Study may accelerate identifying patients who need liver transplants

Measuring blood levels of a short-lived protein helped predict which patients would survive without the help of a transplant

9:15 AM

Author | Jina Sawani

liver drawing red and green
Getty Images

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.

SEE ALSO: Many Popular Dietary Supplements Can Yield Dangerous Liver Results (

“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.

SEE ALSO: Liver Damage More Commonly Due to Malignant Tumors than Cancer Immunotherapy Drug (

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.”

SEE ALSO: Liver Transplant Recipient Fights Off COVID-19 (

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.”

SEE ALSO: Antibiotics Side Effects: Drug-Induced Liver Injury from Z-Paks (

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

More Articles About: All Research Topics Industry DX Liver Disease Liver Conditions & Procedures Lab Tests Liver Transplant
Health Lab word mark overlaying blue cells
Health Lab

Explore a variety of healthcare news & stories by visiting the Health Lab home page for more articles.

Media Contact Public Relations

Department of Communication at Michigan Medicine

[email protected]


Stay Informed

Want top health & research news weekly? Sign up for Health Lab’s newsletters today!

Featured News & Stories smart watch on wrist
Health Lab
Clinical smart watch finds success at identifying atrial fibrillation
A Michigan Medicine research team developed a prescription wristwatch that continuously monitors the wearer’s heart rhythm and uses a unique algorithm to detect atrial fibrillation. The clinical-grade device, called the Verily Study Watch, proved very accurate at identifying atrial fibrillation in participants.
sketched out bacteria in a dish yellow and blue colors of U-M
Health Lab
This gross mixture has big benefits for the study of bacteria
Michigan Medicine researchers have found that growing bacteria on agar mixed with organs is an efficient and effective way to study infectious pathogens.
green blue map of michigan
Health Lab
How does exposure to ‘forever chemicals’ impact your cancer risk
Pearce, professor of epidemiology at the School of Public Health and co-lead of Rogel’s cancer control and population sciences program, reflects on the project and why bringing this study to Michigan is so critical.
person holding walker with nurse next to them closer up on hands lower body
Health Lab
Long COVID happens in nursing homes, too
Post-acute sequelae of Sars-COV2 (PASC, long COVID) caused a decrease in independence and cognitive ability after coronavirus infection in nursing home residents
expert at stand hearing in suit
Health Lab
Keep telehealth alive and well, experts tell Senate subcommittee
Telehealth coverage by Medicare is scheduled to expire at the end of 2024; experts told Senators what they think should happen to preserve it.
physician talking to patient with lab researcher in background
Health Lab
Older adults left out of clinical research trials
Including older adults in research can be beneficial, explains a Michigan Medicine research, who says more should, and can be, done to have their insights.