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ORIGINAL ARTICLE
Year : 2022  |  Volume : 35  |  Issue : 2  |  Page : 548-552

Diagnostic role of procalcitonin serum level in hepatitis C virus-infected patients with spontaneous bacterial peritonitis


1 Department of Internal Medicine, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
2 Department of Clinical and Chemical Pathology, Faculty of Medicine, Alexandria, Egypt

Date of Submission21-Nov-2020
Date of Decision22-Dec-2020
Date of Acceptance01-Feb-2021
Date of Web Publication27-Jul-2022

Correspondence Address:
Mohammed S. S. Shater
Department of Internal Medicine, Faculty of Medicine, University of Alexandria Champollion Street, El-Khartoum Square, Azarita Medical Campus, Alexandria 21521
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_430_20

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  Abstract 


Objective
We aimed at the evaluation of the role of quantification of serum procalcitonin (PCT) in the detection of spontaneous bacterial peritonitis (SBP) in hepatitis C-related cirrhosis before and after initiation of antibiotic therapy.
Background
SBP is a lethal consequence of advanced cirrhosis. The outcome is heavily affected by early detection and treatment. PCT has been evaluated during acute bacterial infections and sepsis.
Patients and methods
We included 60 patients with ascites due to hepatitis C-related cirrhosis, who were divided in two groups: group 1 included 40 naïve patients with SBP, and group 2 included 20 patients with sterile ascites as a control. After history taking and clinical examination, full blood count, liver test profile, and renal functions were done. Moreover, C-reactive protein and erythrocyte sedimentation rate levels were measured. Serum PCT was measured by immunoassay. Diagnostic ascitic sample analysis was done for the polymorphonuclear leukocyte (PMNL) count, albumin levels, and ascetic fluid culture.
Results
Serum PCT was significantly elevated in group 1 before treatment than after treatment, as well as when compared with group 2. There was no statistically significant correlation between the change in the C-reactive protein level and that of the serum PCT before and after treatment in group 1. There is no significant correlation between increases in the serum PCT and the results of bacterial growth of ascetic fluid culture group before and after treatment.
Conclusion
PCT levels in the serum appear to provide a good diagnostic certainty in the diagnosis of SBP in cirrhotic patients at a cutoff value of 0.17 ng/ml for patients with either culture-positive or negative SBP.

Keywords: liver cirrhosis, procalcitonin, sepsis, spontaneous bacterial peritonitis


How to cite this article:
El Hasafy MY, El Kaffash DM, Shater MS, Attia NA. Diagnostic role of procalcitonin serum level in hepatitis C virus-infected patients with spontaneous bacterial peritonitis. Menoufia Med J 2022;35:548-52

How to cite this URL:
El Hasafy MY, El Kaffash DM, Shater MS, Attia NA. Diagnostic role of procalcitonin serum level in hepatitis C virus-infected patients with spontaneous bacterial peritonitis. Menoufia Med J [serial online] 2022 [cited 2024 Mar 29];35:548-52. Available from: http://www.mmj.eg.net/text.asp?2022/35/2/548/352202




  Introduction Top


In end-stage liver disease, bacterial translocation leads to increased infection susceptibility, especially spontaneous bacterial peritonitis (SBP), with the release of the inflammatory cytokine, contributing to hemodynamic dysfunction. This in turn has a survival effect even following the cure of infection [1–3]. SBP is the ascitic fluid infection without visceral perforation or intra-abdominal localizing infection [4–6].

Procalcitonin (PCT) structurally is a 116-amino acid with ~25–30 h half-life[7]. PCT is synthesized in different extra-thyroid neuroendocrine tissues during bacterial infection. Unlike other inflammatory cytokines, PCT concentrations are not raised after noninfectious/nonbacterial inflammations, and its degradation is not affected by liver cell failure, so it can discriminate between bacterial/nonbacterial etiologies of systemic inflammation [8–11].

Results on the validity and certainty of PCT in the early diagnosis of bacterial infection in patients with liver cirrhosis, especially SBP, are controversial, so we investigated the role of using PCT as a diagnostic marker for SBP in patients with hepatitis C virus (HCV)-related cirrhosis.


  Patients and methods Top


Our study design was a case–control study. The research was performed on 60 adult patients with HCV-related ascitic cirrhosis who were assigned into two different groups: group 1 included 40 patients with clinical symptoms of SBP, and group 2 included 20 age-matched and sex-matched patients with sterile ascetics as a control group. Patients were recruited from tertiary care university hospitals during the period from June to September 2018. Informed consent was obtained from every patient involved in the study. The study has been accepted in our institute by the local ethics committee.

The inclusion criteria were HCV-infected patients who presented with cirrhotic ascites. Cirrhotic ascites was diagnosed by shifting dullness with signs of chronic liver disease (palmar erythema, white nail, spider nevi, etc.) and by ultrasound (coarse liver, attenuated hepatic veins, dilated portal vein, etc.). SBP was diagnosed based on clinical manifestations (temperature >37.8°C or hypothermia, abdominal pain, tenderness, paralytic ileus, hypotension, and/or prehepatic coma in the form of slurred speech, asterixis, etc.) and bacteriological culture of ascetic fluid with identification of the causative organism and/or ascetic fluid polymorphs more than 250 cell/mm3. Age and sex-matched cases with sterile ascites were used as a control group. Patients with noncirrhotic ascites, patients with secondary bacterial peritonitis, patients with ascites owing to malignancy, and patients who received antibiotics 10 days before/or during the enrollment were excluded. Moreover, patients with thyroid disease, hepatitis B infection, autoimmune or metabolic liver disease, transplant patients, evident source of nonabdominal infections, and patients with malignancy were excluded.

All patients were subjected to a thorough history taking and a complete clinical examination. Laboratory parameters at admission included complete blood count, liver test profile, and renal function tests. Moreover, C-reactive protein (CRP), and erythrocyte sedimentation rate levels were measured. Serum PCT was measured by immunoassay[12]. Radiographic evaluation using ultrasound examinations of the abdomen and chest radiograph was done. At the time of admission, all patients had a diagnostic ascitic fluid sample analysis for the PMNL count, albumin levels, and ascetic fluid culture. The detection of ascetic fluid infection was based on the presence of white blood cell counts/PMNL in the ascetic fluid, and SBP culture positivity was confirmed if white blood cell counts exceed 500/mm3 and PMNL exceeded 250/mm3 correspondingly[13]. For the group of SBP, PCT was measured before receiving antibiotic therapy in the first 4 h of admission and after receiving the treatment in the form of two grams cefotaxime every 8 h or 2 g ceftriaxone once daily for 5–7 days.

Statistical analysis

Statistical analysis was done using IBM SPSS software package, version 26.0 (IBM Corp., Armonk, New York, USA). Qualitative data were described using a number (%), whereas quantitative data were described as mean ± SD. The normality of data distribution was assessed by the Kolmogorov–Smirnov test. A χ2 test and Fisher's exact test were used for categorical variables as appropriate. Student t test, Wilcoxon signed ranks test, or Mann–Whitney test was used for comparison between cases and control as appropriate. The sensitivity and specificity of serum PCT for exclusion/confirmation of SBP were assessed by plotting a receiver-operating characteristic curve. Statistical significance was assessed at P value less than 0.05. All calculated P values were two tailed.


  Results Top


The baseline characteristics of the study population are shown in [Table 1]. Group 1 included nine (22.5%) women and 31 (77.5%) were men. The age of the patients ranged between 39 and 74 years, and the mean age was 55.95 ± 8.30 years. In group 2, there were three (15%) women and 17 (85%) men. The age ranged between 44 and 70 years, with a mean of 55.40 ± 7.06 years.
Table 1: The demographic and clinical data of the studied groups

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Regarding serum CRP, it ranged between 0.90 and 129.0, with a mean of 36.81 ± 31.9, in group 1 before treatment, and ranged from 2.0 to 24.0, with the mean of 7.23 ± 6.17, in group 1 after treatment, whereas it ranged 2.0–7.0, with a mean of 4.70 ± 1.81, in group 2 (control), with a statistically significant difference between group 1 before and after the treatment (P1 < 0.001), a statistically significant difference between group 1 before treatment and the control (P2 < 0.001), and no statistically significant difference between group 1 after treatment and the control (P3 = 0.350). In the SBP group (group 1 before treatment), the cutoff value for serum CRP was more than 7 to exclude the diagnosis of bacterial infection, with sensitivity of 75%, specificity of 100%, and area under the curve was 0.799, with the 95% confidence interval = 0.680–0.917 (P < 0.001) [Table 2].
Table 2: Comparison between the studied groups according to serum C-reactive protein, serum procalcitonin, urine analysis results, and culture results

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Serum PCT ranged between 0.11 and 2.1, with a mean of 0.85 ± 0.82, in group 1 before treatment, 0.05–0.40, with a mean of 0.15 ± 0.11 in group 1 after treatment, whereas it ranged from 0.02 to 0.17, with a mean of 0.10 ± 0.06, in group 2 (control). There was a statistically significant difference between group 1 before and following the treatment (P1 < 0.001), a statistically significant difference between group 1 before treatment and the control (P2 < 0.001), and no statistically significant difference between group 1 after treatment and the control (P3 = 0.137). In SBP group (group 1 before treatment) [Table 2], we found no significant correlation between serum PCT and serum CRP neither before nor after treatment of SBP (P > 0.05). Similarly, we found no significant correlation between the serum levels of PCT and the culture results (P > 0.05).

The cutoff value for the serum PCT to confidently exclude bacterial infection was more than 0.17, with sensitivity of 85.0%, specificity of 100%, and area under the receiver-operating characteristic curve of 0.919, with the 95% confidence interval = 0.851–0.988 (P < 0.001) [Figure 1].
Figure 1: The ROC curve with sensitivity and specificity for different parameters for the diagnosis of HCV cirrhotic patients with spontaneous bacterial peritonitis before treatment (vs. control). AUC, area under the curve; CI, confidence interval; HCV, hepatitis C virus; NPV, negative predictive value; PPV, positive predictive value; ROC, receiver-operating characteristic. *Statistically significant at P value less than or equal to 0.05.

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  Discussion Top


The target of our study was to validate the diagnostic efficacy of the serum PCT level in the detection of SBP in HCV-infected cirrhotic patients. The study groups were age and sex matched. In the current study, bedside blood culture bottles were used to cultivate ascitic fluids, and the positive culture (Escherichia coli) was identified in eight (20%) patients. The increased culture-negative incidence of SBP among our cases can be interpreted by the bacterial opsonization occurring in ascitic fluid or the circulation making the bacteria noncultivatable in cultures[14].

The overrepresentation of gram negative microbes, like those mentioned by previous reports[14],[15], which showed that the Enterobacteriaceae family has gram-negative bacilli, especially E. coli, the commonest species that cause SBP, account for 60% of cases. This can be justified by the presence of the species that cause infection in the ascitic fluid in the gut. Lee et al.[16] reported serum CRP as a useful tool in diagnosing and treating patients with different inflammation conditions. It was also detected in 72% of patients who have cirrhosis complicated with bacterial infections, gut bleeding, massive ascites, or hepatic encephalopathy.

Our analysis showed that CRP levels in the sera of patients with SBP were more elevated than those in sterile ascites. Owing to an improved capillary permeability in the SBP category and peritonitis carcinomatosis, levels of CRP could be elevated in ascitic fluid. CRP's half-life in actively contaminated cases will increase to 18 h. Additionally, CRP resolution in the ascitic fluid was unknown[17]. Unlike CRP, PCT synthesis was documented as high in reaction to bacterial infection rather than noninfectious/nonbacterial inflammations[18].

Koulaouzidis et al.[19] found that PCT (at a level of 0.75 ng/ml) has 95% sensitivity and 98% specificity to distinguish between sterile ascites and SBP. Muller et al.[20] also demonstrated that PCT could differentiate community-acquired pneumonia from other respiratory diseases with a sensitivity and specificity of 74 and 85%, respectively. Serum PCT between 0.1 and 0.25 ng/ml could diagnose bacterial infection in two randomized trials[21],[22]. PCT values were a more effective marker for bacterial infections than levels of CRP, both in differentiating bacterial from noninfectious inflammation and in distinguishing between bacterial/viral infections[23].

Our data showed a significantly raised PCT in cirrhotic patients with infected ascites than those with sterile ascites. The current study showed that at a cutoff value more than 0.17 ng/ml, PCT could rule in/out bacterial ascitic infection with higher sensitivity/specificity compared with CRP. Viallon et al.[11] proved that PCT was the strongest marker for the detection of SBP, with a cutoff level of 0.75 ng/ml with high sensitivity/specificity.

Tang et al.[24] reported that PCT has a lower diagnostic performance in discriminating sepsis from systemic inflammation. Some cytokines can attenuate the induction of PCT, such as interferon-α which is secreted in virus-related infection[25]. Despite that, other studies reported that the serum PCT was not a beneficial marker for predicting SBP (30% sensitivity)[26],[27].

The current study shows no significant correlation between the increasing level of PCT and CRP as a marker of bacterial infection. Moreover, there was an insignificant correlation between the increasing level of serum PCT as a marker of bacterial infection and the culture of bacterial growth results. As the clinical discretion does not exclude SBP, the analysis of a diagnostic sample of the ascitic fluid is mandatory in all patients with liver cirrhosis presented with ascites in the following conditions: at hospital admission, in cases of variceal bleeding, abdominal pain, presence of inflammatory manifestations, unexplained deterioration of liver or renal function, and hepatic encephalopathies[28].


  Conclusion Top


In conclusion, the key point for decreasing the mortality in liver cirrhosis patients presented with ascitic fluid infection is the rapid diagnosis. In this regard, and based on ease of utility, rapidity, and low-cost features, the determination of serum PCT seems to have a promising important value in the fast diagnosis and detection of cirrhosis-related infections, especially SBP, with a view to timely initiation of appropriate treatment that may aid to enhance the overall survival of cirrhotic patients at increased risk of SBP; however, we do not recommend to replace ascitic fluid examination.


  Acknowledgements Top


Contributions list: Mohamed Y. El Hasafy: conceptualization, methodology, and revision of the manuscript. Dalal M. El Kaffash: methodology, biochemical analysis, revised manuscript, and results. Mohammed S.S. Shater: patient and data collection, writing manuscript, revising data analysis, and revising final version. Nehal A. El-Salam Attia: patient and data collection, writing manuscript, revising data analysis, and revising final version.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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