Keywords: Spontaneous bacterial peritonitis; Procalcitonin; Liver cirrhosis; Ascites; Bacterial infection
Procalcitonin (PCT), a 116-amino acid prohormone of calcitonin, is normally synthesized in the C cells of the thyroid gland, and the current reference value (cut-off value) is estimated to be approximately 0.5 ng/mL in healthy populations [11-13]. Moreover, production of PCT occurs in various organs including the liver, lung, and kidneys during other medical conditions [14]. PCT is a well-known acute phase reactant protein as well as a C - reactive protein (CRP) [15]. PCT release during infection may be induced directly by microbial toxins and indirectly by humoral factors or a cell-mediated host response [13]. Bacterial endotoxins are the main stimulus for production of PCT and other cytokines such as Tumor Necrosis Factor (TNF)-α and Interleukin (IL)-6, which are involved in initiating acute phase responses in humans [12]. However, in liver insufficiencies such as LC, reduced catabolism of TNF-α and IL-6 is observed [12]. Therefore, compared with non-LC patients, TNF-α and IL-6 levels may be estimated to be less sensitive and specific in LC patients with bacterial infection [12]. High PCT levels were estimated to be a sensitive and specific marker for the initial diagnosis of bacterial infections [12,13,16]. Elevated serum PCT levels are more accurate indicators of bacterial infections than elevated CRP, TNF-α, or IL-6 levels [12,17], although these findings are controversial [18]. Viral infections, autoimmune disorders, allergic reactions, and local bacterial infections generally do not elevate PCT levels [13]. A recent review report and meta-analysis indicated that PCT is a helpful biomarker for early diagnosis of sepsis in critically ill patients, although it is not recommended for use as a single definitive test for diagnosing sepsis [19].
The value of using PCT levels for diagnosing infections such as SBP in LC patients has not been well established. Here we summarize the present data regarding PCT levels in the serum and ascites of patients with LC complicated by bacterial infections such as SBP.
Cultures of ascitic fluid are positive in 35%–65% of patients with SBP [20]. However, standard culture techniques fail to grow bacteria in up to 65% of neutrocytic ascites samples [24]. The positivity of ascites cultures has been reported to increase when the fluid is placed directly into blood culture flasks at the bedside, immediately after collection [20,24]. The usefulness of ascites pH, lactate and lactoferrin levels for the diagnosis of SBP has not been confirmed [20]. The possible usefulness of ascites Macrophage Inflammatory Protein type 1 beta (MIP-1β) levels for diagnosis of SBP was recently reported [26]. However, there is little evidence supporting MIP-1β use as a marker at present [6,26].
Of the three reports that investigated ascitic fluid PCT levels [16,26,28], two indicated no significant differences in PCT levels between patients with SBP and those with sterile ascites. However, two of these studies included only 10 SBP cases, limiting the relevance of their findings [26,28]. The remaining study reported that ascitic fluid PCT levels in SBP were significantly higher than those in sterile ascites but that ascitic fluid PCT levels were less accurate than IL-6 levels for the diagnosis of SBP [16].
Authors [Reference] |
SBP (n) |
Sterile ascites (n) |
p-value |
Viallon et al. [16] |
10.10 (2.6 – 24.0)* (n = 21) |
0.09 (0.0 – 0.23)* (n = 40) |
0.0001 |
Spahr et al. [28] |
0.74 ± 0.6 (0.1 – 1.72)** (n = 10) |
0.2 ± 0.1 (0.14 – 0.46)** (n = 10) |
< 0.05 |
Cekin et al. [27] |
1.01 (0.04 – 36.4)* (n = 59) |
0.3 (0.1 – 3.7)* (n = 24) |
< 0.001 |
Yuan et al. [29] |
0.62 (0.52 – 0.81)* (n = 42) |
0.28 (0.16 – 0.46)* (n = 42) |
< 0.0001 |
Lesińska et al. [26] |
1.08 ± 1.34 (? – ?)** (n = 10) |
0.44 ± 0.44 (? – ?)** (n = 22 ) |
0.51 |
Wu et al. [30] |
0.73 (? – ?)* (n = 111?) |
0.15 (? – ?)* (n = 40?) |
< 0.001 |
Authors [Reference] |
SBP (n) |
Sterile ascites (n) |
p-value |
Viallon et al. [16] |
1.30 (0.7 – 2.5)* (n = 21) |
0.08 (0.0 – 0.20)* (n = 40) |
0.0001 |
Spahr et al. [28] |
0.56 ± 0.6 (0.11 – 2)** (n = 10) |
0.18 ± 0.1 (0.12 – 0.39)** (n = 10) |
≥ 0.05 |
Lesińska et al. [26] |
1.30 ± 2.60 (? – ?)** (n = 10) |
0.38 ± 0.38 (? – ?)** (n = 22) |
0.48 |
Authors [Reference] |
AUC (%) |
Cutoff value (ng/mL) |
Sensitivity (%) |
Specificity (%) |
PPV (%) |
NPV (%) |
Viallon et al. [16] |
98
|
0.76 |
95 |
98
|
95 |
98 |
Connert et al. [12] |
? |
0.615
|
94.7 |
70.4
|
? |
? |
Cekin et al. [27] |
98.1 |
0.61
|
100 |
92 |
? |
? |
Yuan et al. [29] |
89
|
0.48
|
95 |
79 |
? |
? |
Lesińska et al. [26] |
58 |
?
|
30 |
?
|
? |
? |
Wu et al. [30] |
95 |
0.462
|
83.7 |
94.9
|
? |
? |
Authors [Reference] |
AUC (%) |
Cutoff value (ng/mL) |
Sensitivity (%) |
Specificity (%) |
PPV (%) |
NPV (%) |
Viallon et al. [16] |
96
|
0.30 |
95 |
85
|
77 |
97 |
Lesińska et al. [26] |
58 |
? |
20 |
?
|
? |
? |
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