ACG publishes guidelines for acute-on-chronic liver failure
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The ACG published guidelines for the preferred management of acute-on-chronic liver failure, which has emerged as a major cause of mortality worldwide, in the American Journal of Gastroenterology.
“The guidelines by the ACG are among the first by a [gastrointestinal] society on [acute-on-chronic liver failure (ACLF)] and provide an up-to-date summary of the field and where we need to go from here,” Jasmohan S. Bajaj, MD, MS, professor of gastroenterology, hepatology and nutrition at Virginia Commonwealth University and McGuire VA Medical Center, both in Richmond, Virginia, told Healio. “It spans several important issues that face clinicians especially related to diagnosis, precipitants, management and role of liver transplant in ACLF. The need for better biomarkers and prognosticators is further underlined.”
The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) process was used to determine the quality of evidence for the guidelines. Bajaj and colleagues also created “key concept” statements using expert consensus when evidence was not appropriate for GRADE.
Among the recommendations for ACLF were:
For brain failure:
The use of short-acting dexmedetomidine for sedation is recommended for shorter time to extubation among hospitalized patients with ACLF.
Patients with cirrhosis and ACLF who require mechanical ventilation should not be listed for liver transplant (LT) to improve mortality.
For kidney failure:
IV albumin and vasoconstrictors should be used in patients with cirrhosis and stages 2 and 3 acute kidney injury (AKI), compared with albumin alone, in order to improve creatinine.
Biomarkers should not be used to predict development of renal failure among patients with cirrhosis.
Terlipressin or norepinephrine should be used to improve renal function in hospitalized patients with cirrhosis and HRS-AKI without high grade of ACLF.
For respiratory failure:
Prophylactic antibiotics are not recommended in ventilated patients with cirrhosis to reduce mortality or duration of mechanical ventilation.
For coagulation failure:
Transfusion should not be used in the absence of bleeding or planned procedure in patients with ACLF and altered coagulation parameters.
There is an increased risk of venous thromboembolism in patients with cirrhosis compared with noncirrhotic patients.
For infections:
Early treatment with antibiotics to improve survival is recommended in patients with cirrhosis and suspected infection. The development of ACLF and increased mortality is correlated with infection among hospitalized decompensated cirrhotic patients.
Proton pump inhibitors should be avoided in patients with cirrhosis unless there is clear indication for them because they increase the risk of infection.
For nosocomial and fungal infections:
Suspicion of a resistant organism or fungal infection is suggested to improve infection detection among hospitalized patients with ACLF who have not responded to antibiotics.
For alcohol-associated hepatitis:
In patients with severe alcohol-associated hepatitis, the use of prednisolone or prednisone (40 mg per day) orally is recommended to improve 28-day mortality. However, pentoxifylline is not suggested to improve 28-day mortality.
For management:
The use of granulocyte colony-stimulating factor to improve mortality is not suggested in patients with cirrhosis and ACLF.
The routine use of parenteral nutrition, enteral nutrition or oral supplements to improve mortality is not suggested in hospitalized patients with cirrhosis. In addition, daily infusion of albumin to maintain albumin greater than 3 g/dL is not suggested to improve mortality or prevent renal dysfunction or infection.
For transplant vs. futility:
Patients with cirrhosis and ACLF should not be listed for LT to improve mortality if they continue to require mechanical ventilation.
Early goals of care discussion and referral to palliative care to improve resource utilization should be considered in patients with end-stage liver disease admitted to the hospital.
In addition to these guidelines, health care providers should consider patient-specific medical comorbidities, health status and preferences to “arrive at a patient-centered care approach,” Bajaj and colleagues wrote.
Perspective
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Christina C. Lindenmeyer, MD
In January, the ACG published the first major society guidelines on the optimal management of ACLF. Associated with multiple organ failures in patients with chronic liver disease, ACLF is now widely regarded as an important clinical syndrome associated with significant mortality.
The presentation of this guideline, driven by critical analysis of the available data and expert consensus from Bajaj et al, is particularly important, given the significant heterogeneity in international definitions of ACLF. In support of standardization and to promote increased recognition of the syndrome, the ACG proposed a concise definition for ACLF: “A potentially reversible condition in patients with chronic liver disease, with or without cirrhosis, that is associated with the potential for multiple organ failure and mortality within 3 months in the absence of treatment of the underlying liver disease, liver support or liver transplantation.”
The guideline calls for improved diagnostic markers to better guide management, as well as optimized prognosticative biomarkers. Precipitating factors of ACLF are emphasized, most notably infections (including nosocomial infections), acute alcohol-associated hepatitis, drug-induced liver injury, viral hepatitis and surgical interventions.
The ACG outlines evidence-driven strategies for the management of individual organ failures associated with ACLF, including brain, kidney, lung and circulatory failure.
Finally, the authors provide guidance on specific treatments for ACLF: The importance of multi-disciplinary care, critical care services and transplant hepatology input for patients with ACLF is made paramount. Treatment and reversal of the precipitating injury is critical, in addition to optimized support of associated organ failures. Early liver transplant in select patients provides a mortality benefit, though optimal patient selection is essential. Recognition of futility in patients with a poor prognosis with appropriate referral for palliation is recommended.
Ultimately, the ACG guideline provides guidance on the diagnosis and management of ACLF, as a relatively newly recognized clinical entity. Future directions for research in ACLF shape the conclusion of the guideline, emphasizing the importance of multidisciplinary care coordination, as well as improved education for professionals involved in the care of patients with ACLF.
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