What are the key points in the diagnosis and treatment of Acute-on-Chronic Liver Failure (ACLF)?

From the Guidelines

Acute-on-Chronic Liver Failure (ACLF) diagnosis and management requires prompt identification of the condition and aggressive supportive care, with the cornerstone of treatment involving identifying and treating the precipitating factor, organ support, and early evaluation for liver transplantation. ACLF is characterized by acute decompensation of pre-existing chronic liver disease with organ failure and high short-term mortality. Diagnosis relies on identifying acute deterioration in liver function (rising bilirubin, INR, and creatinine) in patients with cirrhosis, often using scoring systems like CLIF-SOFA or MELD scores 1.

Key points in the diagnosis and treatment of ACLF include:

• Identifying and treating the precipitating factor, which commonly includes bacterial infections (requiring broad-spectrum antibiotics like piperacillin-tazobactam 4.5g IV q6h or meropenem 1g IV q8h) 1
• Organ support, including vasopressors for hypotension (norepinephrine 0.1-0.5 mcg/kg/min), mechanical ventilation for respiratory failure, and renal replacement therapy for kidney failure 1
• Nutritional support should provide 35-40 kcal/kg/day with 1.2-1.5g/kg/day of protein
• Prophylactic measures include antibiotics for spontaneous bacterial peritonitis prevention (norfloxacin 400mg daily) and lactulose (30ml TID) with rifaximin (550mg BID) for hepatic encephalopathy
• Early evaluation for liver transplantation is essential as it remains the definitive treatment for suitable candidates 1

The pathophysiology involves systemic inflammation, immune dysfunction, and multi-organ failure, making early intervention critical to prevent the cascade of organ failures that dramatically increases mortality. According to the most recent guidelines, nucleos(t)ide analogues (NAs) should be started immediately in patients with HBV-related ACLF 1, and teripressin combined with albumin is recommended for the treatment of ACLF with hepatorenal syndrome 1.

In patients with ACLF, it is essential to monitor organ function, particularly liver, kidney, brain, lung, coagulation, and circulation, frequently and carefully throughout hospitalization, as ACLF is a dynamic condition 1. The use of viscoelastic testing (thromboelastographic/rotational thermoelectrometry [ROTEM]) to assess coagulation function in ACLF patients is also recommended 1.

Overall, the management of ACLF requires a multidisciplinary approach, with prompt identification and treatment of the precipitating factor, organ support, and early evaluation for liver transplantation, to improve patient outcomes and reduce mortality.

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)]. Avoid use in patients with ACLF Grade 3 because they are at significant risk for respiratory failure [see References (15)]. The key points in the diagnosis and treatment of Acute-on-Chronic Liver Failure (ACLF) are:

• Assess ACLF Grade: Assess the grade of ACLF before initiating treatment with TERLIVAZ.
• Volume status assessment: Assess the volume status of the patient before initiating treatment with TERLIVAZ.
• Avoid use in ACLF Grade 3: Avoid using TERLIVAZ in patients with ACLF Grade 3 due to the significant risk of respiratory failure. 2

From the Research

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

• ACLF is a distinct syndrome of liver failure in a patient with chronic liver disease presenting with jaundice, coagulopathy, and ascites and/or hepatic encephalopathy, developing following an acute hepatic insult and associated with high 28-day mortality 3.
• The definition of ACLF lacks global consensus and excludes patients with known distinct entities such as acute liver failure and those with end-stage liver disease 3.
• The APASL ACLF research consortium (AARC) liver failure score is a dynamic prognostic model for management decisions and is superior to existing models 3.

Treatment of ACLF

• Prevention of sepsis, support of organs, and management of organ failure (commonly hepatic, renal, cerebral, coagulation) and early referral for transplant is crucial 3.
• Aggressive multidisciplinary approach can lead to a transplant-free survival in nearly half of the cases 3.
• Management of ACLF in the intensive care unit (ICU) involves rapidly recognizing and treating inciting events and aggressively supporting failing organ systems to ensure that patients may successfully undergo liver transplantation or recovery 4.
• The goals of ICU management of patients suffering ACLF are to rapidly recognize and treat inciting events and to aggressively support failing organ systems 4.

Organ Support and Prognostic Assessment

• Organ support, such as renal replacement therapy, mechanical ventilation, and vasopressor support, may be necessary in patients with ACLF 4.
• Prognostic assessment is critical in determining the likelihood of recovery and the need for liver transplantation 4.
• The role of beta-blockers and transjugular intrahepatic portosystemic shunt placement in the management of ACLF has been characterized, and investigational therapies such as extracorporeal liver support and hepatocyte stem cell therapies have shown promise 5.

Liver Transplantation

• Liver transplantation is an emerging and evolving field in the management of ACLF, and multidisciplinary teams with expertise in critical care and transplant medicine are best equipped to manage these patients 4.
• Data suggest that even patients with 3 or more organ system failures may have a 1-year survival >80% after liver transplantation 5.
• Further efforts are needed to understand the predictors of post-liver transplantation survival to facilitate liver transplantation criteria for ACLF 5.