Ascitic Calprotectin Research Articles

Study of Ascetic Fluid Lactoferrin and Calprotectin as a Novel Diagnostic Markers in Cirrhotic Patients with Spontaneous Bacterial Peritonitis

Abstract Background Spontaneous bacterial peritonitis (SBP) is a critical infection in patients with liver cirrhosis and ascites, necessitating early diagnosis for effective intervention. The standard diagnostic criterion for SBP is an ascitic fluid polymorphonuclear leukocyte (PMN) count of ≥ 250 cells/mm³. This study explored alternative diagnostic markers for SBP, including high sensitivity C-reactive protein (hsCRP), serum procalcitonin, urinary lipocalin, ascitic lactoferrin, homocysteine, and fecal or ascitic calprotectin. Aim of the Work The aim of this study is to evaluate the diagnostic accuracy of both ascitic fluid calprotectin and lactoferrin in detecting SBP in cirrhotic patients. Patients and Methods The research was conducted at the Hepatology and Gastroenterology Department at Ain Shams University in Egypt from September 2022 to May 2023. Patient data, including demographics, clinical symptoms, laboratory results, and ascitic fluid markers (calprotectin and lactoferrin), were collected and analyzed to assess their diagnostic accuracy for SBP in cirrhotic patients. Results Among the studied population, bleeding, abdominal pain, and fever were significantly more frequent in patients with SBP than those without SBP. Patients with SBP exhibited higher levels of leucocyte count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), bilirubin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), and lower levels of albumin compared to those without SBP. Ascitic fluid parameters, including PMN, calprotectin, and lactoferrin, were significantly higher in patients with SBP. These biomarkers also showed a positive correlation with liver disease severity and were positively correlated with white blood cell count, ESR, and CRP, while calprotectin showed a negative correlation with albumin. At a cut-off point of > 221, ascitic fluid calprotectin demonstrated a sensitivity of 92% and specificity of 96% for predicting SBP, while ascitic fluid lactoferrin, at a cut-off point of > 64.5, had a sensitivity of 92% and specificity of 80% for SBP prediction. Conclusion Both ascitic fluid calprotectin and lactoferrin were significantly elevated in cirrhotic patients with SBP compared to those without SBP. These findings suggest that ascitic fluid calprotectin and lactoferrin can serve as valuable diagnostic tests for screening and diagnosing SBP in patients with liver cirrhosis. Early detection of SBP is crucial for timely intervention and improved patient outcomes.

Ascites fluid calprotectin level is highly accurate in diagnosing spontaneous bacterial peritonitis: a preliminary proof of concept prospective study

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.

Ascitic Calprotectin, as a New Marker of Spontaneous Bacterial Peritonitis (SBP)

Abstract Background Liver cirrhosis results from different mechanisms of live injury that lead to necroinflammation and fibrogenesis; histologically it is characterized by diffuse nodular regeneration surrounded by dense fibrotic septa with subsequent parenchymal extinction and collapse of liver structures, together causing pronounced distortion of hepatic vascular architecture. Objective To evaluate the diagnostic role of ascetic fluid calprotectin in cirrhotic patients with spontaneous bacterial peritonitis before and after treatment. Patients and Methods This study was designed as a case-control study for evaluation of ascitic calprotectin as a diagnostic &amp; prognostic test for spontaneous bacterial peritonitis. The study was conducted on 50 patients attended internal medicine department in El Dmerdash teaching hospital of Ain Shams University during 2018/2019. Results Regarding the ascetic calprotectin after treatment showed decreasing levels correlated with recovery among SBP patients with cut off ≤340 pg/ml had sensitivity 82.5%, specificity 78.0%, PPV 75.0%, NPV 84.8%, accuracy 82.6% in cirrhotic patients with SBP after treatment. Also, the present study found that ascetic calprotectin at cut off value ≤ 780 pg/ml had sensitivity 82.86%, specificity 100%, PPV 100%, NPV 45.5%, accuracy 96.3% in prediction of poor prognosis among SBP cirrhotic patients after treatment. Conclusion The best cut-off is level of ascitic calprotectin ≤ 320 pg/ml which had sensitivity 95%, specificity 90%, PPV 74.5%, NPV 81.8%, accuracy 94.1% in prediction of diagnosis of SBP among cirrhotic patients. The best cut-off level of Ascitic calprotectin ng/mL ≤ 780 pg/ml had sensitivity 82.86%, specificity 100%, PPV 100%, NPV 45.5%, accuracy 96.3% in prediction of poor prognosis among SBP cirrhotic patients after treatment.

Ascitic Calprotectin, as a Potential Diagnostic and Prognostic Marker of Spontaneous Bacterial Peritonitis

Ascitic Calprotectin, as a Potential Diagnostic and Prognostic Marker of Spontaneous Bacterial Peritonitis

Ascitic calprotectin and lactoferrin for detection of spontaneous bacterial peritonitis: a systematic review and meta-analysis.

BackgroundSpontaneous 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.MethodsA 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.ResultsIn 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.ConclusionsThe 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.

An evaluation of ascitic calprotectin for diagnosis of ascitic fluid infection in children with cirrhosis

BackgroundThe 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 methodsIn 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.ResultsThirty-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.ConclusionElevated 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.

Diagnostic Potential of Calprotectin for Spontaneous Bacterial Peritonitis in Patients Withliver Cirrhosis and Ascites.

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.

Ascitic Calprotectin as an early predictor of hepatocellular carcinoma in patients with cirrhotic ascites.

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. 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). 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 ± 1.54months. A cut of value 126ng/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. Ascitic Calprotectin may offer an easy, affordable marker that can predict the early occurrence of HCC.

Diagnostic and prognostic role of ascitic fluid calprotectin level: six-month outcome findings in cirrhotic patients

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.

The diagnostic accuracy of ascitic calprotectin for the early diagnosis of spontaneous bacterial peritonitis: systematic review and meta-analysis.

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.

Recurrence of spontaneous bacterial peritonitis in cirrhosis: novel predictors.

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. 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. 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. 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.

Ascitic calprotectin for the diagnosis of spontaneous bacterial peritonitis: a systematic review and meta-analysis

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.

Ascitic calprotectin as a useful marker in the diagnosis of spontaneous bacterial peritonitis in adults

BackgroundAscitic 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.ResultsThe 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.ConclusionAscitic calprotectin is a useful marker for SBP diagnosis.

COMPARATIVE STUDY OF ASCITIC FLUID AND SERUM LEVELS OF CALPROTECTIN, PROCALCITONIN AND ENDOCAN IN PATIENTS WITH LIVER CIRRHOSIS FOR EARLY DIAGNOSIS AND PREDICTION OF SPONTANEOUS BACTERIAL PERITONITIS

Background: Spontaneous bacterial peritonitis (SBP) is a serious, recurrent, and life-threatening condition developing in cirrhotic patients with a high mortality rate. Its diagnosis is based on ascitic fluid polymorphonuclear leukocytes (PMNs) to be more than 250/μL. Objectives: polymorphonuclear leukocytes (PMNs) to be more than 250/μL. Objective: The aim of the study was to evaluate the ascitic fluid and serum levels of calprotectin, procalcitonin (PCT) and endocan as appropriate markers for predicting and diagnosing SBP. Patients and Methods: This study was conducted on 90 patients with liver cirrhosis: 35 with decompensated cirrhosis and spontaneous bacterial peritonitis, 35 with decompensated cirrhosis without spontaneous bacterial peritonitis and 20 with compensated cirrhosis with no ascites. We evaluate the correlations of calprotectin, procalcitonin and endocan with indicators of infection and inflammation associated with spontaneous bacterial peritonitis in liver cirrhotic patients. Ascitic fluid and serum levels of Calprotectin, procalcitonin, endocan, and polymorphonuclear leukocytes, serum CRP, and blood leukocytes were analyzed. The control group (n = 30) composed of healthy blood donors with normal aminotransferase levels, normal complete blood counts and negative markers for viral hepatitis and HIV. Results: Ascitic fluid and serum levels of Calprotectin, procalcitonin, endocan, and PMNs, serum CRP and blood leukocytes were statistically elevated in cirrhotic patients with SBP than the control group and cirrhotic patients without SBP. There were statistically significant correlations between the existence of SBP with serum calprotectin (r = 0.512), serum procalcitonin (r= 0.370), serum endocan (r = 0.501), ascitic calprotectin (r = 508), ascitic procalcitonin (r = 0.501), ascitic endocan (r = 0.496), ascitic PMNs (r = 0.562), and CRP (r = 0.492), for all P < 0.001. The diagnostic accuracies of calprotectin, endocan, procalcitonin, and PMNs were elevated in progressive disease stage. Ascitic PMNs ≥ 250/mm³ had a sensitivity of 97% and specificity of 94.7%, Serum calprotectin levels ≥ 45 µg/ml had a sensitivity of 96% and specificity of 94%, ascitic calprotectin levels ≥ 0.95 µg/ml had a sensitivity of 95% and specificity of 89.2%, serum endocan levels ≥ 2.03 ng/ml had a sensitivity of 90% and specificity of 83.7%, ascitic procalcitonin levels ≥0.33ng/ml had a sensitivity of 89.9% and specificity of 83.3%, ascitic endocan levels ≥ 0.65 ng/ml had a sensitivity of 88.9% and specificity of 78.5%, and lastly serum procalcitonin levels ≥2.50 ng/ml had a sensitivity of 87.9% and specificity of 76.8% for the diagnosis of SBP in decompensated cirrhotic patients. Conclusion: Ascitic fluid PMNs, serum calprotectin, ascitic calprotectin,serum endocan, ascitic procalcitonin, and serum procalcitonin, could be useful as powerful diagnostic markers to assess the progression of liver disease and early prediction of spontaneous bacterial peritonitis in cirrhotic patients.

Ascitic calprotectin as a diagnostic marker for spontaneous bacterial peritonitis in hepatitis C virus cirrhotic Egyptian patients

BackgroundThe gold standard for the diagnosis of spontaneous bacterial peritonitis (SBP) is a polymorphonuclear leukocyte (PMNL) count of 250/mm3or more. Accurate and early diagnosis of SBP is important to decrease the mortality and complications in patients with cirrhosis.AimsThe aim of this study was to evaluate the accuracy of ascitic fluid calprotectin as a diagnostic marker for the detection of SBP.Patients and methodsSeventy Egyptian patients with liver cirrhosis and ascites were enrolled; these patients were divided into two groups: 50 patients with SBP and 20 patients with no SBP on the basis of an elevated ascitic PMNL count of 250 cells/mm3 or more. Ascitic samples were examined for PMNL count, culture, chemistry, and calprotectin concentrations in all patients.ResultsCalprotectin levels in ascitic fluid were correlated significantly with PMNLs and significantly higher in patients with SBP than non-SBP (P<0.001), with the best cutoff value for the detection of SBP of 783 ng/ml with a sensitivity, a specificity, a positive predictive value and negative predictive value, and an accuracy of 90, 100, 100, 80, and 92.9%, respectively.ConclusionElevated ascitic calprotectin levels in cirrhotic patients are a diagnostic and reliable marker for the detection of SBP and considered a surrogate marker for PMNL.

Ascitic Calprotectin is a Novel and Accurate Marker for Spontaneous Bacterial Peritonitis.

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. We evaluated the accuracy of a point-of-care test (POCT) for ascitic calprotectin in diagnosing patients with SBP. 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® . 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. 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.

Role of Calprotectin in Diagnosis of Spontaneous Bacterial Peritonitis in Cirrhotic Patients with Ascites

Background and study aim: The most common infection in decompensated hepatic patients with cirrhotic ascites is spontaneous bacterial peritonitis (SBP), which occurs in the absence of an evident intra-abdominal source of infection. The aim of this work is to assess the value of calprotectin in ascitic fluid in diagnosis of spontaneous bacterial peritonitis in patients with liver cirrhosis. Patients and Methods: In this cross section study, 80 cirrhotic patients were divided into (group A) 40 patients with non SBP and (group B) 40 patients with SBP, who attended the Hepatology Department Benha University Hospital. All the patients were evaluated by thorough history, clinical examination, laboratory investigations, ultrasonongraphy, diagnostic paracentesis with PMNLs count and Calprotectin which was measured in 1 mL ascetic fluid by ELIZA. Results: Calprotectin was high in SBP group with a highly statistical significant difference in SBP group compared to non SBP group so it can serve as a sensitive and specific diagnostic test for detection of SBP in cirrhotic patients with ascites. The sensitivity of the test was 90% with specificity of 62.5%, PPV of 70.5% and NPV of 86.5% with the cut-off level were 2.98 ng /ml and the area under the curve was 0.88. Conclusion: Ascitic calprotectin reliably predicts PMN count >250/μL, which may prove useful in the diagnosis of SBP, especially with a readily available bedside testing device.

Ascitic Fluid Calprotectin and Serum C-Reactive Protein as Diagnostic Markers for Spontaneous Bacterial Peritonitis

Background and study aim: Spontaneous bacterial peritonitis (SBP) is an important cause of morbidity and mortality in cirrhotic patients with ascites. The diagnosis of SBP is based on PMN leukocyte cell count exceeding 250/μL in ascitic fluid. However, this procedure is time consuming as well as subjective. C-reactive protein (CRP) has been reported to be a reliable predictor of SBP and an index of therapeutic effectiveness in adults. Ascitic fluid calprotectin reliably predicts PMN count >250/μL, which may prove useful in the diagnosis of SBP. This work was planned aiming to evaluate both ascitic fluid calprotectin and serum CRP as accurate diagnostic laboratory markers for detecting SBP. Patients and methods: From 140 patients; only 124 patients with ascites were included in this study. They were divided into SBP group including 70 patients (49 males and 21 females) and non-SBP group of 54 patients (25 males and 29 females). Serum CRP was determined by latex agglutination and ascitic fluid calprotectin was measured using an enzyme-linked immunosorbent assay. Results : Ascitic fluid calprotectin and serum CRP were significantly higher in SBP patients in comparison with the non-SBP group (754.67 ±256.06 vs. 280.77 ±230.97 and 62.4 ±28.39 vs. 9.81 ±8.98) respectively. In addition, both were positively correlated with ascitic fluid proteins and PMN count as well as with each other. At a cutoff value of 270 mg/dl, ascitic fluid calprotectin had 86% specificity and 97.5% sensitivity for detecting SBP [Area under the receiver operating characteristics curve (AUC) = 0.924 with negative and positive predictive values (NPV, PPV) for ascitic calprotectin 96% and 69% respectively. Conclusion : Ascitic fluid calprotectin and serum CRP may be used as accurate and reliable markers for the diagnosis of SBP.

Measurement of calprotectin in ascitic fluid to identify elevated polymorphonuclear cell count

To evaluate the diagnostic capability of calprotectin in ascitic fluid for detecting a polymorphonuclear (PMN) cell count > 250/μL ascites. In this prospective observational study, a total of 130 ascites samples were analysed from 71 consecutive patients referred for paracentesis. Total and differential leukocyte cell counts were determined manually with a Neubauer chamber and gentian-violet stain. Calprotectin was measured in 1 mL ascetic fluid by enzyme-linked immunosorbent assay (ELISA) and a point-of-care (POC) lateral flow assay with the Quantum Blue(®) Reader (Bühlmann Laboratories). All measurements were carried out in a central laboratory by senior personnel blinded to patient history. A PMN count > 250/μL was the primary endpoint of the study. The diagnostic value of ascitic calprotectin measurement was assessed by comparing to the final diagnosis of each patient that had been adjudicated by investigators blinded to calprotectin values. The PMN count was > 250/μL in 19 samples (14.6%) from 15 patients (21.1%) and varied widely among the study population (range 10-19 800/mL and 1-17 820/mL, respectively). Spontaneous bacterial peritonitis (SBP) was the final diagnosis in four patients (5.6%). All patients with PMN ≤ 250/μL had negative bacterial culture. PMN count was elevated in five patients with peritoneal carcinomatosis, three with lymphoma, one with neuroendocrine carcinoma, and two with secondary peritonitis due to abdominal perforation. PMN cell counts correlated with ascitic calprotectin values (Spearman's rho; r = 0.457 for ELISA, r = 0.473 for POC). A considerable range of ascitic calprotectin concentrations was detected by ELISA [median 0.43 μg/mL, interquartile range (IQR) 0.23-1.23 (range 0.10-14.93)] and POC [median 0.38 μg/mL, IQR 0.38-0.56 (range 0.38-13.31)]. Ascitic calprotectin levels were higher in samples with PMN > 250/μL, by both ELISA [median (IQR) 2.48 μg/mL (1.61-3.65) vs 0.10 μg/mL (0.10-0.36), P < 0.001] and POC [2.78 μg/mL (2.05-5.37) vs 0.38 μg/mL (0.38-0.41), P < 0.001]. The area under the receiver operating characteristics curve for identifying an elevated PMN count was 0.977 (95%CI: 0.933 to 0.995) for ELISA and 0.982 (95%CI: 0.942 to 0.997) for POC (P = 0.246 vs ELISA). Using the optimal cut-off value for ELISA (0.63 μg/mL), ascitic calprotectin had 94.8% sensitivity, 89.2% specificity, positive and negative likelihood ratios of 8.76 and 0.06 respectively, positive and negative predictive values of 60.0% and 99.0% respectively, and 90.0% overall accuracy. Using the optimal cut-off value for POC (0.51 μg/mL), the respective values were 100.0%, 84.7%, 6.53, 0.00, 52.8%, 100% and 87.7%. Correlation between ELISA and POC was excellent (r = 0.873, P < 0.001). The mean ± SD of the difference was -0.11 ± 0.48 μg/mL with limits of agreement of + 0.8 μg/mL (95%CI: 0.69 to 0.98) and -1.1 μg/mL (95%CI: -1.19 to -0.91). Ascitic calprotectin reliably predicts PMN count > 250/μL, which may prove useful in the diagnosis of SBP, especially with a readily available bedside testing device.