Procalcitonin Identifies Cell Injury, Not Bacterial Infection, in Acute Liver Failure

Abstract

Background: Because acute liver failure (ALF) patients share many clinical features with severe sepsis and septic shock, identifying bacterial infection clinically in ALF patients is challenging. Procalcitonin (PCT) has proven to be a useful marker in detecting bacterial infection. We sought to determine whether PCT discriminated between presence and absence of infection in patients with ALF.

Method: Retrospective analysis of data and samples of 115 ALF patients from the United States Acute Liver Failure Study Group randomly selected from 1863 patients were classified for disease severity and ALF etiology. Twenty uninfected chronic liver disease (CLD) subjects served as controls.

Results: Procalcitonin concentrations in most samples were elevated, with median values for all ALF groups near or above a 2.0 ng/mL cut-off that generally indicates severe sepsis. While PCT concentrations increased somewhat with apparent liver injury severity, there were no differences in PCT levels between the pre-defined severity groups-non-SIRS and SIRS groups with no documented infections and Severe Sepsis and Septic Shock groups with documented infections, (p = 0.169). PCT values from CLD patients differed from all ALF groups (median CLD PCT value 0.104 ng/mL, (p ≤0.001)). Subjects with acetaminophen (APAP) toxicity, many without evidence of infection, demonstrated median PCT >2.0 ng/mL, regardless of SIRS features, while some culture positive subjects had PCT values <2.0 ng/mL.

Summary/conclusions: While PCT appears to be a robust assay for detecting bacterial infection in the general population, there was poor discrimination between ALF patients with or without bacterial infection presumably because of the massive inflammation observed. Severe hepatocyte necrosis with inflammation results in elevated PCT levels, rendering this biomarker unreliable in the ALF setting.

Conflict of interest statement

Competing Interests: Siemens Healthcare Diagnostics provided instrumentation and reagents only for this study. The authors have no other relevant declarations relating to Siemens Healthcare Diagnostics. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Median PCT Values by Category.

This graph represents the median PCT values for the five patient severity groups. The lower dashed horizontal line represents the 0.1 ng/mL PCT cut-off value indicative of no infection. The upper dotted horizontal line represents the 2.0 ng/mL PCT cut-off value indicative of severe sepsis.

Fig 2. Receiver Operator Curve for the Detection of Infection in ALF and ALI patients Using PCT.

The ROC analysis resulted in an AUC of 0.697 with a sensitivity of 64.3% and a specificity of 62.0% for the use of PCT in the detection of infection this population of ALF patients.

Fig 3. Median APAP vs All Other Etiologies PCT values by Category.

This graph represents the median PCT values for the four ALF patient severity groups sorted by etiologies: APAP and All Others etiologies (combined viral and other) with the lower dashed line indicative of no infection (0.1 ng/mL) and the upper dotted line indicative of severe sepsis (2.0 ng/mL).