Principles

• Patients with ACLF should be treated in intermediate or intensive care settings with frequent monitoring of organ function 1
• Management focuses on three key areas:
  1. Organ support
  2. Identification and treatment of precipitating factors
  3. Liver transplantation evaluation 1, 3

Specific Organ Support Strategies

Hemodynamic Support

• Monitor hemodynamic function and administer vasopressors for marked arterial hypotension 1
• Careful fluid management to avoid excessive volume expansion 1

Neurological Support

• Early treatment of hepatic encephalopathy with standard therapy 1
• Protect airway patency to prevent aspiration pneumonia 1
• Monitor for cerebral edema and intracranial hypertension in severe cases 1

Coagulation Support

• Provide substitutive therapy only if clinically significant bleeding is present 1
• Avoid prophylactic correction of coagulation parameters 1

Respiratory Support

• Provide oxygen therapy and ventilation as required for respiratory failure 1

Renal Support

• Identify cause of kidney failure and manage accordingly 1
• For AKI-HRS, treat with terlipressin and albumin or norepinephrine if terlipressin is unavailable 1
• Consider renal replacement therapy for patients with ATN meeting criteria for this treatment 1

Management of Precipitating Factors

Portal Hypertensive Bleeding

• Perform esophagogastroduodenoscopy within 12 hours of presentation for suspected portal hypertensive bleeding 1
• Administer octreotide or somatostatin analogs for portal hypertensive bleeding 1
• Use proton pump inhibitors in patients with portal hypertensive bleeding 1
• Consider transjugular intrahepatic portosystemic shunt (TIPS) for recurrent variceal bleeding after medical and endoscopic intervention 1

Hepatitis B Reactivation

• Promptly administer nucleoside analogs (tenofovir, entecavir) in patients with ACLF due to HBV infection 1

Bacterial Infections

• Early identification and treatment of bacterial infections is crucial 1

Liver Transplantation

• Early referral to liver transplant centers for immediate evaluation is recommended 1
• Liver transplantation in selected patients with ACLF can increase 6-month survival from 10% to 80% 2
• Careful patient selection is necessary as post-transplant complications may be higher in ACLF patients 1

Limitations of Current Therapies

• Extracorporeal liver support systems (MARS, Prometheus) have not shown significant survival benefits in RCTs and are not recommended 1
• N-acetylcysteine use in all forms of ACLF cannot be justified based on current evidence 1
• Systemic corticosteroids are ineffective for ACLF in general 1

Futility Considerations

• Consider withdrawal of intensive care support in patients who are not liver transplant candidates with four or more organ failures after one week of adequate treatment 1
• Patients with CLIF-C ACLF score >70 at admission or day 3 have approximately 90% 90-day mortality 1
• Palliative care consultation should be considered to define prognosis and determine goals of care 1

Future Directions

• Development of specific targeted treatments for ACLF 3, 4
• Standardization of liver transplant candidate selection and prioritization 3
• Better understanding of pathophysiological mechanisms leading to inflammation and organ failures 3, 5