Serum Protein Test Can Predict Outcomes for Liver Failure Patients

The leading cause of acute liver failure (ALF) is acetaminophen, although other factors such as prescription medications, herbal supplements, autoimmunity, and viruses like Hepatitis A and B can also result in the condition. While most patients with acetaminophen-induced ALF recover without needing a transplant, the demand for organs far surpasses the supply. As a result, a prognostic tool is required to distinguish patients who are likely to recover from those who are likely to succumb to ALF. Now, new research findings have emerged that could save lives by providing faster and more accurate identification of hospitalized patients who require liver transplants or are likely to recover.

In a collaborative study, a team of researchers, including investigators at Rutgers University (Piscataway, NJ, USA), performed a retrospective analysis of blood samples and medical records of hospitalized ALF patients. Their study revealed that levels of a serum protein called carbamoyl phosphate synthetase 1 (CPS1), which is short-lived but abundant, can accurately predict patient outcomes - whether they will recover or require a transplant. This team of researchers has already established CPS1's potential as a prognostic tool in previous studies. These studies demonstrated that CPS1 is only present in the blood when liver cells rich in CPS1 are damaged by acute hepatotoxicants. Additionally, the protein has a short half-life, meaning that if a patient's liver begins to recover and cell death slows or stops, CPS1 levels in the blood will decrease within hours. This decrease in CPS1 levels is a strong indication that the patient is likely to recover without requiring a transplant.

In the latest study, researchers performed a review of records and samples from 103 patients suffering from acetaminophen-induced liver failure and 167 patients with liver failure caused by other factors. On average, patients from the first group who received liver transplants or passed away within three weeks of hospitalization had approximately double the amount of CPS1 in their blood compared to those who recovered spontaneously. In the second group, patients who died or underwent transplants also had higher CPS1 levels than those who recovered, with levels about a third higher. However, the researchers determined that there was an 11 percent probability that this was a mere coincidence. Importantly, a greater percentage of patients with acetaminophen-induced ALF who required liver transplantation or passed away had higher levels of CPS1 on day 3 compared to day 1 of hospitalization. This increase in CPS1 was observed, but not in other liver enzymes that usually indicate injury. A subsequent study involving a larger sample of patients will aim to validate these findings in an independent cohort and determine if there is a link between CPS1 and ALF outcomes resulting from causes unrelated to acetaminophen. The follow-up study will also examine whether incorporating CPS1 measurements into current prognostic tools for predicting liver-failure outcomes enhances their accuracy, especially during the first few days following a liver failure or as part of daily CPS1 level monitoring during hospitalization.

“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 management tool for 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 senior author of the study.

“Enhanced diagnostics, like CPS1, that allow earlier decision-making regarding the need for liver transplantation and that improve the predictability of outcome would clearly improve the care of patients with ALF,” added Lu Chen, a visiting scholar at the Rutgers Center for Advanced Biotechnology and Medicine.

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