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

Abstract

BackgroundBecause 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.MethodRetrospective 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.ResultsProcalcitonin 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/ConclusionsWhile 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.

C-Reactive Protein and Procalcitonin in Case Reports of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome

“…A limited number of paired PCT and other laboratory marker measurements could be assessed for correlation (Table 5). PCT correlated with liver function test measurements (most strongly with γ-glutamyl transpeptidase), indicating that PCT in DRESS may be an indicator of hepatic tissue damage as found by other investigators [73]. There was no correlation between PCT and eosinophil count (21 paired observations), suggesting that the pathomechanisms of PCT elevation and eosinophilia in DRESS syndrome are independent of each other.…”

“…Indeed, PCT elevation has been observed in cases of liver injury independent of the presence of bacterial infection. Rule et al [73] found a median PCT value of > 1.57 ng/mL in 59 patients with acute liver failure without sepsis. There was also no significant difference in PCT values between the 56 patients with and the 59 patients without bacterial infection.…”

Procalcitonin concentrations as a predictor of unexpected readmission and mortality after intensive care unit discharge: A retrospective cohort study

“…[24] A recent study looking at PCT concentrations in acute liver failure patients also found poor correlation between sepsis and PCT levels in this type of patients, presumably due to presence of extensive inflammation. [25] Regardless, our study attempted to study all ICU patients rather than a specific cohort.…”

Hepatic Macrophages are the Cell Source of Hepatic Procalcitonin in Acute Liver Failure

“…In our study, hepatic macrophages but not hepatocytes were found to be the cell source of hepatic PCT upregulation in ALF. Moreover, previous studies have shown that serum PCT is elevated in patients with ALF and ACLF [10,27,28], and the liver is one of the main sources of elevated serum PCT [7,29,30] in sepsis and cytokine storms. Thus, further study is required to clarify the involvement of hepatic PCT-especially that expressed by hepatic macrophages-in the elevation of serum PCT.…”