Systemic inflammation and portal hypertension are key predictors of acute-on-chronic liver failure (ACLF) in the 3 months after a hospital stay for acute decompensated cirrhosis and also of death after 12 months, a preliminary analysis of data from the PREDICT study shows.
“Before this, we never had any patient signatures to identify ACLF,” said Jonel Trebicka, MD, PhD, from the JW Goethe University Hospital in Frankfurt, Germany.
Now, Dr. Trebicka’s team has “characterized the phenotypes in pre-ACLF that will progress within 3 months,” he said in an interview. “Those with high levels of inflammatory proteins, white blood cell count, are more likely to develop ACLF.”
ACLF is a highly complex disorder that can lead liver, cardiovascular, renal, cerebral, pulmonary, intestinal, adrenal, and immune systems to fail, Dr. Trebicka explained when he discussed the analysis – published online in the Journal of Hepatology – during the virtual International Liver Congress (ILC) 2020.
The chance of survival after the onset of ACLF is low – the 28-day survival rate is 30% – and “the only treatment we have is liver transplant,” he said.
For their prospective observational study, Dr. Trebicka and his colleagues assessed 1071 participants from 48 European hospitals in 14 countries who were admitted for an episode of acute decompensation, defined as the development of ascites, hepatic encephalopathy, gastrointestinal hemorrhage, infection, or a combination thereof.
The researchers identified three distinct clinical courses for a patient hospitalized with acute decompensated cirrhosis that will help clinicians predict the development of ACLF.
At study enrollment, more than half of the patients at highest risk for ACLF had pre-ACLF and high-grade systemic inflammation. The patients at intermediate risk had unstable decompensated cirrhosis with low-grade systemic inflammation and complications related to severe portal hypertension. And those at lowest risk for ACLF had stable decompensated cirrhosis and no severe systemic inflammation or portal hypertension complications, and did not develop ACLF or another episode of acute decompensation in the subsequent 3 months.
“There have been hints of possible phenotypes before – for stable and unstable ACLF – but we never had anything specific to diagnose,” Trebicka reported.
“We found that there are two main mechanisms in the development of ACLF that are most important,” he said. The first is systemic inflammation with high levels of proteins, which “leads to organ failure. This is the most striking acute mechanism.”
The second is the development of portal hypertension. “This is slower, but also very important, causing increased pressure in the portal vein, and leading to bleeding if the pressure is too great,” he said.
More tools emerging to help predict ACLF
The Albumin-functionality-test (AFT), which uses serum albumin levels to evaluate liver and kidney function, might also be useful in the prediction of ACLF and 12-month survival, according to a separate study an Italian group presented at the virtual ILC.
“Our main results are that parameters from albumin predict the development of ACLF in acute decompensated patients with the same diagnostic performance as the CLIF-AD score,” said Katja Waterstradt, PhD, from the University of Bologna in Italy.
And when the two tests are combined, diagnostic performance is increased, she added.
Dr. Trebicka has disclosed no relevant financial relationships. Dr. Waterstrand is a researcher for MedInnovation GmbH.
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