5 liver societies define acute-on-chronic liver failure

Liver doctors worldwide have settled on a single definition for acute-on-chronic liver failure, a common, potentially fatal complication previously defined differently depending on where patients lived.

The American Association for the Study of Liver Diseases (AASLD) announced the framework Oct. 30, saying it worked with four other international liver societies to develop it. Published in Hepatology, the consensus is meant to improve diagnosis, patient care and research around the world, the association said.

Jasmohan Bajaj, a hepatologist and internal medicine professor at Virginia Commonwealth University's School of Medicine, told STAT that uncertainty over the definition had delayed treatment for patients. "The need for it is massive, because patients are suffering with this condition that everyone has their own way of defining," he said.

ACLF occurs when an acute injury makes an existing liver disease worse. In the U.S., that often means cirrhosis that has developed over time suddenly deteriorates because of alcohol or a viral infection.

Some people have had trouble telling ACLF apart from acute liver failure, which develops rapidly in someone who has no underlying illness.

Transplant-list categories

That difference affects transplant priority. Bajaj said patients with acute liver failure receive extra points placing them at the top of the liver transplant list in the U.S. and some Western countries, while those with ACLF currently do not.

"That is why it is very critical for us to define: Where is the line in the sand?" he said.

Bajaj said regional differences in the disease's causes partly explain why definitions varied. East Asia has a lot of hepatitis B, he said, whereas the U.S. has more disease linked to alcohol and a larger population with existing cirrhosis.

The lab measures

The definition uses two lab measures, bilirubin and INR; providers can then check for problems in the brain, kidneys, lungs or circulatory system. Problems in those organs can also indicate liver failure.

Bilirubin is a yellowish pigment left when red blood cells break down, and a liver that is too damaged cannot process it. INR stands for international normalized ratio and measures blood clotting, which depends on proteins produced by the liver.

In May 2026, experts from five liver societies joined pharmaceutical companies and regulators in Barcelona to draft the definition. The Hepatology position paper also gives drugmakers guidance on drug-induced liver injury, transplant and clinical trial endpoints for developing treatments.

Bajaj said the group adapted earlier definitions and tested its thresholds using mortality data at 30 days from several research consortia. "So this was not based on consensus just because we like these cut-offs," he said.

Some issues remained unresolved. Bajaj said some groups proposed dividing ACLF patients further according to whether they had non-decompensated or decompensated cirrhosis. Questions about immune dysfunction and gut failure had not been fully resolved and were left for another time, he said.

"But, by and large, the broad strokes about this were pretty much agreed upon," Bajaj said.

Bajaj said the U.S. Food and Drug Administration also provided input. During its review of the group's work on trial endpoints, the agency had warned the experts, he told STAT: "This may work for your local thing, but if you want to register an intervention, this is not going to be it." He said pharmaceutical companies offered very good unofficial feedback.

Reaching other doctors

Bajaj said the next task is to reach physicians outside liver medicine. He said those doctors should become "force amplifiers for this definition" so patients who are very sick can be moved quickly to a liver transplant center.

"A majority of the countries and places do not have a hepatologist," he said, adding that GI doctors, hospital medicine, emergency, critical care or other specialties handle patients instead.