From the Guidelines
The fundamental keys in the diagnosis and treatment of Acute-on-Chronic Liver Failure (ACLF) include early recognition, prompt identification of precipitating factors, and aggressive supportive care, with a strong emphasis on organ failure assessment and management, as outlined in the most recent guidelines 1. The diagnosis of ACLF requires identifying acute decompensation in a patient with pre-existing chronic liver disease, along with organ failure assessment using scoring systems like CLIF-SOFA or MELD.
- Key components for the definition of ACLF include acute onset with rapid deterioration in clinical condition, the presence of liver failure defined by elevated bilirubin and elevated INR in patients with chronic liver disease with or without cirrhosis, and the presence of at least one extrahepatic (neurologic, circulatory, respiratory, or renal) organ failure 1. Treatment should begin with identifying and addressing precipitating factors such as alcoholic hepatitis, viral hepatitis, or bacterial infections.
- For infections, early use of antibiotics is recommended to improve survival rate, and nucleos(t)ide analogues (NAs) should be started immediately in patients with HBV-related ACLF 1. Management of complications is crucial:
- For hepatic encephalopathy, lactulose may be used,
- For ascites, sodium restriction and diuretics may be employed,
- For variceal bleeding, terlipressin or octreotide with endoscopic therapy may be considered,
- For renal dysfunction, albumin and potentially renal replacement therapy may be required 1. The use of viscoelastic testing to assess coagulation function, teripressin combined with albumin for hepatorenal syndrome, and early initiation of CRRT therapy for urgent cases are also recommended 1. Nutritional support with 35-40 kcal/kg/day and 1.2-1.5g/kg/day protein is essential.
- Liver transplantation evaluation should be considered early for eligible patients, as it represents the definitive treatment for those who don't respond to medical management, with an early assessment for liver transplantation proposed for all patients with severe ACLF (ACLF-2 O-3) 1.
From the Research
Fundamental Keys in Diagnosis of ACLF
- Acute decompensation, organ failure(s), and high short-term mortality are key characteristics of ACLF 2
- Organ failure(s) is defined by the Chronic Liver Failure-Sequential Organ Failure (CLIF-SOFA) score or by its simplified version Chronic Liver Failure-Organ Failure Assessment (CLIF-OF) score 2
- ACLF is often triggered by ongoing alcohol consumption, gastrointestinal bleeding and/or infections, and is pathophysiologically characterized by uncontrolled systemic inflammation coupled with paradoxical immunoparesis 3
- Patients with ACLF require prompt and early recognition, and management requires extensive utilization of clinical resources often including escalation to intensive care 3
Fundamental Keys in Treatment of ACLF
- Management of ACLF is broadly focused on supportive care often in an intensive care setting with liver transplantation proving to be an increasingly relevant and effective rescue therapy 3, 4
- Liver transplantation (LT) remains the only potential curative treatment that improves survival of ACLF patients 5
- Prevention of sepsis, support of organs and management of organ failure (commonly hepatic, renal, cerebral, coagulation) and early referral for transplant is crucial 6
- Aggressive multidisciplinary approach can lead to a transplant-free survival in nearly half of the cases 6
- The APASL ACLF research consortium (AARC) liver failure score is a dynamic prognostic model for management decisions and is superior to existing models 6
Stages of ACLF
- ACLF is graded into three stages: ACLF-1 = single renal failure or single nonrenal organ failure if associated with renal dysfunction and/or cerebral dysfunction; ACLF-2 = two organ failures; and ACLF-3 = three to six organ failures, with increasing 28-day mortality rate (from 23%-74%) 2