The findings by researchers at Rutgers, the University of Michigan, the University of Texas Southwestern and the Medical University of South Carolina could save lives by allowing faster and more accurate identification of hospitalized patients who need a liver transplant or are likely to recover.
A retrospective analysis of blood samples and medical records from 270 patients admitted to hospital with acute liver failure (ALF) found that concentrations of a short-lived but abundant serum protein called carbamoyl phosphate synthetase 1 (CPS1) helped predict which patients would survive or die without a transplant.
We still need to validate these results in more patients to further confirm that CPS1 levels predict ALF from causes other than acetaminophen (Tylenol), but this has the potential to be a highly valuable prognostic and clinical tool for managing acetaminophen and other causes of liver failure. said Bishr Omary, senior vice chancellor for academic affairs and research at Rutgers Biomedical and Health Sciences and lead author of the study, just published in the journal Clinical Gastroenterology and Hepatology.
About 3,000 Americans suffer from acute liver failure each year, according to the New England Journal of Medicine. Acetaminophen is the most common cause, but other causes include prescription drugs, herbal supplements, autoimmunity, and viruses such as hepatitis A and B.
Most patients with acetaminophen-associated ALF recover without a transplant, but the need for transplanted organs far exceeds the supply. Last year, 214 out of 9,528 patients with acute liver failure received liver transplants.
“Any prognostic tool that helps distinguish patients who are likely to recover from those who are likely to die of ALF — while transplant candidates are still healthy enough to survive surgery would thus be extremely valuable,” said Robert Fontana, professor of internal medicine and director of the Transplant Hepatology Fellowship Program at the University of Michigan, a co-author of this study and a leading researcher in the study of ALF and drug-induced liver injury.
The same team of researchers systematically demonstrated the potential of CPS1 as such a tool. Their previous work showed that the protein only enters the blood when acute hepatotoxic agents damage CPS1 rich liver cells.
Previous studies also show that the protein has a short half-life. If the liver begins to recover and cell death slows or stops a strong sign that the patient will survive without a transplant blood borne CPS1 will decrease within hours.
In the latest study, researchers reviewed records and samples from 103 patients with acetaminophen-induced liver failure and 167 with liver failure from other causes. Patients in the first group who underwent a liver transplant or died within 21 days of hospitalization had, on average, about twice as much CPS1 in their blood as those who recovered spontaneously.
Patients in the second group who died or received a transplant also had higher levels of CPS1 than those who recovered, about a third higher, but the researchers calculated an 11 percent chance that this was a coincidence.
Notably, elevations in CPS1 compared with day 3 versus day 1 of hospitalization, but not other liver enzymes that normally indicate injury, were found in a higher percentage of patients with acetaminophen-induced ALF who died or required liver transplantation.
A follow-up study in more patients will seek to confirm the findings in a separate cohort of patients and determine with greater certainty whether there is an association between CPS1 results and ALF from causes unrelated to acetaminophen.
A follow-up study will also seek to confirm another major finding of the new paper: Adding CPS1 measurement to existing tools for predicting outcomes in patients with liver failure improves their accuracy, especially in the first days after liver failure or as part of daily assessment of CPS1 levels during hospitalization.
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