Sepsis in liver failure patients: Diagnostic challenges and recent advancements

Table 3 Summary of the performance, advantages, and limitations of various traditional and novel biomarkers of sepsis

Biomarkers	Overall performance for sepsis	Advantages	Limitations
CRP	Pooled sensitivity 80% and pooled specificity 61% for BI in general[49]	Wide availability. Low cost	Low specificity for BI. Falsely low levels in liver failure. Lag time: 12-24 hours. False positive in inflammation
PCT	Pooled sensitivity 77% and pooled specificity of 79% in general[53]	Easily available. Validated across multiple studies. Rapid elevation, 3–4 hours after BI	Modest to poor discriminatory role in liver failure patients. Varying cut-off levels. False positive in inflammation. Poor performance in renal failure and immunocompromised patients
IL-6	Pooled sensitivity 85% and specificity 91% for BI in cirrhosis[58]	Estimation is accurate, fast, and simple	It is a non-specific pro-inflammatory cytokine. Needs further studies in liver failure patients
HDL-C	HDL-C has an inverse correlation with BI[65,66]	Simple test. Low-cost. Widely available	Inverse correlation also exists between HDL-C and liver disease per se. Needs further studies as a biomarker for sepsis
Presepsin	Overall diagnostic sensitivity 83% and specificity 78%[59]	Better performance in liver failure patients than CRP and PCT[48]. Specific association with gram negative sepsis-Detectable within 2 hours of BI	Limited availability. Expensive test. More effective as an adjunct biomarker than when used alone. Requires further validation studies
sTREM-1	Pooled sensitivity 85% andspecificity 79% for differentiating sepsis from SIRS[61]	Early detection, < 2 hours after BI. Short half-life, making it useful for treatment response	Not routinely available. Varying cut-off levels. Requires further validation studies. Only modest performance when used alone
Bacterial DNA testing	Next-Generation Sequencing methodenables the identification of all bacteria in the blood and body fluid[70,71]	Quick and wide-ranging detection of bacteria	Not routinely available. Primer cross-reactivity with human DNA. Limited specificityand inconsistent results. DNA without a live pathogen compromises interpretation
sCD206	Significant association with infection (AUROC 71%) and mortality in ALF (AUROC 81%)[63]	It is among few novel biomarker evaluated in ALF patients	Not routinely available for use. Levels also increases in fungal and viral infection.Requires further validation studies

CRP: C-reactive protein; BI: Bacterial infection; PCT: Procalcitonin; IL: Interleukin; HDL: High density lipoprotein; sTREM-1: Soluble triggering receptor expressed on myeloid cell-1; SIRS: Systemic inflammatory response syndrome; AUROC: Area under receiver operating characteristics; ALF: Acute liver failure.