Nearly 3,000 Americans are diagnosed with acute liver failure, or ALF, each year. While acetaminophen overdose is often associated with this condition, prescription medications, herbal supplements and viruses like hepatitis A and B can yield the same results. 

“Most individuals with acetaminophen-associated ALF can recover without a liver transplant,” said Robert Fontana, M.D., professor of internal medicine and transplant hepatology researcher at Michigan Medicine. “But it’s no surprise that there’s a tremendous need for transplant organs that far exceeds what’s actually available.”

But recent findings from Fontana and a team of fellow experts from Rutgers University, the University of Texas Southwestern Medical Center and the Medical University of South Carolina may enable a faster and more accurate way to identify patients who are hospitalized and in need of liver transplants or are likely to recover. Their research was recently published in Clinical Gastroenterology and Hepatology.

Their study, which involved a retrospective analysis of blood samples and medical records from 270 patients who were admitted to the hospital with acute liver failure, revealed that concentrations of a short-lived and abundant serum protein called carbamoyl phosphate synthetase 1, or CPS1, helped predict which patients survived without a liver transplant.

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“Any prognostic tool that helps distinguish patients likely to recover from those likely to die from ALF, while transplant candidates are still healthy enough to survive surgery, is extremely valuable,” said Fontana, who is also a leading investigator in the study of acute liver failure and drug-induced liver injury. “That’s why this work is so important.”

The same team of researchers has systemically established CPS1’s potential as such a tool. Their previous work has shown that the protein only reaches the blood when acute hepatotoxicants damages CPS1-rich liver cells that then leads to its release into blood.

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Previous studies also show that the protein has a short half-life. If the liver starts recovering and cell death slows down or stops — a strong indication that a patient will survive without a transplant — blood-borne CPS1 decreases rapidly within hours.

“In this study, we reviewed records and samples from 103 patients with acetaminophen-induced liver failure and 167 with liver failure from other causes,” said Fontana. “Patients from the first group who received liver transplants or died within 21 days of hospitalization had, on average, about twice as much CPS1 in the blood as those who spontaneously recovered.”

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Fontana notes that patients from the second group who died or received transplants also had higher CPS1 levels than those who recovered: “Notably, about a third higher. However, we calculated an 11% chance that this was a coincidence.”

The team’s research also revealed an increase of CPS1 when comparing day three with day one of hospitalization, but other liver enzymes that are normally followed indicators of injury, were not found in a higher percentage of patients with acetaminophen-induced acute liver failure who died or required liver transplantation.

“We still need to validate these results in more patients to further confirm that CPS1 levels predict ALF from causes other than acetaminophen,” said Bishr Omary, senior vice chancellor for academic affairs and research at Rutgers Biomedical and Health Sciences and senior author of the study. “But this has the potential to be a highly valuable prognostic and clinical management tool for acetaminophen and other causes of liver failure.”

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Paper cited: “The role of CPS1 as a prognostic biomarker in patients with acetaminophen induced acute liver failure,” Clinical Gastroenterology and Hepatology. DOI: 10.1016/j.cgh.2023.03.002