From the Journals

New guide for acute liver failure urges early treatment, transplant referral


Acute liver failure (ALF), a rare life-threatening condition, is potentially reversible if recognized and treated early, according to the latest guidelines from the American College of Gastroenterology.

The guidelines emphasize the need for timely transfer to a transplant center for patients who are at risk for poor outcomes.

“We wanted to produce an updated set of ALF guidelines for general gastroenterologists,” said lead author Alexandra Shingina, MD, MSc, Vanderbilt University Medical Center, Nashville, Tenn.

The aim was to “provide a comprehensive review of early evaluation and management of these patients,” she added.

The new guidelines build on previous guidelines produced by the American Association for the Study of Liver Diseases in 2011. The guidelines were published in the American Journal of Gastroenterology.

In 2017, the American Gastroenterological Association issued guidelines specific to the diagnosis and management of acute liver failure.

Siddharth Singh, MD, a gastroenterologist with UC San Diego Health and an author of the AGA guidelines, said the new guidelines will help inform the treatment of ALF. “It is encouraging to see the recent ACG guidelines building on prior guidelines published by the AGA in 2017,” he said.

ALF is typically defined as severe liver impairment and rapid clinical deterioration that, with few exceptions, “occurs in patients with no pre-existing liver disease,” the authors write. It is critical to distinguish ALF from the more common acutely decompensated cirrhosis or acute on chronic liver failure, the guidelines note, because their management differs significantly.

“ALF has a multitude of etiologies and a variety of clinical presentations that can affect virtually every organ system,” the authors write.

The cause of ALF is an essential indicator for prognosis and treatment strategy, especially for liver transplantation. For example, hyperacute ALF is predominantly seen in the setting of viral hepatitis A and E, acetaminophen toxicity, and ischemic injury, they note. Although the hyperacute subtype “carries a high risk for cerebral edema, it has the best prognosis without transplantation,” compared with other forms of ALF.

Before liver transplants, nearly 80% of patients with ALF died from the condition. In the past 20 years, 1- and 5-year survival rates from liver transplants are about 80% and 75%, respectively.

The authors emphasize that it is “imperative for clinicians to recognize ALF early ... because initiation of treatment and transplant considerations could be life-saving.”

Notable new recommendations

To develop the new guidelines, a writing group was assembled that included hepatology experts across a range of practice settings and different stages of their clinical and research careers.

They conducted a literature search of the MEDLINE, EMBASE, and Cochrane Library databases for relevant studies published in English up to January 2022, focusing on the highest quality of evidence, where available. Owing to a lack of solid data, the recommendations are based predominantly on expert opinion, the authors note.

ALF “is a rare entity. Literature reporting on outcomes is sparse and limited to retrospective cases series, with almost no randomized controlled trials available,” Dr. Shingina said.

She and her colleagues developed the recommendations to cover all aspects of ALF management, from initial diagnosis through to system- and etiology-specific management of ALF and liver transplantation.

“One of the new recommendations is the early use of CRRT [continuous renal replacement therapy] in patients with ALF and grade 2 encephalopathy, even in the absence of conventional RRT indications,” Dr. Shingina said.

“Although the evidence is limited, we felt that it was an important point in the multidisciplinary management of complex ALF patients, which can potentially save lives by reducing cerebral edema and allowing for more time if a liver transplant is not readily available,” she said.

She also highlighted a recommendation supporting intravenous N-acetylcysteine use in patients with acetaminophen-induced ALF and pointed out that the routine use of intracranial pressure monitors is no longer recommended “given the lack of literature on improved outcomes.”

Dr. Shingina emphasized that living donor liver transplantation can be considered in patients with ALF who are listed as status 1A priority for transplantation in experienced centers, when deceased donor liver transplantation is not readily available, as can ABO-incompatible grafts in patients who are rapidly declining.

The authors also present a timeline of ALF presentation and investigations.

During the first 2-4 hours after presentation at the emergency department, the patient should undergo initial stabilization and investigations, with a transfer to the ICU for those with grade 2 or higher hepatic encephalopathy. The transplant center should also be contacted during this period, the authors write.

After transfer to the ICU or a transplant center and during hours 4-12 After the initial presentation, patients should undergo intensive monitoring.

Psychiatry, social work, and hepatobiliary surgery consults should also be undertaken to determine the patient’s transplant eligibility, and if eligible, they should be put on a list.

Those who are ineligible for transplant or who show improvements should subsequently receive supportive management.

Overall, Dr. Shingina said that risk stratification and contact with a transplant center for potential transfer is of “utmost importance” for general gastroenterologists working in the community.

She said that either the Kings College Criteria or Model for End-Stage Liver Disease score can be used for prognostication, with a MELD score of 25 indicating worse outcomes.

“These are the patients who would benefit from early transfer to the nearest transplant center,” Dr. Shingina said.


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