Ascitic Fluid Calprotectin as an Accurate Diagnostic Marker for Spontaneous Bacterial Peritonitis

Spontaneous bacterial peritonitis (SBP) is an infection of the ascitic fluid in patients with liver cirrhosis and portal hypertension. There is no obvious surgical cause as perforation or intraabdominal inflammatory focus as abscess. Up to 30% of the ascitic patients will develop SBP.

SBP is attributed to immune dysfunction, bacterial translocation, circulatory dysfunction and inflammatory status. SBP is diagnosed by ascitic fluid analysis . SBP was defined as polymorphonuclear leucocyte count (PMN) >250/mm3 in ascitic fluid, . Not all cases are associated with positive ascitic fluid cultures.

There are variants of ascitic fluid infections as culture-negative neutrocytic ascites, monomicrobial non-neutrocytic bacterascites, polymicrobial bacterascites and secondary bacterial peritonitis.

The advent of the SBP carries a poor prognosis where the hospital mortality ranged from 10 to 50%. As a consequence, any patient with SBP should be assessed for liver transplantation. Immediate treatment with antibiotics and IV albumin should be initiated.

Studies were conducted on alternatives of the ascitic PMN count as high sensitivity C-reactive protein (hsCRP), serum procalcitonin, urinary lipocalin, ascitic lactoferrin, homocysteine and fecal or ascitic calprotectin.

The gold standard test for SBP is ascitic fluid analysis with measurement of the PMN. It is useful for the diagnosis and monitoring of treatment. The culture of the ascitic fluid may be positive if was done correctly .

There is a variant of SBP that is called culture-negative neutrocytic ascites. It is characterized by elevated ascitic fluid PMN but the culture is negative. It is managed exactly as classic SBP. Such cases would be missed if cultures were not done The manual PMN counting is time consuming, laborious and required some experience to avoid intra- and inter-observer variability. So, a simple rapid bedside test would be useful clinically.

Calprotectin is acute-phase inflammatory protein that is released from the PMN. Calprotectin has anti-proliferative and antimicrobial properties. Calprotectin is used clinically widespread in the diagnosis and monitoring treatment of inflammatory bowel disease .

Study Overview

• Status: Recruiting
• Conditions: Spontaneous Bacterial Peritonitis
• Intervention / Treatment: Diagnostic test: ascitic fluid calprotectin

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alaa S Mohamed, resident; Phone Number: 01159603636; Email: alaasabr@med.sohag.edu.eg
• Study Contact Backup: Name: laila M Yousef, professor

Study Locations

• Egypt
  • Sohag, Egypt
    • Recruiting
    • Sohag University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

-

The patients were divided into two groups:

1. Non-SBP group: it included 25 patients with cirrhotic ascites without clinical or laboratory evidence of SBP.
2. SBP group: it included 25 patients with cirrhotic ascites with SBP. They were diagnosed by positive ascitic fluid bacterial culture, an increase in PMNLs count in ascites (>250 cells/mm3) and without any intra-abdominal source of infection.

Exclusion Criteria:

• (1) Cirrhotic patients with and without SBP receiving antibiotics in last 1 week.

  (2) Recent abdominal surgery (<3 months). (3) abdominal malignancy [hepatocellular carcinoma (HCC), colorectal carcinoma, gastric carcinoma, pancreatic carcinoma, cholangiocarcinoma].

  (4) Intra-abdominal infected lesions, such as abscess, appendicitis, cholecystitis, and pancreatitis.

  (5) History of inflammatory bowel disease (Crohn's disease, ulcerative colitis).

  (6) patients with heart failure (HF), hematological, and autoimmune disorders were excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: case; people who have spontaneous bacterial peritonitis	Diagnostic test: ascitic fluid calprotectin; ascitic fluid calprotectin
ACTIVE_COMPARATOR: control; people who donot have spontaneous bacterial peritonitis	Diagnostic test: ascitic fluid calprotectin; ascitic fluid calprotectin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-CBC	WBCs count and differential,RBCs count,HB,mcv,Mch,Mchc,platelete count	6 months
2-liver function test	AlT,ASt,Albumin,total protein,bilirubin	6 months
3-Renal function test	serum create and urea	6 months
4-Ascitic fluid analysis(physical,chemical,microscopic)	physical(colour,aspect) chemical(protien,glucose) microscopical(wbcs total and differential,Rbcs),bacterial culture	6 months
Ascitic Fluid calprotectin	ascitic fluid calprotectin by ELISA	6 months
INR	international normalization time	6 months

Collaborators and Investigators

• Sponsor: Sohag University

Publications and helpful links

General Publications

• European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol. 2010 Sep;53(3):397-417. doi: 10.1016/j.jhep.2010.05.004. Epub 2010 Jun 1. No abstract available.
• Xiol X, Castellvi JM, Guardiola J, Sese E, Castellote J, Perello A, Cervantes X, Iborra MJ. Spontaneous bacterial empyema in cirrhotic patients: a prospective study. Hepatology. 1996 Apr;23(4):719-23. doi: 10.1002/hep.510230410.
• Bernardi M. Spontaneous bacterial peritonitis: from pathophysiology to prevention. Intern Emerg Med. 2010 Oct;5 Suppl 1:S37-44. doi: 10.1007/s11739-010-0446-x.
• Marciano S, Diaz JM, Dirchwolf M, Gadano A. Spontaneous bacterial peritonitis in patients with cirrhosis: incidence, outcomes, and treatment strategies. Hepat Med. 2019 Jan 14;11:13-22. doi: 10.2147/HMER.S164250. eCollection 2019.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 10, 2022
• Primary Completion (ANTICIPATED): December 1, 2022
• Study Completion (ANTICIPATED): December 1, 2022

Study Registration Dates

• First Submitted: June 14, 2022
• First Submitted That Met QC Criteria: June 14, 2022
• First Posted (ACTUAL): June 16, 2022

Study Record Updates

• Last Update Posted (ACTUAL): August 12, 2022
• Last Update Submitted That Met QC Criteria: August 10, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Peritoneal Diseases; Intraabdominal Infections; Peritonitis
• Other Study ID Numbers: Soh-Med-22-06-07

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No