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El Raziky M, Rashwan M, Tamim HH, Afify S, Lithy RM. Role of IL-6, TNF-α and VCAM-1 as predictors of renal impairment in patients with spontaneous bacterial peritonitis. Trans R Soc Trop Med Hyg 2025; 119:524-533. [PMID: 39758003 DOI: 10.1093/trstmh/trae139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Revised: 10/17/2024] [Accepted: 12/18/2024] [Indexed: 01/07/2025] Open
Abstract
BACKGROUND Multiple mechanisms may contribute to the occurrence of renal impairment (RI) in patients with spontaneous bacterial peritonitis (SBP). One such mechanism is systemic inflammatory response syndrome, which involves the release of pro-inflammatory cytokines (tumour necrosis factor [TNF]-α, interleukin [IL]-6 and vascular cell adhesion molecule [VCAM]-1). The goal of this research was to evaluate the role of IL-6, TNF-α and VCAM-1 as potential predictors of RI and mortality in cirrhotic patients with SBP. METHODS This study included 90 cirrhotic patients with SBP, divided into two equal groups: group A was patients without RI and group B was patients with RI. Based on mortality outcomes, the patients were further categorized into group 1 (recovery, n=70) and group 2 (death, n=20). TNF-α, IL-6 and VCAM-1 serum levels were measured using enzyme-linked immunosorbent assay. RESULTS RI occurred in 50% (45/90) of the study population. Among the 90 patients, 10 (11.1%) had elevated IL-6 levels, 8 (8.9%) had elevated TNF-α levels and 6 (6.7%) had elevated VCAM-1 levels. There were no significant variations in cytokine levels between groups A and B. With an area under the curve of 0.5, the three cytokines showed comparable sensitivity and specificity as predictors of RI. CONCLUSIONS The use of TNF-α, IL-6 and VCAM-1 as predictive markers for RI and mortality in SBP patients is not recommended, as these biomarkers demonstrated limited diagnostic value.
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Affiliation(s)
- Maissa El Raziky
- Endemic Medicine and Hepato-Gastroenterology Department, Faculty of Medicine, Cairo University, Cairo 3753450, Egypt
| | - Mennatallah Rashwan
- Endemic Medicine and Hepato-Gastroenterology Department, Faculty of Medicine, Cairo University, Cairo 3753450, Egypt
| | - Hend Hamed Tamim
- Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo 3753450, Egypt
| | - Shimaa Afify
- Department of Gastroenterology, National Hepatology and Tropical Medicine Research Institute, Cairo 3753450, Egypt
| | - Rania M Lithy
- Endemic Medicine and Hepato-Gastroenterology Department, Faculty of Medicine, Cairo University, Cairo 3753450, Egypt
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Juncu S, Minea H, Lungu A, Jucan A, Avram R, Buzuleac AM, Cojocariu C, Diaconu LS, Stanciu C, Trifan A, Sîngeap AM. Fluoroquinolones for the Prophylaxis of Spontaneous Bacterial Peritonitis in Patients with Liver Cirrhosis: Are They Losing Ground? Life (Basel) 2025; 15:586. [PMID: 40283141 PMCID: PMC12028953 DOI: 10.3390/life15040586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Revised: 03/24/2025] [Accepted: 03/31/2025] [Indexed: 04/29/2025] Open
Abstract
Spontaneous bacterial peritonitis (SBP) is the most common bacterial infection in cirrhotic patients. Historically, the bacterial spectrum was dominated by Gram-negative bacteria. However, recent studies showed that fluoroquinolone (FQ)-based prophylaxis promotes the intestinal overgrowth of Gram-positive bacteria and contributes to the selection of quinolone-resistant Gram-negative bacteria, increasing multidrug-resistant (MDR) organism infections. FQ resistance rates reach up to nearly one-third in community-acquired cases and 50% in hospital-acquired cases, raising concerns about FQ efficacy. Moreover, rare but serious side effects further limit FQ use. Predictive factors of FQ treatment failure have been identified, guiding management strategies. Rifaximin has emerged as a promising alternative for SBP prophylaxis, with encouraging results. This review aims to explore the shifting role of FQ-based SBP prophylaxis, focusing on the emerging concerns, side effects, and alternative strategies. While norfloxacin remains a first-line prophylactic in cirrhotic patients with low ascitic protein levels, its efficacy appears to be reduced in those with advanced liver failure or additional risk factors for MDR organisms. In these subgroups, alternative prophylactics, such as trimethoprim-sulfamethoxazole or rifaximin, may be preferable. We propose a risk-stratification approach to guide treatment selection, with further studies needed to refine these criteria.
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Affiliation(s)
- Simona Juncu
- Department of Gastroenterology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Universitatii Street No. 16, 700115 Iasi, Romania; (S.J.); (A.L.); (A.J.); (R.A.); (A.-M.B.); (C.C.); (C.S.); (A.T.); (A.-M.S.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency County Hospital, Bd. Independentei No. 1, 700111 Iasi, Romania
| | - Horia Minea
- Department of Gastroenterology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Universitatii Street No. 16, 700115 Iasi, Romania; (S.J.); (A.L.); (A.J.); (R.A.); (A.-M.B.); (C.C.); (C.S.); (A.T.); (A.-M.S.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency County Hospital, Bd. Independentei No. 1, 700111 Iasi, Romania
| | - Andreea Lungu
- Department of Gastroenterology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Universitatii Street No. 16, 700115 Iasi, Romania; (S.J.); (A.L.); (A.J.); (R.A.); (A.-M.B.); (C.C.); (C.S.); (A.T.); (A.-M.S.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency County Hospital, Bd. Independentei No. 1, 700111 Iasi, Romania
| | - Alina Jucan
- Department of Gastroenterology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Universitatii Street No. 16, 700115 Iasi, Romania; (S.J.); (A.L.); (A.J.); (R.A.); (A.-M.B.); (C.C.); (C.S.); (A.T.); (A.-M.S.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency County Hospital, Bd. Independentei No. 1, 700111 Iasi, Romania
| | - Raluca Avram
- Department of Gastroenterology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Universitatii Street No. 16, 700115 Iasi, Romania; (S.J.); (A.L.); (A.J.); (R.A.); (A.-M.B.); (C.C.); (C.S.); (A.T.); (A.-M.S.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency County Hospital, Bd. Independentei No. 1, 700111 Iasi, Romania
| | - Ana-Maria Buzuleac
- Department of Gastroenterology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Universitatii Street No. 16, 700115 Iasi, Romania; (S.J.); (A.L.); (A.J.); (R.A.); (A.-M.B.); (C.C.); (C.S.); (A.T.); (A.-M.S.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency County Hospital, Bd. Independentei No. 1, 700111 Iasi, Romania
| | - Camelia Cojocariu
- Department of Gastroenterology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Universitatii Street No. 16, 700115 Iasi, Romania; (S.J.); (A.L.); (A.J.); (R.A.); (A.-M.B.); (C.C.); (C.S.); (A.T.); (A.-M.S.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency County Hospital, Bd. Independentei No. 1, 700111 Iasi, Romania
| | - Laura Sorina Diaconu
- Department of Internal Medicine and Gastroenterology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Internal Medicine and Gastroenterology, University Emergency Hospital, 050098 Bucharest, Romania
| | - Carol Stanciu
- Department of Gastroenterology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Universitatii Street No. 16, 700115 Iasi, Romania; (S.J.); (A.L.); (A.J.); (R.A.); (A.-M.B.); (C.C.); (C.S.); (A.T.); (A.-M.S.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency County Hospital, Bd. Independentei No. 1, 700111 Iasi, Romania
| | - Anca Trifan
- Department of Gastroenterology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Universitatii Street No. 16, 700115 Iasi, Romania; (S.J.); (A.L.); (A.J.); (R.A.); (A.-M.B.); (C.C.); (C.S.); (A.T.); (A.-M.S.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency County Hospital, Bd. Independentei No. 1, 700111 Iasi, Romania
| | - Ana-Maria Sîngeap
- Department of Gastroenterology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Universitatii Street No. 16, 700115 Iasi, Romania; (S.J.); (A.L.); (A.J.); (R.A.); (A.-M.B.); (C.C.); (C.S.); (A.T.); (A.-M.S.)
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Emergency County Hospital, Bd. Independentei No. 1, 700111 Iasi, Romania
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Wejnaruemarn S, Susantitaphong P, Komolmit P, Treeprasertsuk S, Thanapirom K. Procalcitonin and presepsin for detecting bacterial infection and spontaneous bacterial peritonitis in cirrhosis: A systematic review and meta-analysis. World J Gastroenterol 2025; 31:99506. [PMID: 39958447 PMCID: PMC11752710 DOI: 10.3748/wjg.v31.i6.99506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 11/23/2024] [Accepted: 12/23/2024] [Indexed: 01/10/2025] Open
Abstract
BACKGROUND Diagnosing bacterial infections (BI) in patients with cirrhosis can be challenging because of unclear symptoms, low diagnostic accuracy, and lengthy culture testing times. Various biomarkers have been studied, including serum procalcitonin (PCT) and presepsin. However, the diagnostic performance of these markers remains unclear, requiring further informative studies to ascertain their diagnostic value. AIM To evaluate the pooled diagnostic performance of PCT and presepsin in detecting BI among patients with cirrhosis. METHODS We performed a systematic search of the MEDLINE, EMBASE, and Scopus databases for studies that evaluated the diagnostic role of PCT and presepsin from inception to June 2024. Sensitivity and specificity values were pooled using a random effects model. BI was diagnosed based on clinical manifestations, physical examination, laboratory data, and radiological findings. RESULTS Of the 6639 articles retrieved, 28 met the inclusion criteria and included 4287 patients with 1789 cases of BI (41.7%). The bivariate pooled sensitivity and specificity estimates of PCT for BI diagnosis were 0.73 [95% confidence interval (CI): 0.64-0.81] and 0.83 (95%CI: 0.79-0.87), respectively. The diagnostic odds ratio (DOR) of PCT was 17.21 (95%CI: 9.57-30.95). Presepsin showed a pooled sensitivity of 0.75 (95%CI: 0.60-0.86), specificity of 0.80 (95%CI: 0.68-0.88), and DOR of 12.33 (95%CI: 5.10-29.83) for diagnosing BI. The pooled sensitivity and specificity of PCT for diagnosing spontaneous bacterial peritonitis (SBP) were 0.76 (95%CI: 0.67-0.84) and 0.87 (95%CI: 0.78-0.92), respectively. The positive likelihood ratio of PCT was 5.57 (95%CI: 3.34-9.29), which was sufficiently indicative of SBP. The DOR of PCT was 29.50 (95%CI: 12.30-70.80). CONCLUSION PCT and presepsin have high sensitivity and specificity for detecting BI in patients with cirrhosis. Furthermore, PCT has good diagnostic value as a rule-in test for SBP diagnosis.
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Affiliation(s)
- Salisa Wejnaruemarn
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - Paweena Susantitaphong
- Division of Nephrology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok 10330, Thailand
- Center of Excellence for Metabolic Bone Disease in CKD Patients, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Piyawat Komolmit
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
- Center of Excellence in Hepatic Fibrosis and Cirrhosis, Chulalongkorn University, Bangkok 10330, Thailand
- Excellence Center in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - Sombat Treeprasertsuk
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
| | - Kessarin Thanapirom
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
- Center of Excellence in Hepatic Fibrosis and Cirrhosis, Chulalongkorn University, Bangkok 10330, Thailand
- Excellence Center in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok 10330, Thailand
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Barreto CMDA, do Valle EA, Moreira JPDL, E Silva KF, Rosas SLB, Santana PT, Pittella AM, Pereira G, Fernandes FF, Perez RDM, de Souza HSP. Gut-related molecules as potential biomarkers in patients with decompensated cirrhosis. Ann Hepatol 2024; 30:101567. [PMID: 39276985 DOI: 10.1016/j.aohep.2024.101567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 07/06/2024] [Accepted: 07/18/2024] [Indexed: 09/17/2024]
Abstract
INTRODUCTION AND OBJECTIVES Microbial translocation contributes to cirrhosis progression and complications. This study aims to investigate whether molecules related to intestinal permeability or microbial translocation can serve as prognostic biomarkers in patients with decompensated cirrhosis. MATERIALS AND METHODS We prospectively evaluated hospitalized patients with decompensated cirrhosis for liver function, complications during hospitalization, in-hospital mortality, composite outcomes of in-hospital mortality and complications, 12-month mortality, and survival rates. Blood samples were collected upon admission, and 1,3 beta-d-glucan, zonulin, calprotectin, and lipopolysaccharide-binding protein were measured using commercial kits. RESULTS Ninety-one patients with decompensated cirrhosis were enrolled. The mean age was 58 ± 12 years; 57% were male. The three main cirrhosis etiologies were hepatitis C (35%), alcohol (25%), and non-alcoholic steatohepatitis (17%). In terms of liver function, 52% were Child C, and 68% had model for end-stage liver disease ≥15. The in-hospital and one-year mortality rates were 31% and 57%, respectively. Child-Pugh, 1,3 beta-glucan, and model for end-stage liver disease were positively correlated; zonulin was associated with complications during hospitalization (acute kidney injury) and composite outcomes, and calprotectin was associated with all outcomes except 12-month mortality. CONCLUSIONS Serum calprotectin and zonulin levels emerge as noninvasive prognostic biomarkers for potentially unfavorable outcomes in patients with decompensated cirrhosis.
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Affiliation(s)
- Camila Marques de Alcântara Barreto
- Department of Clinical Medicine, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-913, Brazil; Bonsucesso Federal Hospital, Rio de Janeiro, 20950-003, Brazil
| | - Eliane Almeida do Valle
- Department of Clinical Medicine, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-913, Brazil; Pedro Ernesto University Hospital, Rio de Janeiro, 20551-030, Brazil
| | | | - Katia Farias E Silva
- Department of Clinical Medicine, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-913, Brazil; Pedro Ernesto University Hospital, Rio de Janeiro, 20551-030, Brazil
| | - Siane Lopes Bittencourt Rosas
- Department of Clinical Medicine, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-913, Brazil
| | - Patrícia Teixeira Santana
- Department of Clinical Medicine, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-913, Brazil
| | | | - Gustavo Pereira
- Bonsucesso Federal Hospital, Rio de Janeiro, 20950-003, Brazil
| | | | - Renata de Mello Perez
- Department of Clinical Medicine, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-913, Brazil; D'Or Institute for Research and Education (IDOR), Botafogo, Rio de Janeiro, 22281-100, Brazil
| | - Heitor Siffert Pereira de Souza
- Department of Clinical Medicine, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-913, Brazil; D'Or Institute for Research and Education (IDOR), Botafogo, Rio de Janeiro, 22281-100, Brazil.
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Shi P, Liu J, Liang A, Zhu W, Fu J, Wu X, Peng Y, Yuan S, Wu X. Application of metagenomic next-generation sequencing in optimizing the diagnosis of ascitic infection in patients with liver cirrhosis. BMC Infect Dis 2024; 24:503. [PMID: 38769522 PMCID: PMC11107059 DOI: 10.1186/s12879-024-09396-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Accepted: 05/09/2024] [Indexed: 05/22/2024] Open
Abstract
BACKGROUND Metagenomic next-generation sequencing (mNGS) is an emerging technique for the clinical diagnosis of infectious disease that has rarely been used for the diagnosis of ascites infection in patients with cirrhosis. This study compared mNGS detection with conventional culture methods for the on etiological diagnosis of cirrhotic ascites and evaluated the clinical effect of mNGS. METHODS A total of 109 patients with ascites due to cirrhosis were included in the study. We compared mNGS with conventional culture detection by analyzing the diagnostic results, pathogen species and clinical effects. The influence of mNGS on the diagnosis and management of ascites infection in patients with cirrhosis was also evaluated. RESULTS Ascites cases were classified into three types: spontaneous bacterial peritonitis (SBP) (16/109, 14.7%), bacterascites (21/109, 19.3%) and sterile ascites (72/109, 66.1%). In addition, 109 patients were assigned to the ascites mNGS-positive group (80/109, 73.4%) or ascites mNGS-negative group (29/109, 26.6%). The percentage of positive mNGS results was significantly greater than that of traditional methods (73.4% vs. 28.4%, P < 0.001). mNGS detected 43 strains of bacteria, 9 strains of fungi and 8 strains of viruses. Fourteen bacterial strains and 3 fungal strains were detected via culture methods. Mycobacteria, viruses, and pneumocystis were detected only by the mNGS method. The mNGS assay produced a greater polymicrobial infection rate than the culture method (55% vs. 16%). Considering the polymorphonuclear neutrophil (PMN) counts, the overall percentage of pathogens detected by the two methods was comparable, with 87.5% (14/16) in the PMN ≥ 250/mm3 group and 72.0% (67/93) in the PMN < 250/mm3 group (P > 0.05). Based on the ascites PMN counts combined with the mNGS assay, 72 patients (66.1%) were diagnosed with ascitic fluid infection (AFI) (including SBP and bacterascites), whereas based on the ascites PMN counts combined with the culture assay, 37 patients (33.9%) were diagnosed with AFI (P < 0.05). In 60 (55.0%) patients, the mNGS assay produced positive clinical effects; 40 (85.7%) patients had their treatment regimen adjusted, and 48 patients were improved. The coincidence rate of the mNGS results and clinical findings was 75.0% (60/80). CONCLUSIONS Compared with conventional culture methods, mNGS can improve the detection rate of ascites pathogens, including bacteria, viruses, and fungi, and has significant advantages in the diagnosis of rare pathogens and pathogens that are difficult to culture; moreover, mNGS may be an effective method for improving the diagnosis of ascites infection in patients with cirrhosis, guiding early antibiotic therapy, and for reducing complications related to abdominal infection. In addition, explaining mNGS results will be challenging, especially for guiding the treatment of infectious diseases.
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Affiliation(s)
- Pei Shi
- Department of Infectious Diseases, The First Affiliated Hospital of Nanchang University, No.17 Yongwaizheng Street, Donghu District, Nanchang, Jiangxi Province, China
| | - Juan Liu
- Department of Infectious Diseases, The First Affiliated Hospital of Nanchang University, No.17 Yongwaizheng Street, Donghu District, Nanchang, Jiangxi Province, China
| | - An Liang
- Department of Infectious Diseases, The First Affiliated Hospital of Nanchang University, No.17 Yongwaizheng Street, Donghu District, Nanchang, Jiangxi Province, China
| | - Wentao Zhu
- Department of Infectious Diseases, The First Affiliated Hospital of Nanchang University, No.17 Yongwaizheng Street, Donghu District, Nanchang, Jiangxi Province, China
| | - Jiwei Fu
- Department of Infectious Diseases, The First Affiliated Hospital of Nanchang University, No.17 Yongwaizheng Street, Donghu District, Nanchang, Jiangxi Province, China
| | - Xincheng Wu
- Department of Infectious Diseases, The First Affiliated Hospital of Nanchang University, No.17 Yongwaizheng Street, Donghu District, Nanchang, Jiangxi Province, China
| | - Yuchen Peng
- Department of Infectious Diseases, The First Affiliated Hospital of Nanchang University, No.17 Yongwaizheng Street, Donghu District, Nanchang, Jiangxi Province, China
| | - Songsong Yuan
- Department of Infectious Diseases, The First Affiliated Hospital of Nanchang University, No.17 Yongwaizheng Street, Donghu District, Nanchang, Jiangxi Province, China.
| | - Xiaoping Wu
- Department of Infectious Diseases, The First Affiliated Hospital of Nanchang University, No.17 Yongwaizheng Street, Donghu District, Nanchang, Jiangxi Province, China.
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Fortuny M, Sarrias MR, Torner M, Iborra I, Clos A, Ardèvol A, Bartolí R, Morillas RM, Domènech E, Masnou H. Systematic review of the role of calprotectin in cirrhosis. Eur J Clin Invest 2024; 54:e14111. [PMID: 37849372 DOI: 10.1111/eci.14111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 09/16/2023] [Accepted: 09/23/2023] [Indexed: 10/19/2023]
Abstract
BACKGROUND Calprotectin is a calcium-binding-S100-protein synthetized mainly in neutrophils which has been demonstrated to be an accurate biomarker of the presence of these cells. Gut barrier dysfunction in patients with advanced chronic liver disease (ACLD), in addition to the lack of noninvasive tools for diagnosis and prognosis of cirrhosis decompensations, has raised interest in this biomarker. AIMS Our aim is to summarize the current evidence regarding the role of calprotectin in terms of its diagnostic and prognostic utility in ACLD. METHODS We performed a systematic search (PROSPERO registration no. CRD42023389069) of original articles published without any restrictions on the publication date until January 2023 providing information about calprotectin for the prognosis or diagnosis of ACLD and its decompensations in adult patients. RESULTS A total 227 articles were identified, and 26 observational studies finally met the inclusion criteria. In 14 studies, calprotectin was measured in ascitic fluid, all of which reported higher calprotectin values in spontaneous bacterial peritonitis, while cut-off points for its diagnosis were proposed in nine studies. Three studies reported higher faecal calprotectin levels in patients with hepatic encephalopathy and portal hypertension. Four studies evaluated faecal calprotectin and one plasma calprotectin as biomarkers for gut barrier integrity and bacterial translocation. CONCLUSIONS Calprotectin is emerging as a promising biomarker in ACLD, particularly for the management of bacterial infections and alcohol-related liver disease. Further research with better study designs should help to determine the feasibility of calprotectin measurement in routine clinical practice.
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Affiliation(s)
- Marta Fortuny
- Hepatology Unit, Hospital Germans Trias i Pujol, Badalona, Spain
- Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Maria-Rosa Sarrias
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain
| | - Maria Torner
- Hepatology Unit, Hospital Germans Trias i Pujol, Badalona, Spain
| | - Ignacio Iborra
- Hepatology Unit, Hospital Germans Trias i Pujol, Badalona, Spain
- Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Ariadna Clos
- Hepatology Unit, Hospital Germans Trias i Pujol, Badalona, Spain
| | - Alba Ardèvol
- Hepatology Unit, Hospital Germans Trias i Pujol, Badalona, Spain
| | - Ramon Bartolí
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain
| | - Rosa M Morillas
- Hepatology Unit, Hospital Germans Trias i Pujol, Badalona, Spain
- Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Eugeni Domènech
- Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- IBD Unit, Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
| | - Helena Masnou
- Hepatology Unit, Hospital Germans Trias i Pujol, Badalona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
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Sbeit W, Maamoun B, Azzam S, Shahin A, Carmiel-Haggai M, Khoury T. Ascites fluid calprotectin level is highly accurate in diagnosing spontaneous bacterial peritonitis: a preliminary proof of concept prospective study. Clin Exp Med 2024; 24:25. [PMID: 38281236 PMCID: PMC10822801 DOI: 10.1007/s10238-023-01257-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Accepted: 12/15/2023] [Indexed: 01/30/2024]
Abstract
Ascites is the most common complication of liver cirrhosis. Spontaneous bacterial peritonitis (SBP) is a common complication of ascites. The diagnosis is made by an ascitic fluid polymorphonuclear (PMN) cell count of ≥ 250/mm3. However, no other diagnostic test is present for the diagnosis of SBP. The aim of the study present study is to assess the diagnostic yield of ascitic calprotectin in SBP, and to explore whether it can predict disease stage. We performed a single center proof-of-concept prospective study including all patients with cirrhosis and ascites who underwent paracentesis. Overall, 31 patients were included in the study. Eight patients had SBP vs. 23 patients without SBP. Ascitic calprotectin level was 77.4 ± 86.5 μg/mL in the SBP group, as compared to 16.1 ± 5.6 μg/mL in the non-SBP group (P = 0.001). An ascitic calprotectin cut-off value of > 21 μg/mL was associated with sensitivity and specificity of 85.7% and 89.5%, respectively, with ROC of 0.947 (95% CI 0.783 to 0.997, P < 0.0001). Notably, ascitic calprotectin did not had a prognostic value in cirrhosis stage and prognosis. Ascitic calprotectin was highly accurate in the diagnosis of SBP. It can be a serve as adjunct for indefinite cases of SBP.
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Affiliation(s)
- Wisam Sbeit
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, 1311502, Israel
| | - Basheer Maamoun
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, 1311502, Israel
| | - Subhi Azzam
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel
| | - Amir Shahin
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, 1311502, Israel
| | - Michal Carmiel-Haggai
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, 1311502, Israel
- Liver Unit, Galilee Medical Center, Nahariya, Israel
| | - Tawfik Khoury
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel.
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, 1311502, Israel.
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Mid-Infrared Spectroscopy as a New Tool for Ruling Out Spontaneous Bacterial Peritonitis: A Proof-of-Concept Study. Biomedicines 2023; 11:biomedicines11030838. [PMID: 36979817 PMCID: PMC10045833 DOI: 10.3390/biomedicines11030838] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2023] [Revised: 03/01/2023] [Accepted: 03/06/2023] [Indexed: 03/12/2023] Open
Abstract
Background and aims: A highly sensitive and specific point-of-care method for diagnosing spontaneous bacterial peritonitis (SBP) is currently lacking. The objective of the present study is to evaluate the diagnostic value of a rapid, easy-to-use, mid-infrared fiber evanescent wave spectroscopy (MIR-FEWS) method for ruling out SBP. Patients and Methods: Cirrhotic patients (n = 256) at five centers in France were included for suspected SBP or for the scheduled evacuation of ascites fluid. The mid-infrared spectrum of 7 µL of an ascites fluid sample was recorded using a MIR-FEWS system. To define a model for the diagnosis of SBP, the patients were divided into a calibration group (n = 170) and a validation group (n = 86). Results: Most of the patients were male (71%). The mean age was 60.25 years. Alcohol-related liver disease was the most common cause of cirrhosis. SBP was observed in 18% of the patients. For the diagnosis of SBP in the calibration and validation groups, respectively, the model gave areas under the receiver operating characteristic curves of 0.87 and 0.89, sensitivities of 90% and 87%, specificities of 78% and 80%, positive predictive values of 48% and 50%, negative predictive values of 97% and 96%, positive likelihood ratio of 4.09 and 4.35, negative likelihood ratio of 0.13 and 0.16, Youden index of 0.68 and 0.67, and correct classification rates of 80% and 81%. Conclusion: The results of this proof-of-concept study show that MIR-FEWS is a highly sensitive diagnostic method for ruling out SBP. The method warrants further investigation.
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Kostanjšak T, Bojanić K, Čičak H, Gotić J, Vrbanac Z, Šimundić AM, Vnuk D, Bottegaro NB. Is canine calprotectin in serum stabile after storage at low temperature? BMC Vet Res 2022; 18:451. [PMID: 36564781 PMCID: PMC9789605 DOI: 10.1186/s12917-022-03534-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 11/29/2022] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND In human and veterinary medicine calprotectin is most widely used in diagnosing different gastro-intestinal diseases. The aim of this study was to assess the stability of canine calprotectin (cCP) in serum after storage at low temperatures and imprecision of the method. METHODS Blood samples were collected from dogs with different clinical diagnoses. Twenty-two dogs were included in this study. Calprotectin concentration was measured 4 hours after serum separation (T0), and after being frozen at - 80 °C for 8 (T1) and 16 weeks (T2). The maximum permissible difference (MPD) was derived from the equation for calculating total error (TE) TE = %Bias + (1.96 x %CV), where bias and coefficient of variation (CV) were defined by the manufacturer. The dogs enrolled in this study were patients admitted during the morning (9-12 a.m.), on the day the first measurement was performed. All sample analysis for determination of stability were done in duplicates. For determination of within-run precision, the two patients' serum samples were analyzed in 20 replicates. Imprecision was assessed by analyzing 20 replicates on one plate on two samples where high and low concentrations were anticipated. RESULTS The calculated value of MPD was 32.52%. Median calprotectin concentrations were higher at T1 114.08 μg/L (IQR = 55.05-254.56) and T2 133.6 μg/L (IQR = 100.57-332.98) than at T0 83.60 μg/L (IQR = 50.38-176.07). Relative and absolute bias at T1 (49.3%; 45.98 μg/L) and T2 (109.93%; 94.09 μg /L) have shown that calprotectin concentrations increase after long term storage at - 80 °C. CONCLUSION The results of the present study indicate that c-CP was not stable for 16 weeks at low storage temperature (- 80 °C). Considering the observed change in the concentration of c-CP at T1, a storage time of 8 weeks should be safely applied. The method imprecision was not satisfactory, especially in the lower concentration range.
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Affiliation(s)
- Tara Kostanjšak
- grid.4808.40000 0001 0657 4636Clinic for surgery, orthopaedics and ophthalmology, Faculty of Veterinary medicine, University of Zagreb, Zagreb, Croatia
| | - Krunoslav Bojanić
- grid.4905.80000 0004 0635 7705Laboratory for Aquaculture Biotechnology, Division of Materials Chemistry, Ruđer Bošković Institute, Zagreb, Croatia
| | - Helena Čičak
- grid.412688.10000 0004 0397 9648Department of Medical Laboratory Diagnostics, University Hospital “Sveti Duh”, Zagreb, Croatia
| | - Jelena Gotić
- grid.4808.40000 0001 0657 4636Clinic for Internal Medicine, Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia
| | - Zoran Vrbanac
- grid.4808.40000 0001 0657 4636Department of Radiology, Ultrasound Diagnostic and Physical Therapy, Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia
| | - Ana-Maria Šimundić
- grid.412688.10000 0004 0397 9648Department of Medical Laboratory Diagnostics, University Hospital “Sveti Duh”, Zagreb, Croatia
| | - Dražen Vnuk
- grid.4808.40000 0001 0657 4636Clinic for surgery, orthopaedics and ophthalmology, Faculty of Veterinary medicine, University of Zagreb, Zagreb, Croatia
| | - Nika Brkljača Bottegaro
- grid.4808.40000 0001 0657 4636Clinic for surgery, orthopaedics and ophthalmology, Faculty of Veterinary medicine, University of Zagreb, Zagreb, Croatia
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10
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Verma R, Satapathy SK, Bilal M. Procalcitonin and C-reactive protein in the diagnosis of spontaneous bacterial peritonitis. Transl Gastroenterol Hepatol 2022; 7:36. [PMID: 36300145 PMCID: PMC9468983 DOI: 10.21037/tgh-19-297] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Accepted: 05/12/2021] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Spontaneous bacterial peritonitis (SBP) is a serious complication of cirrhosis and is associated with high morbidity and mortality. Rapid institution of appropriate antibiotics is central to the improved patient outcome. Correctly obtaining ascites fluid for analysis has several technical and logistic limitations resulting in overuse of empiric antibiotics when patients are admitted to the hospital with suspected SBP. Procalcitonin and C-reactive protein (CRP) are non-invasive markers of infection. We conducted a study to illustrate the role of these markers in making the diagnosis of SBP in patients with cirrhosis. METHODS A total of 45 patients were enrolled in this prospective cohort study, 14 (31.1%) of which were found to have SBP. Ascitic fluid neutrophils, serum procalcitonin and CRP levels were measured prior to initiation of antibiotics and these parameters were compared between the two groups. Area under receiver operator characteristic (AUROC) curves were used to assess the diagnostic accuracy of procalcitonin and CRP in this population. We defined neutrocytic SBP group as a combination of patients who had classic SBP (positive ascitic culture and >250 neutrophils/mm3) and culture-negative neutrocytic ascites. RESULTS Serum procalcitonin (2.81±2.59 vs. 0.43±0.48 ng/mL; P=0.0032), serum CRP (60.30±44.48 vs. 22.2±23.28; P=0.0055) and ascitic fluid neutrophil levels (49.23±30.90 vs. 16.7±20.39; P=0.0064) were significantly higher in SBP group than non-SBP group. AUROC for procalcitonin (cut-off >2.0 ng/mL) was 0.75 (95% CI, 0.61-0.88), CRP (cut-off >3.0 mg/L) was 0.55 (95% CI, 0.43-0.68) and for procalcitonin combined with CRP was 0.76 (95% CI, 0.61-0.90) for diagnosing all-cause SBP. In a subgroup analysis of patients with neutrocytic SBP, AUROC for procalcitonin was 0.88 (95% CI, 0.74-1.00), CRP was 0.62 (95% CI, 0.45-0.79) and for procalcitonin combined with CRP was 0.93 (95% CI, 0.81-1.00). Addition of CRP to procalcitonin did not significantly change the AUROC for diagnosis of SBP. CONCLUSIONS Serum procalcitonin could be used as an adjunctive non-invasive biomarker in diagnosing SBP with a high degree of accuracy in cirrhotic patients. Addition of CRP does not seem to significantly increase the diagnostic accuracy of procalcitonin.
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Affiliation(s)
- Rajanshu Verma
- Transplant Hepatology/Gastroenterology fellow, University of Tennessee Health Sciences Center, Memphis, TN, USA
| | - Sanjaya K. Satapathy
- Department of Transplant Surgery, Methodist University Hospital Transplant Institute/University of Tennessee Health Sciences Center, Memphis, TN, USA
- Medical Director of Liver Transplantation, Division of Hepatology, Sandra Atlas Bass Center for Liver Diseases and Liver Transplantation, Northwell Health/North Shore University Hospital, Manhasset, New York, USA
| | - Muhammad Bilal
- Department of Gastroenterology, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA
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11
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Patel KP, Korbitz PM, Gallagher JP, Schmidt C, Ingviya T, Manatsathit W. Ascitic calprotectin and lactoferrin for detection of spontaneous bacterial peritonitis: a systematic review and meta-analysis. Transl Gastroenterol Hepatol 2022; 7:37. [PMID: 36300150 PMCID: PMC9468990 DOI: 10.21037/tgh-20-323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 02/26/2021] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND Spontaneous bacterial peritonitis (SBP) is a common bacterial infection in cirrhotic patients associated with a high mortality rate. Prompt diagnosis and early antibiotic administration are crucial in minimizing adverse outcomes. Although detection of ≥250 polymorphonuclear leukocytes (PMN) in ascitic fluid is the current gold standard to diagnose SBP, consideration for rapid detection with biomarkers is warranted. METHODS A literature search for studies evaluating ascitic calprotectin and lactoferrin for detection of SBP was performed using PubMed, Embase, Scopus, Google Scholar, Cochrane library, and Clinical Trial Registries. Summary sensitivity, specificity, log diagnostic odds ratio (LDOR), and area under the summary receiver operating curve (AUC) were calculated. RESULTS In total, 12 and 13 studies evaluated ascitic calprotectin and lactoferrin, respectively, for detection of SBP. Summary sensitivity, specificity, and LDOR for calprotectin were 0.942 (95% CI, 0.916, 0.967), 0.860 (95% CI, 0.799, 0.935), and 4.250 (95% CI, 3.504, 4.990), respectively. AUC for calprotectin was 0.91. Summary sensitivity, specificity, and LDOR for lactoferrin were 0.954 (95% CI, 0.930, 0.979), 0.890 (95% CI, 0.836, 0.945), and 4.630 (95% CI, 3.800, 5.452), respectively. AUC for lactoferrin was 0.958. CONCLUSIONS The overall performance of ascitic calprotectin and lactoferrin was substantial, potentially serving as a screening tool or an alternative to manual cell count. However, a variety of manufacturers, cut-off values, and significant heterogeneity between studies should be noted. Point-of-care testing for calprotectin and lactoferrin may resolve disadvantages associated with the current methods. Future studies on this topic are, therefore, needed.
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Affiliation(s)
- Kishan P. Patel
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA
| | - Parker M. Korbitz
- Department of Internal Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - John P. Gallagher
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA
| | - Cynthia Schmidt
- McGoogan Library of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
| | - Thammasin Ingviya
- Department of Family and Preventive Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
- Medical Data Center for Research and Innovation, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
- Digital Innovation and Data Analytics, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
| | - Wuttiporn Manatsathit
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA
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Khilnani GC, Tiwari P, Zirpe KG, Chaudhry D, Govil D, Dixit S, Kulkarni AP, Todi SK, Hadda V, Jain N, Govindagoudar MB, Samavedam S, Jha SK, Tyagi N, Jaju MR, Sharma A. Guidelines for the Use of Procalcitonin for Rational Use of Antibiotics. Indian J Crit Care Med 2022; 26:S77-S94. [PMID: 36896360 PMCID: PMC9989870 DOI: 10.5005/jp-journals-10071-24326] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Accepted: 10/21/2022] [Indexed: 11/07/2022] Open
Abstract
How to cite this article: Khilnani GC, Tiwari P, Zirpe KG, Chaudhary D, Govil D, Dixit S, et al. Guidelines for the Use of Procalcitonin for Rational Use of Antibiotics. Indian J Crit Care Med 2022;26(S2):S77-S94.
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Affiliation(s)
- Gopi C Khilnani
- Department of Pulmonary, Critical Care and Sleep Medicine, PSRI Hospital, New Delhi, India
| | - Pawan Tiwari
- Department of Pulmonary Medicine, School of Excellence in Pulmonary Medicine, Netaji Subhash Chandra Bose Medical College, Jabalpur, Madhya Pradesh, India
| | | | - Dhruva Chaudhry
- Department of Pulmonary and Critical Care Medicine, Pandit Bhagwat Dayal Sharma University of Health Sciences, Rohtak, Haryana, India
| | - Deepak Govil
- Institute of Critical Care and Anesthesia, Medanta - The Medicty, Gurugram, Haryana, India
| | - Subhal Dixit
- Department of Critical Care Medicine, Sanjeevan Surgery Hospital, Pune, Maharashtra, India; Department of Critical Care Medicine, MJM Hospital, Pune, Maharashtra, India
| | - Atul Prabhakar Kulkarni
- Department of Anaesthesia, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | | | - Vijay Hadda
- Department of Pulmonary, Critical Care and Sleep Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Neetu Jain
- Department of Pulmonary Medicine, Critical Care and Sleep Disorders, Pushpawati Singhania Hospital & Research Institute, New Delhi, India
| | | | - Srinivas Samavedam
- Department of Critical Care Management, Virinchi Hospital, Hyderabad, Telangana, India
| | | | - Niraj Tyagi
- Department of Institute of Critical Care Medicine, Sir Ganga Ram Hospital, New Delhi, India
| | - Madhusudan R Jaju
- Critical Care Medicine Sunshine Hospital, Gachibowli, Hyderabad, India
| | - Anita Sharma
- Department of Lab Medicine, Fortes Hospital, Mohali, Punjab, India
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Honar N, Nezamabadipour N, Dehghani SM, Haghighat M, Imanieh MH, Ataollahi M, Shakibazad N, Javaherizadeh H. An evaluation of ascitic calprotectin for diagnosis of ascitic fluid infection in children with cirrhosis. BMC Pediatr 2022; 22:382. [PMID: 35773636 PMCID: PMC9245209 DOI: 10.1186/s12887-022-03433-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 06/21/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The most common infection in children with the hepatic disease with or without cirrhotic ascites is spontaneous bacterial peritonitis (SBP), which occurs in the absence of an evident intra-abdominal source of infection. The present study aims to assess the value of calprotectin in ascitic fluid in the diagnosis of ascitic fluid infection in children with liver cirrhosis. MATERIALS AND METHODS In this cross-section study, 80 children with underlying liver disease who attended the Hepatology and Emergency Department in Shiraz University Hospitals were studied. All the patients were evaluated by a thorough history, clinical examination, laboratory investigations, diagnostic paracentesis with PMNLs count, and Calprotectin, which was measured in 1 mL ascitic fluid by ELISA. RESULTS Thirty-five patients (43.75%) were diagnosed with ascitic fluid infection. Of these children 6 cases had positive ascitic fluid culture (SBP). Calprotectin was high in AFI patients with a statistically significant difference in AFI patients compared to non-AFI patients. The cut-off levels were 91.55 mg /L and the area under the curve was 0.971. So it can serve as a sensitive and specific diagnostic test for detection of AFI in children with underlying liver disease. CONCLUSION Elevated ascitic calprotectin levels in cirrhotic patients are a diagnostic and reliable marker for the detection of AFI and are considered a surrogate marker for PMN.
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Affiliation(s)
- Naser Honar
- Neonatal Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Najmeh Nezamabadipour
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyed Mohsen Dehghani
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mahmood Haghighat
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad Hadi Imanieh
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Maryam Ataollahi
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Nader Shakibazad
- Department of Pediatrics, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Hazhir Javaherizadeh
- Alimentary Tract Research Center, Clinical Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
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Barutcu S, Yildirim AE, Sahin A, Gulsen MT. Lymphocyte to Monocyte Ratio and C-Reactive Protein Combination as the Best Simple Predictor of Treatment Response in Cirrhotic Patients with Culture Negative Neutrocytic Ascites. SISLI ETFAL HASTANESI TIP BULTENI 2022; 56:77-83. [PMID: 35515960 PMCID: PMC9040302 DOI: 10.14744/semb.2021.58219] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 06/28/2021] [Indexed: 06/14/2023]
Abstract
OBJECTIVES The aim of this study was to evaluate the most ideal inflammatory markers for treatment response and to determine a cutoff value that could predict response to treatment for culture negative neutrocytic ascite (CNNA) patients. METHODS This is a retrospective cross-sectional case-controlled study. Patients with CNNA were evaluated by taking ascites fluid sampling at the beginning and on the 5th day of treatment. Neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and neutrophil-to-monocyte ratio were calculated. RESULTS Of the 123 cases with cirrhotic ascites disease, 59 were CCNA and 64 were the control group without ascite-fluid infection. There were statistically significant differences for blood monocyte count, NLR (p<0.01), LMR, and C-reactive protein (CRP) (p<0.001) between two groups. Patients in the CNNA group were compared before and after treatment among themselves for the treatment response. There was statistically significant difference in mean platelet volume, monocyte, LMR, and CRP (p<0.05) between two groups. After receiver operator characteristics curve analysis, the best cutoff value for monocyte was <0.64 × 103/μL (sensitivity 49.2%, specificity 74.6%, positive predictive value [PPV] 65.9%, and negative predictive value [NPV] 59.5%) (p<0.01), for LMR was ≥1.7 (sensitivity 76.3%, specificity 78%, PPV 77.6%, and NPV 76.7%), and for CRP was ≤18 mg/L (sensitivity 91.5% specificity 57.6%, PPV 68.4%, and NPV 87.2%) (p<0.001). When LMR and CRP were used together, sensitivity (86.5%), specificity (83.1%), PPV (83.6%), and NPV (86%) were found to be statistically significantly higher (p<0.001). CONCLUSION Our results showed that in cirrhotic patients with CNNA, combined LMR + CRP can be used as a novel, low cost and non-invasive test to predict treatment response.
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Affiliation(s)
- Sezgin Barutcu
- Division of Gastroenterology, Gaziantep University Faculty of Medicine, Gaziantep, Turkey
| | - Abdullah Emre Yildirim
- Division of Gastroenterology, Gaziantep University Faculty of Medicine, Gaziantep, Turkey
| | - Ahmet Sahin
- Department of Infectious Disease and Clinical Microbiology, University of Health Sciences Turkey, Mehmet Akif Inan Research and Training Hospital, Şanlıurfa, Turkey
| | - Murat Taner Gulsen
- Department of Infectious Disease and Clinical Microbiology, University of Health Sciences Turkey, Mehmet Akif Inan Research and Training Hospital, Şanlıurfa, Turkey
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Diagnostic Potential of Calprotectin for Spontaneous Bacterial Peritonitis in Patients Withliver Cirrhosis and Ascites. Pril (Makedon Akad Nauk Umet Odd Med Nauki) 2021; 42:97-106. [PMID: 35032370 DOI: 10.2478/prilozi-2021-0040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
The development of spontaneous bacterial peritonitis (SBP) is a serious and life-threatening condition in patients with cirrhosis and ascites. The aim of this study was to determine the diagnostic potential of calprotectin in ascites, for SBP in patients with liver cirrhosis and ascites before and after antibiotic treatment and to compare the mean values of calprotectin in ascites in patients with and without SBP. This prospective-observational study was comprised of 70 patients with cirrhosis and ascites, divided into two groups, the SBP and the non-SBP group. Quantitative measurements of calprotectin in ascites was completed with the Quantum Blue Calprotectin Ascites test (LF-ASC25), using the Quantum Blue Reader. The average value of calprotectin in the SBP group was 1.5 ± 0.40 μg / mL, and in the non-SBP group it was lower (0.4 ± 0.30). The difference between the mean values was statistically significant with p <0.05. The mean value of calprotectin in ascites before therapy among the SBP group was 1.5 ± 0.4, and after antibiotic therapy, the value decreased significantly to 1.0 ± 0.6; the difference between the mean values was statistically significant with p <0.05. ROC analysis indicated that calprotectin contributed to the diagnosis of SBP with a 94.3% sensitivity rating (to correctly identify positives), and the specificity was 62.5%, which corresponded to the value of 0.275. Our research confirmed that ascitic calprotectin was a good predictor, and is significantly associated with the occurrence of SBP in patients with liver cirrhosis. By monitoring the value of calprotectin in ascites on the 7th day of antibiotic treatment, the effectiveness of antibiotic treatment in patients with SBP can be determined.
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El-Hassib DMA, Abo-elmatty DM, Mesbah NM, Abd-Elsalam S, Bastawisy SA, E. D, Hassan AS, Zahran FE, Abdelghany RS, Siddik RI, Abdel-Hamed AR. The Role of MicroRNAs (miRNA 155, miRNA-146b) and Procalcitonin as Novel Markers for the Diagnosis of Spontaneous Bacterial Peritonitis. THE OPEN BIOMARKERS JOURNAL 2021; 11:28-38. [DOI: 10.2174/1875318302111010028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Revised: 12/21/2020] [Accepted: 01/25/2021] [Indexed: 09/01/2023]
Abstract
Background:MircoRNAs are endogenous, small non-coding RNA molecules that have been recognized as important modulators of gene expression. MicroRNA is considered one of the potential biomarkers of infection and inflammation. Our study aims to identify the potential role of miRNA-155, miRNA-146b, and Procalcitonin (PCT) in the early detection of spontaneous bacterial peritonitis in cirrhotic liver patients. miRNA-155 and 146b are molecular biomarkers , while procalcitonin is a serum marker in ascites patients complicated with Spontaneous Bacterial Peritonitis (SBP) .Methods:This study was conducted on 199 patients, 101 of them have ascites complicated with spontaneous bacterial peritonitis, and 98 patients without spontaneous bacterial peritonitis (control group). Ascitic fluid samples were collected from patients with SBP undergoing paracentesis at National Hepatology Institute in Egypt. MicroRNAs were determined in the serum using qPCR (quantitative polymerase chain reaction), while procalcitonin has been assessed in serum samples using ELISA (Enzyme-linked immune assay) technique.Results:Serum levels of miRNA-146b & miRNA-155 were significantly higher (p<0.001) in spontaneous bacterial peritonitis patients (79.2% and 97.0% respectively) than ascites patients (17.3% and 7.1%, respectively). Furthermore, the serum level of procalcitonin was significantly higher (p<0.001) in spontaneous bacterial peritonitis patients than that in ascites patients (68.3% and 27.6%, respectively).Conclusion:miRNA-155, miRNA-146b and procalcitonin can be used as early markers for the detection of SBP in hepatic patients with ascites.
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The diagnostic accuracy of ascitic calprotectin for the early diagnosis of spontaneous bacterial peritonitis: systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2021; 33:312-318. [PMID: 32541235 DOI: 10.1097/meg.0000000000001813] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Spontaneous bacterial peritonitis (SBP) is a common complication in patients with cirrhosis and has an incidence of up to 30% in hospitalized patients. Importantly, it may raise their mortality rate up to 30%. Hence, a delayed diagnosis is associated with poor prognosis. This systematic review aims to assess the diagnostic accuracy of ascitic fluid calprotectin for the early diagnosis of SBP in patients with ascites. This study was conducted in accordance with the PRISMA statement. A systematic literature search was conducted from inception to February 2020 in the following electronic bibliographic databases: MEDLINE, Scopus, The Cochrane Library and OpenGrey. Quality Assessment of Diagnostic Accuracy Studies tool was used to assess risk of bias. Ten studies were included in the qualitative and quantitative synthesis. Hierarchical summary receiver operating characteristic curves were plotted and the summary sensitivity of a positive ascitic fluid calprotectin assessment to detect SBP was 93% [95% confidence interval (CI) 90-95%] while the summary specificity was 89% (95% CI 80-95%), irrespectively of the method used. The positive likelihood ratio and negative likelihood ratio of the test were 8.7 (95% CI 4.4-17.1) and 0.08 (85% CI 0.06-0.12). All studies showed positive correlation between ascitic calprotectin and polymorphonuclear (PMN) leukocyte count. Ascitic calprotectin appears to be an excellent alternative to PMN leucocyte count of ≥250 cells/mm3 for the diagnosis of SBP with much faster time to diagnosis. Owing to its substantially high negative predictive value, the test can accurately exclude SBP avoiding unnecessary antibiotics in suspected patients.
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The Diagnostic Value of CD11b Expression on Peripheral Blood Neutrophils for Detection of Spontaneous Bacterial Peritonitis. GASTROENTEROLOGY INSIGHTS 2021. [DOI: 10.3390/gastroent12010003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background: Spontaneous bacterial peritonitis (SBP) is associated with the highest mortality among end-stage cirrhotic liver disease patients. Neutrophil CD11b expression increases on the neutrophil surface within 5 min of exposure to bacteria. Paracentesis remains the only accepted method for accurate evaluation of patients, with many drawbacks; hence, a diagnostic noninvasive marker with a very high sensitivity and high diagnostic accuracy is very necessary. Aim of the study: to evaluate the neutrophil CD11b as a non-invasive biomarker for the diagnosis of SBP, comparing its sensitivity and specificity to other traditional methods. Patients and Methods: 200 patients who had liver cirrhosis with ascites were recruited to the Hepatology department inpatient wards of the National Liver Institute, Menoufia University. They were divided into Group I: 100 patients with SBP and Group II: 100 patients with non SBP ascites. All studied patients were subjected to full clinical examination, abdominal ultrasound, paracentesis, and laboratory investigations including ascetic fluid (AF) examinations. The CD11b expression and its mean fluorescence intensity (MFI) were assessed on peripheral blood neutrophils by flowcytometry. Results: There was a significant increase in the MFI of CD11b in the SBP group compared to the non SBP group. At cut off >20 for MFI of CD11b with a sensitivity of 100% and specificity of 100% can discriminate between SBP and non SBP cases followed by ascetic fluid TLC examination at a cut off 0.26 (×103) with a sensitivity of 92%, and specificity of 96%, then, AF neutrophil count at cut off 0.25 (×103) with a sensitivity of 80%, specificity of 100%, and AF culture examination with a sensitivity of 56% and specificity of 100%. Conclusion: The measurement of CD11b MFI on peripheral blood neutrophils is a useful non-invasive marker with high sensitivity and specificity to predict SBP compared with other methods. Further large-scale studies are needed to study the value of CD11b MFI level in the SBP follow-up therapy.
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Abdel Rahman EM, Attia FA, Alsebaey A, Elkady MAK, Sayed MM, Reda Awad A, El-Seidi EA. Ascitic calprotectin as a useful marker in the diagnosis of spontaneous bacterial peritonitis in adults. EGYPTIAN LIVER JOURNAL 2020; 10:14. [DOI: 10.1186/s43066-020-0022-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Accepted: 01/23/2020] [Indexed: 02/08/2023] Open
Abstract
Abstract
Background
Ascitic fluid polymorphonuclear leucocyte count (PMN) is known to be the gold standard for spontaneous bacterial peritonitis (SBP) diagnosis. The aim of this work was to assess ascitic calprotectin for SBP diagnosis. Serum C-reactive protein (CRP), high sensitivity C-reactive protein (hsCRP), nitrous oxide, ascitic PMN, ascitic leucocyte esterase and ascitic calprotectin were measured.
Results
The average age of our patients was 55.25 ± 7.89 years, mostly males (n = 51, 63.8%), anti-HCV antibodies were positive in (n = 61, 76.3%). Sixty-four patients (80%) were Child-Pugh C and their average MELD was 24.29 ± 8.06. Patients with SBP had statistically significant higher median MELD score (26.5 vs. 19) and higher average Child-Pugh score (12.18 ± 1.74 vs. 10.5 ± 1.97). Forty patients had SBP and 40 patients were without SBP. Both the serum and ascitic nitrous oxide did not differ statistically between patients with and without SBP. In contrast, patients with SBP had higher median serum CRP (49 vs. 12 mg/dL), hsCRP (58,000 vs. 23,750 ng/dL) and ascitic calprotectin (7.57 vs. 1.1 ng/mL). The ascitic leucocyte esterase test was positive in 95% of SBP patients in contrast to 2.5% patients without SBP. Ascitic calprotectin >2 ng/mL had 90% sensitivity, 92.5% specificity, 92.3% positive predictive value and 90.2% negative predictive value. MELD, CRP, hsCRP and ascitic calprotectin are independent predictors of SBP.
Conclusion
Ascitic calprotectin is a useful marker for SBP diagnosis.
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Mayr U, Lukas M, Elnegouly M, Vogt C, Bauer U, Ulrich J, Schmid RM, Huber W, Lahmer T. Ascitic Interleukin 6 Is Associated with Poor Outcome and Spontaneous Bacterial Peritonitis: A Validation in Critically Ill Patients with Decompensated Cirrhosis. J Clin Med 2020; 9:jcm9092865. [PMID: 32899730 PMCID: PMC7564827 DOI: 10.3390/jcm9092865] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 08/27/2020] [Accepted: 09/02/2020] [Indexed: 02/08/2023] Open
Abstract
Decompensated cirrhosis predisposes to infectious diseases and acute-on-chronic liver failure (ACLF) in critically ill patients. Infections like spontaneous bacterial peritonitis (SBP) are frequently associated with multi-organ failure and increased mortality. Consequently, reliable predictors of outcome and early diagnostic markers of infection are needed to improve individualized therapy. This study evaluates the prognostic role of ascitic interleukin 6 in 64 patients with cirrhosis admitted to our intensive care unit (ICU). In addition, we analysed the diagnostic ability of ascitic interleukin 6 in a subgroup of 19 patients with SBP. Baseline ascitic interleukin 6 performed well in predicting 3-month mortality in patients with decompensated cirrhosis (area under curve (AUC) = 0.802), as well as in patients fulfilling ACLF-criteria (AUC = 0.807). Ascitic interleukin 6 showed a moderate prognostic advantage compared with common clinical scores and proinflammatory parameters. Moreover, ascitic interleukin 6 had a sufficient diagnostic ability to detect SBP (AUC = 0.901) and was well correlated with ascitic polymorphonuclear neutrophils in SBP (p = 0.002). Interestingly, ascitic interleukin 6 revealed a high predictive value to rule out apparent infections on admission to ICU (AUC = 0.904) and to identify patients with “culture-positive SBP” (AUC = 0.856). Ascitic interleukin 6 is an easily-applicable proinflammatory biomarker with high prognostic and diagnostic relevance in critically ill patients with liver cirrhosis.
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Affiliation(s)
- Ulrich Mayr
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technische Universität München, D-81675 München, Germany; (M.L.); (M.E.); (U.B.); (J.U.); (R.M.S.); (W.H.); (T.L.)
- Correspondence: ; Tel.: +49-89-4140-5226; Fax: +49-89-4140-4742
| | - Marina Lukas
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technische Universität München, D-81675 München, Germany; (M.L.); (M.E.); (U.B.); (J.U.); (R.M.S.); (W.H.); (T.L.)
| | - Mayada Elnegouly
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technische Universität München, D-81675 München, Germany; (M.L.); (M.E.); (U.B.); (J.U.); (R.M.S.); (W.H.); (T.L.)
| | - Christine Vogt
- Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität München, D-81675 München, Germany;
| | - Ulrike Bauer
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technische Universität München, D-81675 München, Germany; (M.L.); (M.E.); (U.B.); (J.U.); (R.M.S.); (W.H.); (T.L.)
| | - Joerg Ulrich
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technische Universität München, D-81675 München, Germany; (M.L.); (M.E.); (U.B.); (J.U.); (R.M.S.); (W.H.); (T.L.)
| | - Roland M. Schmid
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technische Universität München, D-81675 München, Germany; (M.L.); (M.E.); (U.B.); (J.U.); (R.M.S.); (W.H.); (T.L.)
| | - Wolfgang Huber
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technische Universität München, D-81675 München, Germany; (M.L.); (M.E.); (U.B.); (J.U.); (R.M.S.); (W.H.); (T.L.)
| | - Tobias Lahmer
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technische Universität München, D-81675 München, Germany; (M.L.); (M.E.); (U.B.); (J.U.); (R.M.S.); (W.H.); (T.L.)
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Ascitic calprotectin for the diagnosis of spontaneous bacterial peritonitis: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2020; 32:1075-1083. [PMID: 32175980 DOI: 10.1097/meg.0000000000001709] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Calprotectin is a promising diagnostic biomarker for spontaneous bacterial peritonitis (SBP) among cirrhotic patients, but published studies report a wide variation of its diagnostic accuracy. We systematically searched six databases for eligible studies (i.e., all original studies that reported ascitic calprotectin as a diagnostic marker for SBP in cirrhotic patients), and assessed their quality with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. We calculated the pooled sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR), and diagnostic odds ratio (DOR) using the bivariate mixed-effect model. We constructed the summary receiver operating characteristic and determined the area under the curve (AUC). We registered the study protocol in PROSPERO (CRD42019125476). Our search retrieved 102 studies, of which 10 were included in the analysis. The overall risk of bias of these studies ranged from low to moderate. There was no heterogeneity from the threshold effect (Spearman correlation coefficient = 0.100, P value = 0.770). The pooled estimates [95% confidence intervals (CIs)] for ascitic calprotectin were as follows: sensitivity 0.91 (95% CI: 0.88-0.94), specificity 0.87 (95% CI: 0.68-0.96), PLR 7.18 (95% CI: 2.52-20.43), NLR 0.10 (95% CI: 0.07-0.15), DOR 71.91 (95% CI: 19.42-266.34), and AUC 0.92 (95% CI: 0.90-0.94). The sensitivity analysis did not detect outliers, and the model had a robust goodness of fit. There was no significant publication bias detected (Deeks test of asymmetry, P value = 0.79). Ascitic calprotectin is a promising diagnostic biomarker for SBP in cirrhotic patients.
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Nasereslami M, Khamnian Z, Moaddab Y, Jalali Z. Diagnostic and prognostic role of ascitic fluid calprotectin level: six-month outcome findings in cirrhotic patients. Scand J Gastroenterol 2020; 55:1093-1098. [PMID: 32715845 DOI: 10.1080/00365521.2020.1794023] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
AIM To assess the role of ascites calprotectin in early detection of SBP in patients with cirrhosis and to investigate its prognostic value in determination of the 6-month outcome. Methods and material: In this cross-sectional study, patients with liver cirrhosis who were consecutively referred to Imam Reza hospital, tertiary referral center in the northwest of Iran, underwent abdominal paracentesis. The samples were collected for measurement of calprotectin, albumin, total protein, WBCs, and PMNs. RESULTS The mean age of a total of 87 included patients was 56.86 (SD 16.05) years old with over half of the subjects (55.2%) being female. About 28.7% of performed paracenteses tested positive for SBP. Ascitic calprotectin was positively correlated to the PMN counts. Patients with SBP were found to have higher levels of ascites albumin, total protein, and calprotectin. Only 51 individuals survived the 6-month follow-up period and mortality outcomes were significantly related to the levels of aforementioned biochemical markers (p-value <.05). CONCLUSION Alongside with standard PMN counts, calprotectin measurement in the ascitic fluid could be used as an available test for early diagnosis of SBP. Calprotectin can also serve as a valuable prognostic marker in the evaluation of cirrhotic patients.
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Affiliation(s)
- Maryam Nasereslami
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Zhila Khamnian
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Yaghoub Moaddab
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Zahra Jalali
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Hanafy AS, Mohamed MS, Alnagar AA. Ascitic Calprotectin as an early predictor of hepatocellular carcinoma in patients with cirrhotic ascites. J Cancer Res Clin Oncol 2020; 146:3207-3214. [PMID: 32851478 DOI: 10.1007/s00432-020-03363-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Accepted: 08/18/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Calprotectin is a heterodimer formed by S100A8 and S100A9 proteins which are enhanced during hepatic carcinogenesis and the increased expression of both proteins promotes malignant progression of hepatocellular carcinoma. The potential correlation between ascitic Calprotectin and HCC was not studied. METHODS 100 patients were stratified into a case group which enrolled 50 patients with cirrhotic ascites and documented HCC and a control group consisted of 50 patients with cirrhotic ascites without HCC. They were evaluated by liver function tests, abdominal ultrasound and routine ascitic fluid examination including ascetic Calprotectin and results were validated in another group (n = 100). RESULTS Calprotectin level was significantly higher in the HCC group with insignificant difference regarding total cell count, PNLs, ascitic albumin, LDH, CEA and SAAG. It correlated with serum creatinine (r = 0.245, p = 0.014) and number of focal hepatic lesions (r = 0.309, p = 0.002). In the validation group, 28 patients had elevated ascitic Calprotectin of which 21 patients had developed HCC (75%) after a mean period of 3.8 ± 1.54 months. A cut of value 126 ng/ml was accurate to predict HCC in liver cirrhosis with ascites with a sensitivity of 93.3% specificity 94%, AUC 0.950, Youden's J value = 0.873, p = 0.0001. CONCLUSION Ascitic Calprotectin may offer an easy, affordable marker that can predict the early occurrence of HCC.
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Affiliation(s)
- Amr Shaaban Hanafy
- Internal Medicine Department, Hepatogastroenterology Division, Zagazig University, Zagazig, 40 Mostafa Fouad street, 44519, Egypt.
| | - Mohamed Sorour Mohamed
- Internal Medicine Department, Hepatogastroenterology Division, Zagazig University, Zagazig, 40 Mostafa Fouad street, 44519, Egypt
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Abstract
BACKGROUND AND AIMS Recurrence of spontaneous bacterial peritonitis (SBP) is still a matter of debate. We conducted this study to evaluate the probable factors that predict the recurrence of SBP in patients who recovered from the first episode of SBP and the long-term outcomes of SBP recurrence. METHODS One hundred twenty-four patients diagnosed with liver cirrhosis, SBP and did not receive secondary prophylaxis either with norfloxacin or other antibiotics were included in this prospective cohort pilot study. Clinical, biochemical and ascitic fluid analysis parameters were evaluated. Ascitic fluid interferon-γ-induced protein (IP-10), calprotectin, interleukin-6 and tumor necrosis factor-α were measured by ELISA. RESULTS Of these, 76 patients survived with an in-hospital mortality rate of 38.7%. The survivors were classified into two groups according to recurrence and nonrecurrence of SBP and survival time, clinical parameters and cause of death were investigated. Thirty-one participants had one or more attacks of SBP, with a recurrence rate of 40.8% within one-year follow-up. Before discharge, multivariate analysis showed that ascitic IP-10 (≥1220 pg/ml), ascitic calprotectin (≥550 ng/ml), serum albumin (≤2.5 g/dl), nonuse of prophylactic β-blockers and use of proton-pump inhibitors (PPIs) were the independent variables in predicting recurrent SBP. Sepsis-related organ failure was the most common etiology of mortality in the recurrent SBP group within 3 and 6 months. CONCLUSION Increased ascitic calprotectin and IP-10, hypoalbuminemia, nonuse of prophylactic β-blockers and use of PPI were independently associated with increased SBP recurrence rate. Sepsis-related organ failure was the most common etiology of mortality.
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Wu X, Luo J, Huang W, Jia B, Luo T. Role of ascitic endocan levels in the diagnosis of spontaneous bacterial peritonitis in decompensated cirrhosis. Biomarkers 2020; 25:360-366. [PMID: 32364003 DOI: 10.1080/1354750x.2020.1764107] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Objective: To assess the role of ascitic endocan levels in the diagnosis of spontaneous bacterial peritonitis (SBP) in decompensated cirrhosis.Methods: Ascites samples, as well as demographic and laboratory data, were collected at admission from patients with decompensated cirrhosis. Ascitic endocan, tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were measured by ELISA. The influencing factors of SBP, the correlation of ascitic endocan with other inflammatory indicators, and the diagnostic value of ascitic endocan for SBP were analyzed.Results: A total of 167 patients were enrolled, 39 with the SBP group and 128 in the non-SBP group. Ascitic endocan, TNF-α, and IL-6 levels were significantly higher in the SBP group than in the non-SBP group (p < 0.001). Multivariate analysis demonstrated that ascitic endocan was an independent risk factor for SBP [OR = 1.006 (95% CI: 1.002-1.011); p < 0.001]. Endocan was positively correlated with ascites polymorphonuclear leukocytes, TNF-α, and IL-6. ROC curve analysis showed that ascitic endocan had an AUC of 0.805 for the diagnosis of SBP (p < 0.001) and had a sensitivity of 82.1% and specificity of 73.4% when the cut-off value was 295.011 pg/ml.Conclusions: Ascitic endocan level is an independent risk factor and a valuable diagnostic indicator for SBP in decompensated cirrhosis.
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Affiliation(s)
- Xianmei Wu
- Key Laboratory of Infectious and Parasitic Diseases in Chongqing, Department of Infectious Disease, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Junli Luo
- Key Laboratory of Infectious and Parasitic Diseases in Chongqing, Department of Infectious Disease, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Wenxiang Huang
- Key Laboratory of Infectious and Parasitic Diseases in Chongqing, Department of Infectious Disease, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Bei Jia
- Key Laboratory of Infectious and Parasitic Diseases in Chongqing, Department of Infectious Disease, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Tao Luo
- Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Elsadek HM, Elhawari SA, Mokhtar A. A novel serum index for accurate diagnosis of spontaneous bacterial peritonitis in cirrhotic patients without other infections. EGYPTIAN LIVER JOURNAL 2020. [DOI: 10.1186/s43066-020-0021-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Abstract
Background
The accurate non-invasive diagnosis of spontaneous bacterial peritonitis (SBP) in patients with decompensated liver cirrhosis has not been achieved yet. The aim of the study was to obtain an unmistakable diagnosis of SBP using a new simple serum bioscore, made by combined measurement of procalcitonin (PCT), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), which we called the PEC index. This cross-sectional analytic study comprised 178 cirrhotic patients with ascites (60 patients with SBP and 118 patients with sterile ascites), after excluding non-SBP infection, during the period from March 2019 until September 2019. In all participants, serum levels of PCT, ESR, and CRP were measured, and PEC index was calculated [PEC index = PCT × (ESR + CRP)].
Results
Patients with SBP (n = 60) had significantly higher serum PEC index than those with sterile ascites (n = 118) (41.0/31.2–93.0 vs. 9.9/5.9–15.0, P < 0.001). PEC index distinguished culture positive cases significantly (P < 0.001). Using receiver operating characteristic (ROC) statistics, the sensitivity and specificity of PCT, at a cutoff value of 0.590 ng/mL, for SBP diagnosis, were 81.67% and 93.33%, respectively (area under the curve [AUC] = 0.879; 95% confidence interval [CI] 0.809–0.948). The sensitivity and specificity of ESR, at a cutoff value of 27.0 mm/hour, were 73.33% and 61.67%, respectively (AUC = 0.679; 95% CI 0.581–0.776). The sensitivity and specificity of CRP, at a cutoff value of 21.0 mg/L, were 93.33% and 51.67%, respectively (AUC = 0.736; 95% CI 0.639–0.833). While, the sensitivity and specificity of PEC index, at a cutoff value of 20, were highest (98.33% and 96.67%, respectively, AUC = 0.977; 95% CI 0.940–0.996).
Conclusion
Serum PEC index makes an accurate noninvasive diagnosis of SBP, after excluding other infections.
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Milevoj Kopcinovic L, Culej J, Jokic A, Bozovic M, Kocijan I. Laboratory testing of extravascular body fluids: National recommendations on behalf of the Croatian Society of Medical Biochemistry and Laboratory Medicine. Part I - Serous fluids. Biochem Med (Zagreb) 2019; 30:010502. [PMID: 31839720 PMCID: PMC6904973 DOI: 10.11613/bm.2020.010502] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Accepted: 05/20/2019] [Indexed: 12/16/2022] Open
Abstract
Extravascular body fluids (EBF) analysis can provide useful information in the differential diagnosis of conditions that caused their accumulation. Their unique nature and particular requirements accompanying EBF analysis need to be recognized in order to minimize possible negative implications on patient safety. This recommendation was prepared by the members of the Working group for extravascular body fluid samples (WG EBFS). It is designed to address the total testing process and clinical significance of tests used in EBF analysis. The recommendation begins with a chapter addressing validation of methods used in EBF analysis, and continues with specific recommendations for serous fluids analysis. It is organized in sections referring to the preanalytical, analytical and postanalytical phase with specific recommendations presented in boxes. Its main goal is to assist in the attainment of national harmonization of serous fluid analysis and ultimately improve patient safety and healthcare outcomes. This recommendation is intended to all laboratory professionals performing EBF analysis and healthcare professionals involved in EBF collection and processing. Cytological and microbiological evaluations of EBF are beyond the scope of this document.
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Affiliation(s)
- Lara Milevoj Kopcinovic
- Croatian Society of Medical Biochemistry and Laboratory Medicine, Working group for extravascular body fluid samples.,Department of Clinical Chemistry, Sestre milosrdnice University Hospital Center, Zagreb, Croatia
| | - Jelena Culej
- Croatian Society of Medical Biochemistry and Laboratory Medicine, Working group for extravascular body fluid samples.,Department of Clinical Chemistry, Sestre milosrdnice University Hospital Center, Zagreb, Croatia
| | - Anja Jokic
- Croatian Society of Medical Biochemistry and Laboratory Medicine, Working group for extravascular body fluid samples.,Department of Medical Biochemistry, Haematology and Coagulation with Cytology, University Hospital for Infectious Diseases "Dr. Fran Mihaljević", Zagreb, Croatia
| | - Marija Bozovic
- Croatian Society of Medical Biochemistry and Laboratory Medicine, Working group for extravascular body fluid samples.,Department of Clinical Chemistry, Sestre milosrdnice University Hospital Center, Zagreb, Croatia
| | - Irena Kocijan
- Croatian Society of Medical Biochemistry and Laboratory Medicine, Working group for extravascular body fluid samples.,Medical Biochemistry Laboratory, General hospital Varaždin, Varaždin, Croatia
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Abdel-Razik A, Mousa N, Abdel-Aziz M, Elsherbiny W, Zakaria S, Shabana W, Abed S, Elhelaly R, Elzehery R, Eldars W, El-Bendary M. Mansoura simple scoring system for prediction of spontaneous bacterial peritonitis: lesson learnt. Eur J Gastroenterol Hepatol 2019; 31:1017-1024. [PMID: 30694910 DOI: 10.1097/meg.0000000000001364] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND OBJECTIVE Spontaneous bacterial peritonitis (SBP) is a common bacterial infection with life-threatening sequelae in cirrhotic ascites. The purpose of this retrospective cohort study was to recognize the predictors of SBP to build up a noninvasive system to exclude or establish an episode of SBP. PATIENTS AND METHODS Of 1194 consecutive patients with cirrhotic ascites, only 966 patients were enrolled in this study. SBP was diagnosed once polymorphonuclear count was at least 250 cells/mm and/or there was a positive ascitic fluid culture result. Biochemical and clinical parameters were evaluated as predictors of SBP. A scoring system was established in the training group of 682 and validated in a second group of 284 participants. RESULTS The incidence of SBP was 12.3 and 12% in the training and validation groups, respectively. Age of at least 55 years, mean platelet volume (MPV) of at least 8.5 fl, neutrophil-to-lymphocyte ratio (NLR) of at least 2.5, and C-reactive protein (CRP) of at least 40 mg/l were identified as independent predictors of SBP. A scoring system including these four variables (age, MPV, and NLR with 1 point each, whereas CRP with 2 points) achieves a specificity of 98.2% with a positive predictive value for the diagnosis of SBP of 88.1% (score≥4). At a threshold of 1 point, the negative predictive value is 97.5% with a sensitivity of 92.9%. SBP is not associated with a high Model for End-stage Liver Disease score (P=0.135). CONCLUSION The combination of age, MPV, NLR, and CRP in a simple scoring system, Mansoura simple scoring system, supports quick and accurate exclusion or diagnosis of SBP.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Waleed Eldars
- Medical Microbiology and Immunology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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Elshayeb EI, Badr MH, Abdu Elgayed EM, Nor El-dean AS. Serum and ascitic procalcitonin as a marker for early diagnosis of spontaneous bacterial peritonitis. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2019. [DOI: 10.4103/ejim.ejim_74_18] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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30
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Dong R, Wan B, Lin S, Wang M, Huang J, Wu Y, Wu Y, Zhang N, Zhu Y. Procalcitonin and Liver Disease: A Literature Review. J Clin Transl Hepatol 2019; 7:51-55. [PMID: 30944820 PMCID: PMC6441648 DOI: 10.14218/jcth.2018.00012] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2018] [Revised: 09/02/2018] [Accepted: 10/23/2018] [Indexed: 12/23/2022] Open
Abstract
Procalcitonin (PCT) is a widely used biomarker for the diagnosis of bacterial infections. It is produced by various organs and the liver is considered to be the most important site of production. Severe liver dysfunction has been shown to influence PCT levels. Patients with no sources of infection who have liver disease are observed to have increased serum levels of PCT, thereby reducing the diagnostic utility and value within this particular patient subset. Here, we have summarized the relationship between PCT and liver disease, including liver cirrhosis, liver failure, and liver transplantation.
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Affiliation(s)
- Ruolin Dong
- The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Bo Wan
- Liver Research Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Su Lin
- Liver Research Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Mingfang Wang
- Liver Research Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Jiaofeng Huang
- Liver Research Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Yinlian Wu
- Liver Research Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Yilong Wu
- Liver Research Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Nanwen Zhang
- Department of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou, China
| | - Yueyong Zhu
- The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
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Selim FO, El-Deeb NA, Farrag HA, Ahmed AM. Assessment of calprotectin in ascitic fluid as a marker for spontaneous bacterial peritonitis diagnosis in cirrhotic patients. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2019. [DOI: 10.4103/ejim.ejim_17_18] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
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Adjusted Intensive Care Infection Score (ICIS Δ)-A new approach for prediction of ascitic fluid infection in patients with cirrhosis. Dig Liver Dis 2019; 51:104-111. [PMID: 30042037 DOI: 10.1016/j.dld.2018.06.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Revised: 06/07/2018] [Accepted: 06/11/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Early and accurate diagnosis is the key to improving survival in cirrhotic patients with ascitic fluid infection. AIMS To investigate the usefulness of adjusted Intensive Care Infection Score (ICISΔ) for diagnosis of ascites infection in cirrhotic patients. METHODS Cirrhotic patients with ascites (n = 125) were enrolled, and the efficacy of ICIS and ICISΔ for predicting ascites infection was evaluated. ICISΔ was created by using the weighted variation of each ICIS parameter. RESULTS The area under the curves (AUCs) of ICIS for the diagnosis of ascites infection were 0.90 (95% CI: 0.84-0.95), 0.85 (95% CI: 0.79-0.90), and 0.87 (95% CI: 0.81-0.93), for SBP, culture-negative SBP, and combined SBP/culture-negative SBP, respectively. ICIS was optimized and diagnostic accuracy was obviously improved. ICISΔ had high AUCs of 0.99 (95% CI: 0.93-1.00) for SBP, 0.98 (95% CI: 0.83-1.00) for culture-negative SBP, and 0.98 (95% CI: 0.94-1.00) for the combination group. The optimal cutoff was identified as ICISΔ > 2, which had >97.8% sensitivity and 100% specificity for diagnosis of both SBP and culture-negative SBP. The ICISΔ had significantly higher AUCs than PCT and CPR in both groups (P = 0.002-0.008). ICISΔ kinetics could differentiate between SBP and culture-negative SBP patients. From sterile ascites, through culture-negative SBP to SBP, three ICISΔ parameters showed an increasing trend. CONCLUSIONS ICIS and ICISΔ are simple, rapid, accurate and cost-effective methods for the diagnosis of ascites infection in cirrhotic patients.
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Weil D, Heurgue-Berlot A, Monnet E, Chassagne S, Cervoni JP, Feron T, Grandvallet C, Muel E, Bronowicki JP, Thiefin G, Di Martino V, Bardonnet K, Thévenot T. Accuracy of calprotectin using the Quantum Blue Reader for the diagnosis of spontaneous bacterial peritonitis in liver cirrhosis. Hepatol Res 2019; 49:72-81. [PMID: 30084186 DOI: 10.1111/hepr.13239] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2018] [Revised: 07/12/2018] [Accepted: 07/29/2018] [Indexed: 02/08/2023]
Abstract
AIM We aimed to evaluate the accuracy of the dosage of calprotectin in ascitic fluid (AF) using the Quantum Blue assay, for the prompt diagnosis of spontaneous bacterial peritonitis (SBP). METHODS We prospectively collected 236 AF samples from 119 cirrhotic patients hospitalized in two French centers between May 2016 and May 2017. Bloody and chylous/cloudy AF, and secondary peritonitis were excluded. SBP was diagnosed if neutrophils in AF were >250/mm3 using standard cytology. The Quantum Blue Reader selectively measured the calprotectin antigen (MRP8/14) in 12 min within the measurable range from 0.18 to 1.80 μg/mL; values outside this range were registered as 0.17 and 1.81 μg/mL. RESULTS A total of 36 AF were considered as SBP (15.2%). SBP had higher median levels of calprotectin than non-SBP (1.81 vs. 0.25 μg/mL, P < 0.001). Calprotectin levels were positively correlated with neutrophils in AF (r = 0.57, P < 0.001) and C-reactive protein (r = 0.43, P < 0.001), but not with the Child-Pugh and Model for End-Stage Liver Disease scores. The optimal threshold of calprotectin to diagnose SBP was set at 1.51 μg/mL (80th percentile of calprotectin), yielding sensitivity, specificity, and positive and negative predictive values of 86.1%, 92.0%, 65.9%, and 97.3%, respectively. Only one asymptomatic patient with SBP had a low calprotectin level, but a high serum C-reactive protein level that strongly suggested an ongoing infection. We also showed that intraclass correlation coefficients for inter- and intra-observer agreement were excellent, with 0.95 and 0.89, respectively. CONCLUSIONS The dosage of calprotectin in AF using the Quantum Blue assay is a rapid and reliable method of ruling out SBP in hospitalized cirrhotic patients.
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Affiliation(s)
- Delphine Weil
- Department of Hepatology, University Hospital of Besançon, Besançon, France
| | | | - Elisabeth Monnet
- Department of Hepatology, University Hospital of Besançon, Besançon, France
- Unit of Public Health and Epidemiology, CIC INSERM1431, Besançon, France
| | - Sophie Chassagne
- Biology Laboratory, University Hospital Besançon, Besançon, France
| | - Jean-Paul Cervoni
- Department of Hepatology, University Hospital of Besançon, Besançon, France
| | - Thomas Feron
- Department of Hepato-Gastroenterology, University Hospital of Reims, Reims, France
| | | | - Emilie Muel
- Department of Hepatology, University Hospital of Besançon, Besançon, France
| | | | - Gérard Thiefin
- Department of Hepato-Gastroenterology, University Hospital of Reims, Reims, France
| | - Vincent Di Martino
- Department of Hepatology, University Hospital of Besançon, Besançon, France
| | - Karine Bardonnet
- Biology Laboratory, University Hospital Besançon, Besançon, France
| | - Thierry Thévenot
- Department of Hepatology, University Hospital of Besançon, Besançon, France
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Significance of Heparin-Binding Protein and D-dimers in the Early Diagnosis of Spontaneous Bacterial Peritonitis. Mediators Inflamm 2018; 2018:1969108. [PMID: 30363905 PMCID: PMC6186319 DOI: 10.1155/2018/1969108] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2018] [Revised: 08/06/2018] [Accepted: 09/05/2018] [Indexed: 12/18/2022] Open
Abstract
Objectives Ascites and spontaneous bacterial peritonitis (SBP) are among the most important complications of decompensated liver cirrhosis. In clinical practice, new inflammation biomarkers are needed for the early diagnosis of SBP, as well-known biomarkers, such as C-reactive protein (CRP), procalcitonin (PCT), or peripheral blood white blood cell (WBC) count, lack the required specificity and sensitivity. The aim of the study was to evaluate the significance of heparin-binding protein (HBP) in comparison to CRP, PCT, WBC, and D-dimers in the diagnosis of SBP. Design Cross-sectional descriptive single-center study. Setting Department of Infectious and Tropical Diseases and Hepatology, Medical University of Warsaw, Poland. Patients All patients admitted to the aforementioned department with decompensated liver cirrhosis and ascites between February 1, 2016, and June 30, 2017. Intervention Several markers (HBP, CRP, PCT, WBC, and D-dimers) were analysed in blood serum in regard to their potential use in the diagnosis of SBP in patients with decompensated liver cirrhosis and ascites. We correlated the levels of the aforementioned markers with an ascitic fluid polymorphonuclear count using simple linear regression and multiple linear regression. Sensitivities, specificities, and positive and negative predictive values for SBP were calculated for the aforementioned makers of inflammation. Measurements and Main Results A total of 63 patients with decompensated liver cirrhosis and ascites participated in the study. The etiology of liver cirrhosis was varied (HCV: n = 40, HBV: n = 13, HCV/HBV: n = 4, AIH: n = 3, PBC: n = 2, and haemochromatosis: n = 1). After the peritoneal tap, 31 patients were determined to have SBP (defined as an ascitic fluid polymorphonuclear count > 250 cells/μL) and 32 patients had no evidence of SBP on peritoneal tap. A very weak, but statistically significant, correlation of HBP, WBC, and D-dimer levels with the peritoneal fluid polymorphonuclear (PMN) count was observed in the simple regression model, but multivariable analysis using the multiple regression model showed that only D-dimers correlated with peritoneal fluid PMNs independently from other inflammation biomarkers. A D-dimer cutoff value of 1500 ng/mL was determined optimal for ruling out SBP due to high sensitivity (96.8%) and a high negative predictive value (92.9%), although predictably, this marker was not useful for confirming SBP due to low specificity (40.6%) and a low positive predictive value (61.2%). The usefulness of D-dimers was limited by the fact that only 22.2% of the studied patients had D-dimer levels below 1500 ng/mL. HBP and WBC showed little to no predictive value in this study. Conclusions D-dimers < 1500 ng/mL make the diagnosis of SBP unlikely, although the peritoneal tap is still the reference method in such situations. In the studied group, the determination of HBP was of no diagnostic benefit in the diagnosis of SBP.
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Wang H, Li Y, Zhang F, Yang N, Xie N, Mao Y, Li B. Combination of PCT, sNFI and dCHC for the diagnosis of ascites infection in cirrhotic patients. BMC Infect Dis 2018; 18:389. [PMID: 30097024 PMCID: PMC6086035 DOI: 10.1186/s12879-018-3308-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Accepted: 08/03/2018] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND It is difficult to diagnose ascites infection early in cirrhotic patients. The present study was to create and evaluate a new bioscore combined with PCT, sNFI and dCHC in the diagnosis of ascites infection in cirrhotic patients. METHODS Two hundred and fifty-nine consecutive patients were enrolled; of which 51 patients were culture-positive spontaneous bacterial peritonitis (culture-positive SBP) and 58 patients were culture-negative SBP. The efficacy of procalcitonin(PCT), c-reactive protein (CRP), white blood cell (WBC), mean fluorescence intensity of mature neutrophils(sNFI) and difference in hemoglobin concentration between newly formed and mature red blood cells(dCHC) for diagnosing ascites infection was examined. These parameters were used to create a scoring system. The scoring system was analyzed by logistic regression analysis to determine which parameters were statistically different between ascites infection and non-ascites infection patients. Receiver operating characteristic curve (ROC) was used to analyze the diagnostic ability of bioscore for ascites infection. RESULTS In ROC analysis, the area under the curves (AUC) for PCT was 0.852 (95% CI 0.803-0.921, P < 0.001), dCHC 0.837 (95% CI 0.773-0.923, P < 0.001), CRP 0.669 (95% CI 0.610-0.732, P = 0.0624), sNFI 0.838 (95% CI 0.777-0.903, P < 0.001), and WBC 0.624 (95% CI 0.500-0.722, P = 0.0881). Multivariate analysis revealed PCT, dCHC and sNFI to be statistically significant. The combination of these three parameters in the bioscore had an AUC of 0.937 (95% CI 0.901-0.994, P < 0.001). A bioscore of ≥3.40 was considered to be statistically significant in making a positive diagnosis of ascites infection. In different groups of ascites infection, bioscore also shown a high diagnostic value of AUC was 0.947(95% CI 0.882-0.988, P < 0.001) and 0.929 (95% CI 0.869-0.974, P < 0.001) for culture-positive SBP and culture-negative SBP group respectively. CONCLUSION The composite markers of combining PCT, dCHC and sNFI could be a valuable diagnostic score to early diagnose ascites infection in patients with cirrhosis.
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Affiliation(s)
- Han Wang
- Clinical Diagnostic Centre, 302 Military Hospital of China, Beijing, 100039 People’s Republic of China
| | - Yan Li
- Clinical Diagnostic Centre, 302 Military Hospital of China, Beijing, 100039 People’s Republic of China
| | - Fangfang Zhang
- Out-patient department, 302 Military Hospital of China, Beijing, 100039 People’s Republic of China
| | - Ning Yang
- Clinical Diagnostic Centre, 302 Military Hospital of China, Beijing, 100039 People’s Republic of China
| | - Na Xie
- Out-patient department, 302 Military Hospital of China, Beijing, 100039 People’s Republic of China
| | - Yuanli Mao
- Clinical Diagnostic Centre, 302 Military Hospital of China, Beijing, 100039 People’s Republic of China
| | - Boan Li
- Clinical Diagnostic Centre, 302 Military Hospital of China, Beijing, 100039 People’s Republic of China
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Abstract
BACKGROUND AND AIMS The diagnosis of spontaneous bacterial peritonitis (SBP) depends primarily on a polymorphonuclear leukocyte cell count more than 250/mm. This method is invasive, and not diagnostic in all variants of SBP; we aimed to assess serum homocysteine as a precise indicative marker for the diagnosis of all variants of SBP. PATIENTS AND METHODS A total 323 consecutive ascitic patients were registered in this prospective work. Serum and ascitic fluid of homocysteine were evaluated utilizing an enzyme-linked immunosorbent assay. RESULTS Participants were classified into a non-SBP group, including 262 participants and 61 patients with SBP. Serum and ascitic homocysteine were considerably elevated in the SBP group than in the non-SBP group (17.94±7.57 vs. 11.75±5.68 μmol/l; P<0.001 and 14.70±5.45 vs. 9.75±4.55 μmol/l; P<0.001). At a cutoff value of 17.79 μmol/l, serum homocysteine had 89.3% specificity and 95.1% sensitivity for distinguishing SBP (area under the curve: 0.932) and, at a cutoff value of 16.1 μmol/l, ascitic homocysteine had 84.4% specificity and 92.7% sensitivity for distinguishing SBP (area under the curve: 0.901). Both were positively correlated with the polymorphonuclear count, C-reactive protein, Child-Pugh score, and Model For End-Stage Liver Disease score as well as negatively correlated with the protein content in the ascitic fluid and estimated glomerular filtration rate. After SBP therapy, there was a marked reduction in serum and ascitic homocysteine levels. CONCLUSION This study demonstrates that serum and ascitic homocysteine are considerably higher in SBP participants versus non-SBP patients. Serum homocysteine may provide a reliable and noninvasive diagnostic marker for all variants of SBP.
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Heikl AA, El-Nokeety MM, Roshdy E, Mohey A. Ascitic calprotectin as a diagnostic marker for spontaneous bacterial peritonitis in hepatitis C virus cirrhotic Egyptian patients. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2018. [DOI: 10.4103/ejim.ejim_41_17] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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Shizuma T. Spontaneous bacterial and fungal peritonitis in patients with liver cirrhosis: A literature review. World J Hepatol 2018; 10:254-266. [PMID: 29527261 PMCID: PMC5838444 DOI: 10.4254/wjh.v10.i2.254] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Revised: 12/31/2017] [Accepted: 01/24/2018] [Indexed: 02/06/2023] Open
Abstract
Spontaneous bacterial (SBP) and spontaneous fungal peritonitis (SFP) can be a life-threatening infection in patients with liver cirrhosis (LC) and ascites. One of the possible mechanisms of developing SBP is bacterial translocation. Although the number of polymorphonuclear cells in the culture of ascitic fluid is diagnostic for SBP, secondary bacterial peritonitis is necessary to exclude. The severity of underlying liver dysfunction is predictive of developing SBP; moreover, renal impairment and infections caused by multidrug-resistant (MDR) organism are associated with a fatal prognosis of SBP. SBP is treated by antimicrobials, but initial empirical treatment may not succeed because of the presence of MDR organisms, particularly in nosocomial infections. Antibiotic prophylaxis is recommended for patients with LC at a high risk of developing SBP, gastrointestinal bleeding, or a previous episode of SBP, but the increase in the risk of developing an infection caused by MDR organisms is a serious concern globally. Less is known about SFP in patients with LC, but the severity of underlying liver dysfunction may increase the hospital mortality. SFP mortality has been reported to be higher than that of SBP partially because the difficulty of early differentiation between SFP and SBP induces delayed antifungal therapy for SFP.
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Affiliation(s)
- Toru Shizuma
- Department of Physiology, Tokai University School of Medicine, Isehara 2591193, Japan
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Fiore M, Maraolo AE, Leone S, Gentile I, Cuomo A, Schiavone V, Bimonte S, Pace MC, Cascella M. Spontaneous peritonitis in critically ill cirrhotic patients: a diagnostic algorithm for clinicians and future perspectives. Ther Clin Risk Manag 2017; 13:1409-1414. [PMID: 29081656 PMCID: PMC5652902 DOI: 10.2147/tcrm.s144262] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Spontaneous peritonitis (SP) is the most common infection among decompensated end-stage liver disease patients. SP is the infection of ascitic fluid (neutrophil ascitic count ≥250/mL) without an alternative focus of abdominal infection. According to the causative agent, clinicians can make the diagnosis of spontaneous bacterial peritonitis or spontaneous fungal peritonitis. The mortality rate is very high, ranging from one-fifth of the patients with spontaneous bacterial peritonitis to four-fifths of the patients with spontaneous fungal peritonitis. An immediate and accurate diagnosis can improve the outcome in end-stage liver disease patients. The aim of this work is to provide physicians with a practical diagnostic guidance for SP diagnosis according to current evidence, in order to improve the management of cirrhotic patients with infected ascitic fluid.
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Affiliation(s)
- Marco Fiore
- Department of Anaesthesiological, Surgical and Emergency Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Alberto Enrico Maraolo
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, Naples, Italy
| | - Sebastiano Leone
- Division of Infectious Diseases, “San Giuseppe Moscati” Hospital, Avellino, Italy
| | - Ivan Gentile
- Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, Naples, Italy
| | - Arturo Cuomo
- Division of Anesthesia, Department of Anesthesia and Pain Medicine, Istituto Nazionale Tumori – IRCCS – Fondazione G. Pascale, Naples, Italy
| | - Vincenzo Schiavone
- Division of Anesthesia and Intensive Care, Hospital “Pineta Grande”, Castel Volturno, Italy
| | - Sabrina Bimonte
- Division of Anesthesia, Department of Anesthesia and Pain Medicine, Istituto Nazionale Tumori – IRCCS – Fondazione G. Pascale, Naples, Italy
| | - Maria Caterina Pace
- Department of Anaesthesiological, Surgical and Emergency Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Marco Cascella
- Division of Anesthesia, Department of Anesthesia and Pain Medicine, Istituto Nazionale Tumori – IRCCS – Fondazione G. Pascale, Naples, Italy
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Fernandes SR, Santos P, Fatela N, Baldaia C, Tato Marinho R, Proença H, Ramalho F, Velosa J. Ascitic Calprotectin is a Novel and Accurate Marker for Spontaneous Bacterial Peritonitis. J Clin Lab Anal 2016; 30:1139-1145. [PMID: 27184969 DOI: 10.1002/jcla.21994] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2016] [Accepted: 04/13/2016] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Spontaneous bacterial peritonitis (SBP) is a known complication of advanced cirrhosis and presents a high mortality rate. A polymorphonuclear (PMN) cell count >250/μl in the ascitic fluid is the current gold standard for diagnosing SBP. AIM We evaluated the accuracy of a point-of-care test (POCT) for ascitic calprotectin in diagnosing patients with SBP. METHODS Eighty-eight patients admitted with decompensation of liver cirrhosis were studied including 41 patients (46.6%) with SBP. Ascitic calprotectin was measured using a quantitative POCT developed by Bühlmann® . RESULTS Calprotectin levels correlated with PMN cell count and other inflammatory markers and were significantly higher in patients with SBP. An optimal cutoff of calprotectin above 1.57 μg/ml presented high sensitivity (87.8%), specificity (97.9%), and positive (97.3%) and negative (90.2%) predictive values for diagnosing SBP. Using calprotectin selectively in patients with a serum albumin-ascites gradient above 11 g/l further increased the sensitivity and negative predictive values of the test. CONCLUSION Ascitic calprotectin appears to be a reliable method for diagnosing SBP in patients with liver cirrhosis. It may present an alternative to other conventional diagnostic methods.
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Affiliation(s)
- Samuel Raimundo Fernandes
- Serviço de Gastrenterologia e Hepatologia, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisboa, Portugal.
| | - Patrícia Santos
- Serviço de Gastrenterologia e Hepatologia, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisboa, Portugal
| | - Narcisa Fatela
- Serviço de Gastrenterologia e Hepatologia, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisboa, Portugal
| | - Cilénia Baldaia
- Serviço de Gastrenterologia e Hepatologia, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisboa, Portugal
| | - Rui Tato Marinho
- Serviço de Gastrenterologia e Hepatologia, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisboa, Portugal
| | - Helena Proença
- Serviço de Gastrenterologia e Hepatologia, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisboa, Portugal
| | - Fernando Ramalho
- Serviço de Gastrenterologia e Hepatologia, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisboa, Portugal
| | - José Velosa
- Serviço de Gastrenterologia e Hepatologia, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisboa, Portugal
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