New Biomarker of Liver Dysfunction During Sepsis Identified

Columbus, Ohio

7/14/2006

Detection of high levels of a protein in the blood stream during severe infection has been found by critical care researchers at the Ohio State University Medical Center to be a marker of ongoing damage and metabolic derangement in the liver. The research provides new insights into the mechanisms of sepsis-induced organ failure, which is the leading cause of death in medical intensive care units.

The findings, recently published in the journal Critical Care Medicine, indicate that changes in vital organ function are explained by events at the mitochondrial level. Mitochondria are the primary source of cell energy.

The study is the first to show how mitochondrial populations acutely change during sepsis, with damaged mitochondria being removed by the cell’s normal clearance mechanism in the early phase of life-threatening sepsis and later being replaced during recovery from sepsis. Sepsis is an illness caused by overwhelming infection of the blood or tissues by toxin-producing organisms.

“The research sheds light on the mechanism by which the function of vital organs, such as the liver, becomes compromised during sepsis. We observed an inverse relationship between blood levels of the liver mithochondrial enzyme, carbamoyl phosphate sythetase-1 (CPS-1), with mitochondrial respiratory capacity in the liver. This was demonstrated in the subacute stages of sepsis,” said Dr. Elliott Crouser, a pulmonologist and critical care researcher at OSU Medical Center and lead author of the study.

In addition, the ordering of liver mitochondrial damage and repair relative to the release of CPS-1 into the circulation implies that damaged mitochondria are selectively removed from the liver during sepsis and are subsequently replaced, according to Crouser.

“Restoration of mitochondrial populations in the liver and reduced levels of CPS-1 appears to signal recovery from sepsis,” says Crouser.

The study’s authors concluded that CPS-1 is a novel marker of organ injury, reflecting functionally significant mitochondrial damage and accelerated liver mitochondrial turnover in the context of sepsis. Furthermore, the research provides evidence that CPS-1 may be superior to conventional markers of liver damage during sepsis.

“Although we have found that circulating CPS-1 is a marker of mitochondrial damage and depletion in the liver during the subacute phase of CLP sepsis, further research is needed to determine the clinical utility of CPS-1 as a marker of sepsis severity,” Crouser said.

Along with Crouser, other Ohio State researchers involved in the study were Dr. Charles Cook, Jennifer Huff and Mark Julian.

The National Institutes of Health supported this research.