Defense Date

2012

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Health Related Sciences

First Advisor

William Korzun

Abstract

Infections in patients with acute liver failure (ALF) and acute liver injury (ALI) are a frequent occurrence. Because ALF and ALI patients share many of the same clinical features as patients with severe sepsis and septic shock, identifying an infection based upon clinical manifestations is extremely difficult. Bacterial culture and sensitivity reports require 24 to 72 hours to be finalized after the need for a culture is suspected and obtained. During this time period, ALF and ALI patients are either not receiving required antibiotic therapy, receiving antibiotic therapy that is not required or not appropriate for the infecting bacterial pathogen, or receiving the correct antibiotic prophylaxis. Receiving an antibiotic that is not needed or inappropriate adds another level of complexity to the ALF and ALI patients because antibiotics may exacerbate liver dysfunction. The purpose of this study was to determine the utility of serum procalcitonin concentrations (SPCTC) as a biomarker of bacterial infections in patients with acute liver failure (ALF) and acute liver injury (ALI). This three part study measured SPCTC retrospectively on samples from ALF and ALI patients who were prospectively enrolled in the United States Acute Liver Failure Study Group (USALFSG) ALF and ALI studies. In the first part of the study, subjects were categorized according to how many SIRS continuum components they had and whether there was a documented infection. In the second part, serial samples on subjects who developed infections were identified. And, in the third part, serial samples on subjects diagnosed with infection on day one of the study and categorized based upon transplant free survival (TFS) or death and/or liver transplant (DoT) were identified. Procalcitonin was not found to be useful in identifying infection in the ALF and ALI patient populations. A cut-off for indication of infection was calculated to be 1.62 ng/mL using receiver operator curve (ROC) analysis. Despite the fact that there was an overall increase in SPCTC as the severity of illness increased in patients with a documented infection, there were confounding variables including antibiotic use, missing data, and small sample size that may have contributed to the poor sensitivity and specificity (0.643 and 0.620 respectively) calculated as part of the ROC analysis. SPCTC values appeared to be increased in subject with acetaminophen (APAP) toxicity and may have affected the cut-off, sensitivity, and specificity results. Increased SPCTC values were seen in APAP subjects who did not have a documented infection. It is unknown at this time if the SPCTC were increase due to liver damage, an undiagnosed infection, or as a result of increase cytokine production due to the APAP toxicity. Serial PCT concentrations in patients who achieved TFS showed a greater decrease over time than those of patients who died or received a liver transplant, however, the TFS group contained a large portion of APAP subjects. Further prospective studies are needed to determine the extent of interference with SPCTC in patients with APAP toxicity and to better define the PCT concentration cut-off between infection and no infection in the ALF and ALI populations.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

May 2012

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