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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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Cao NH, Ho PT, Bui HH, Vo TD. Non-Invasive Methods for the Prediction of Spontaneous Bacterial Peritonitis in Patients with Cirrhosis. GASTROENTEROLOGY INSIGHTS 2023; 14:170-177. [DOI: 10.3390/gastroent14020013] [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: 07/01/2024] Open
Abstract
Spontaneous bacterial peritonitis (SBP) is a potentially fatal complication in patients with liver cirrhosis. Early diagnosis and prompt treatment of SBP are vital to shorten hospital stays and reduce mortality. According to society guidelines, patients with cirrhosis and ascites who are admitted to the hospital should have diagnostic paracentesis. However, for various reasons, paracentesis may be delayed or not performed. Therefore, recent research has focused on identifying non-invasive parameters useful in SBP prediction which require urgent antibiotic therapy if rapid and secure paracentesis is not possible or there is insufficient experience with this method. In this review, we discuss the non-invasive methods available to predict SBP.
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Affiliation(s)
- Ngoc Huynh Cao
- Department of Internal Medicine, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City 72714, Vietnam
| | - Phat Tan Ho
- Department of Gastroenterology, Cho Ray Hospital, Ho Chi Minh City 72713, Vietnam
| | - Hoang Huu Bui
- Department of Internal Medicine, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City 72714, Vietnam
- Department of Gastroenterology, University Medical Center, Ho Chi Minh City 72714, Vietnam
| | - Thong Duy Vo
- Department of Internal Medicine, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City 72714, Vietnam
- Department of Gastroenterology, Cho Ray Hospital, Ho Chi Minh City 72713, Vietnam
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Evaluating the Benefits of TACE Combined with Lenvatinib Plus PD-1 Inhibitor for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus. Adv Ther 2023; 40:1686-1704. [PMID: 36805422 DOI: 10.1007/s12325-023-02449-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 01/30/2023] [Indexed: 02/23/2023]
Abstract
INTRODUCTION This study evaluated the efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib plus programmed death (PD)-1 inhibitor (TACE-L-P) versus TACE combined with sorafenib plus PD-1 inhibitor (TACE-S-P) in the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). METHODS The clinical data of patients with HCC and PVTT treated with TACE-L-P or TACE-S-P from January 2018 to March 2022 were collected. The Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and modified RECIST (mRECIST) standard were used to evaluate the therapeutic effect. The progression-free survival (PFS) and overall survival (OS) of the two groups were compared. Blood samples were collected before and after treatment to detect the changes of biochemical indicators, and the adverse events (AEs) related to treatment were recorded. RESULTS A total of 165 patients were included in the study, including 80 patients receiving TACE-L-P treatment and 85 patients receiving TACE-S-P. Patients in the TACE-L-P group had longer median OS (21.7 months vs. 15.6 months, P = 0.0027), longer median PFS (6.3 months vs. 3.2 months, P < 0.0001), higher objective response rate (41.25% vs. 30.59%, P = 0.008), and higher disease control rate (86.25% vs. 62.35%, P = 0.008) than those in the TACE-S-P group. Multivariate analysis of the TACE-L-P group showed that VP classification of PVTT, Child-Pugh grade, interleukin-17 (IL-17), vascular endothelial growth factor (VEGF), procalcitonin (PCT), and C-reactive protein (CRP) were independent factors significantly affecting patients' OS (P < 0.05). There was no significant difference in the incidence and severity of AEs between the two groups. CONCLUSION TACE-L-P treatment can improve the survival of patients with HCC and PVTT with an acceptable safety, but higher inflammatory indicators will affect the therapeutic effect.
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Xiang S, Tan J, Tan C, Xu Q, Wen Y, Wang T, Yang C, Zhao W. Establishment and Validation of a Non-Invasive Diagnostic Nomogram to Identify Spontaneous Bacterial Peritonitis in Patients With Decompensated Cirrhosis. Front Med (Lausanne) 2022; 8:797363. [PMID: 35174183 PMCID: PMC8842661 DOI: 10.3389/fmed.2021.797363] [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] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 12/20/2021] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND Spontaneous bacterial peritonitis (SBP) is a common and life-threatening infection in patients with decompensated cirrhosis (DC), and it is accompanied with high mortality and morbidity. However, early diagnosis of spontaneous bacterial peritonitis (SBP) is not possible because of the lack of typical symptoms or the low patient compliance and positivity rate of the ascites puncture test. We aimed to establish and validate a non-invasive diagnostic nomogram to identify SBP in patients with DC. METHOD Data were collected from 4,607 patients with DC from July 2015 to December 2019 in two tertiary hospitals in Chongqing, China (A and B). Patients with DC were divided into the SBP group (995 cases) and the non-SBP group (3,612 cases) depending on whether the patients had SBP during hospitalization. About 70% (2,685 cases) of patients in hospital A were randomly selected as the traindata, and the remaining 30% (1,152 cases) were used as the internal validation set. Patients in hospital B (770 cases) were used as the external validation set. The univariate analysis and least absolute shrinkage and selection operator (LASSO) regression were used to screen variables, and logistic regression was used to determine independent predictors to construct a nomogram to identify patients with SBP. Area under curve (AUC), calibration curve, and dynamic component analysis (DCA) were carried out to determine the effectiveness of the nomogram. RESULT The nomogram was composed of seven variables, namely, mean red blood cell hemoglobin concentration (odds ratio [OR] = 1.010, 95% CI: 1.004-1.016), prothrombin time (OR = 1.038, 95% CI: 1.015-1.063), lymphocyte percentage (OR = 0.955, 95% CI: 0.943-0.967), prealbumin (OR = 0.990, 95% CI: 0.987-0.993), total bilirubin (OR = 1.003 95% CI: 1.002-1.004), abnormal C-reactive protein (CRP) level (OR = 1.395, 95% CI: 1.107-1.755), and abnormal procalcitonin levels (OR = 1.975 95% CI: 1.522-2.556). Good discrimination of the model was observed in the internal and external validation sets (AUC = 0.800 and 0.745, respectively). The calibration curve result indicated that the nomogram was well-calibrated. The DCA curve of the nomogram presented good clinical application ability. CONCLUSION This study identified the independent risk factors of SBP in patients with DC and used them to construct a nomogram, which may provide clinical reference information for the diagnosis of SBP in patients with DC.
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Affiliation(s)
- Shoushu Xiang
- College of Medical Informatics, Chongqing Medical University, Chongqing, China
| | - Juntao Tan
- Department of Medical Administration, People's Hospital of Chongqing Banan District, Chongqing, China
| | - Chao Tan
- Cancer Hospital, Chongqing University, Chongqing, China
| | - Qian Xu
- College of Medical Informatics, Chongqing Medical University, Chongqing, China
| | - Yuanjiu Wen
- Department of General Medicine, Army Medical University (Third Military Medical University), Chongqing, China
| | - Tiantian Wang
- College of Medical Informatics, Chongqing Medical University, Chongqing, China
| | - Chen Yang
- Medical Data Science Academy, Chongqing Medical University, Chongqing, China
| | - Wenlong Zhao
- College of Medical Informatics, Chongqing Medical University, Chongqing, China
- Medical Data Science Academy, Chongqing Medical University, Chongqing, China
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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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NUTRIC and Modified NUTRIC are Accurate Predictors of Outcome in End-Stage Liver Disease: A Validation in Critically Ill Patients with Liver Cirrhosis. Nutrients 2020; 12:nu12072134. [PMID: 32709104 PMCID: PMC7400844 DOI: 10.3390/nu12072134] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 07/10/2020] [Accepted: 07/13/2020] [Indexed: 12/15/2022] Open
Abstract
Malnutrition in critically ill patients with cirrhosis is a frequent but often overlooked complication with high prognostic relevance. The Nutrition Risk in Critically ill (NUTRIC) score and its modified variant (mNUTRIC) were established to assess the nutrition risk of intensive care unit patients. Considering the high mortality of cirrhosis in critically ill patients, this study aims to evaluate the discriminative ability of NUTRIC and mNUTRIC to predict outcome. We performed a retro-prospective evaluation in 150 Caucasian cirrhotic patients admitted to our ICU. Comparative prognostic analyses between NUTRIC and mNUTRIC were assessed in 114 patients. On ICU admission, a large proportion of 65% were classified as high NUTRIC (6-10) and 75% were categorized as high mNUTRIC (5-9). High nutritional risk was linked to disease severity and poor outcome. NUTRIC was moderately superior to mNUTRIC in prediction of 28-day mortality (area under curve 0.806 vs. 0.788) as well as 3-month mortality (area under curve 0.839 vs. 0.819). We found a significant association of NUTRIC and mNUTRIC with MELD, CHILD, renal function, interleukin 6 and albumin, but not with body mass index. NUTRIC and mNUTRIC are characterized by high prognostic accuracy in critically ill patients with cirrhosis. NUTRIC revealed a moderate advantage in prognostic ability compared to mNUTRIC.
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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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Ponziani FR, Zocco MA, Cerrito L, Gasbarrini A, Pompili M. Bacterial translocation in patients with liver cirrhosis: physiology, clinical consequences, and practical implications. Expert Rev Gastroenterol Hepatol 2018; 12:641-656. [PMID: 29806487 DOI: 10.1080/17474124.2018.1481747] [Citation(s) in RCA: 87] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Accepted: 05/24/2018] [Indexed: 02/07/2023]
Abstract
The gut liver axis is an operative unit that works to protect the human body against potentially harmful substances and microorganisms, maintaining the homeostasis of the immune system. Liver cirrhosis profoundly alters this complex system. The intestine becomes more permeable allowing the translocation of bacteria, bacterial products and fragments into the portal circulation, triggering an abnormal local and systemic inflammatory response and a condition of perpetual immunologic alarm. This immune-inflammatory disorder related to dysbiosis is involved in the development of liver damage and liver cirrhosis complications and increases intestinal permeability in a vicious circle. Areas covered: The most relevant studies on bacterial translocation, the mechanism of intestinal barrier dysfunction and its consequences in patients with liver cirrhosis have been revised through a PubMed search. Data have been discussed with particular regard to their significance in clinical practice. Expert commentary: The assessment of bacterial translocation and intestinal permeability is not currently used in clinical practice but may be useful to stratify patients' prognosis.
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Affiliation(s)
- Francesca Romana Ponziani
- a Internal Medicine, Gastroenterology and Hepatology , Fondazione Agostino Gemelli Hospital , Rome , Italy
| | - Maria Assunta Zocco
- a Internal Medicine, Gastroenterology and Hepatology , Fondazione Agostino Gemelli Hospital , Rome , Italy
| | - Lucia Cerrito
- a Internal Medicine, Gastroenterology and Hepatology , Fondazione Agostino Gemelli Hospital , Rome , Italy
| | - Antonio Gasbarrini
- a Internal Medicine, Gastroenterology and Hepatology , Fondazione Agostino Gemelli Hospital , Rome , Italy
| | - Maurizio Pompili
- a Internal Medicine, Gastroenterology and Hepatology , Fondazione Agostino Gemelli Hospital , Rome , Italy
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Predictive Value of Procalcitonin for Bacterial Infection after Transarterial Chemoembolization or Radiofrequency Ablation for Hepatocellular Carcinoma. DISEASE MARKERS 2018; 2018:9120878. [PMID: 29849829 PMCID: PMC5932480 DOI: 10.1155/2018/9120878] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/19/2018] [Accepted: 04/04/2018] [Indexed: 02/07/2023]
Abstract
This prospective observational study aimed at investigating the role of procalcitonin (PCT) in diagnosing bacterial infection and guiding antibiotic therapy for hepatocellular carcinoma (HCC) patients with fever after transarterial chemoembolization (TACE) and/or radiofrequency ablation (RFA). Ninety-seven cases (84 patients) were enrolled. Serum PCT, C-reactive protein (CRP), and white blood cell (WBC) counts were measured on the day of fever onset (day 0) and days 1, 3, 5, and 7 of fever. Empirical antibiotics were initiated only if PCT was ≥0.5 ng/mL or specific infection foci were suspected. An infectious cause was found in nine cases. PCT on day 0 of fever was significantly higher in patients with bacterial infection than in those without infection (P = 0.035). The area under the receiver operating characteristic curve for PCT was 0.715 (95% confidence interval, 0.538–0.892) and was higher than that for CRP (0.598 (0.368–0.828)) or WBC counts (0.502 (0.307–0.697)). In patients undergoing TACE and/or RFA, a significantly lower number of antibiotics were prescribed during the study period than during the prestudy period (P < 0.001). In conclusion, PCT might be a biomarker for diagnosing infection and guiding antibiotic treatment to reduce unnecessary antibiotic use in patients with fever after TACE and/or RFA.
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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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Choi JJ, McCarthy MW. Novel applications for serum procalcitonin testing in clinical practice. Expert Rev Mol Diagn 2017; 18:27-34. [PMID: 29148856 DOI: 10.1080/14737159.2018.1407244] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
INTRODUCTION Procalcitonin has emerged as a reliable marker of acute bacterial infection in hospitalized patients and the assay has recently been incorporated into several clinical algorithms to reduce antimicrobial overuse, but its use in patients with end-organ dysfunction is controversial. Areas covered: In this review, the authors examine what is known about procalcitonin testing in patients with organ dysfunction, including those with end-stage renal disease, congestive heart failure, chronic obstructive pulmonary disease, and cirrhosis, and explore how the assay is now being used in the management of non-infectious diseases. Expert commentary: Procalcitonin holds tremendous promise to identify a diverse set of medical conditions beyond those associated with acute bacterial infection, including post-surgical anastomotic leaks, acute kidney injury, and complications after intracerebral hemorrhage. The authors review recent studies examining procalcitonin in these areas and explore how the assay might be used to guide diagnosis and prognosis of non-infectious diseases in the near future.
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Affiliation(s)
- Justin J Choi
- a Division of General Internal Medicine , Weill Cornell Medical College, New York-Presbyterian Hospital , New York , NY , USA
| | - Matthew W McCarthy
- a Division of General Internal Medicine , Weill Cornell Medical College, New York-Presbyterian Hospital , New York , NY , USA
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Alexopoulou A, Agiasotelli D, Vasilieva LE, Dourakis SP. Bacterial translocation markers in liver cirrhosis. Ann Gastroenterol 2017; 30:486-497. [PMID: 28845103 PMCID: PMC5566768 DOI: 10.20524/aog.2017.0178] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2017] [Accepted: 06/19/2017] [Indexed: 12/12/2022] Open
Abstract
Bacterial translocation (BT) is an important mechanism in the development of infection in liver cirrhosis. The migration and colonization of bacteria and/or bacterial products from the bowel to mesenteric lymph nodes is a controlled process in healthy persons. Increased intestinal permeability, bacterial overgrowth and defect of gut-associated lymphatic tissue promote impaired BT in cirrhotics. We reviewed the reports on markers used for the evaluation of BT published between 1987 and 2016. We focused on the clinical consequences of BT in cirrhosis, as indicated by the values of the BT markers. Patients with cirrhosis are reported to have elevated levels of surrogate markers associated with BT compared with controls. The most widely used BT parameters are C-reactive protein, procalcitonin, bacterial DNA, endotoxin or lipopolysaccharide, lipopolysaccharide binding protein, calprotectin, and bactericidal/permeability increasing protein. High levels of these factors in serum and/or ascitic fluid in humans may be associated with advanced liver disease, hemodynamic instability, high levels of proinflammatory cytokines, susceptibility to the development of severe or recurrent infections, acute-on-chronic liver failure, hepatic encephalopathy, hepatorenal syndrome and poor prognosis during follow up. In conclusion, high levels of BT markers are associated with a high inflammatory response, increased complications of liver cirrhosis and occasionally high fatality rates.
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Affiliation(s)
- Alexandra Alexopoulou
- 2 Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, "Hippokration" Hospital, Athens, Greece
| | - Danai Agiasotelli
- 2 Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, "Hippokration" Hospital, Athens, Greece
| | - Larisa E Vasilieva
- 2 Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, "Hippokration" Hospital, Athens, Greece
| | - Spyros P Dourakis
- 2 Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, "Hippokration" Hospital, Athens, Greece
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Papp M, Tornai T, Vitalis Z, Tornai I, Tornai D, Dinya T, Sumegi A, Antal-Szalmas P. Presepsin teardown - pitfalls of biomarkers in the diagnosis and prognosis of bacterial infection in cirrhosis. World J Gastroenterol 2016; 22:9172-9185. [PMID: 27895404 PMCID: PMC5107598 DOI: 10.3748/wjg.v22.i41.9172] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2016] [Revised: 08/26/2016] [Accepted: 09/28/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the diagnostic and prognostic value of presepsin in cirrhosis-associated bacterial infections.
METHODS Two hundred and sixteen patients with cirrhosis were enrolled. At admission, the presence of bacterial infections and level of plasma presepsin, serum C-reactive protein (CRP) and procalcitonin (PCT) were evaluated. Patients were followed for three months to assess the possible association between presepsin level and short-term mortality.
RESULTS Present 34.7 of patients had bacterial infection. Presepsin levels were significantly higher in patients with infection than without (median, 1002 pg/mL vs 477 pg/mL, P < 0.001), increasing with the severity of infection [organ failure (OF): Yes vs No, 2358 pg/mL vs 710 pg/mL, P < 0.001]. Diagnostic accuracy of presepsin for severe infections was similar to PCT and superior to CRP (AUC-ROC: 0.85, 0.85 and 0.66, respectively, P = NS for presepsin vs PCT and P < 0.01 for presepsin vs CRP). At the optimal cut-off value of presepsin > 1206 pg/mL sensitivity, specificity, positive predictive values and negative predictive values were as follows: 87.5%, 74.5%, 61.8% and 92.7%. The accuracy of presepsin, however, decreased in advanced stage of the disease or in the presence of renal failure, most probably because of the significantly elevated presepsin levels in non-infected patients. 28-d mortality rate was higher among patients with > 1277 pg/mL compared to those with ≤ 1277 pg/mL (46.9% vs 11.6%, P < 0.001). In a binary logistic regression analysis, however, only PCT (OR = 1.81, 95%CI: 1.09-3.01, P = 0.022) but neither presepsin nor CRP were independent risk factor for 28-d mortality after adjusting with MELD score and leukocyte count.
CONCLUSION Presepsin is a valuable new biomarker for defining severe infections in cirrhosis, proving same efficacy as PCT. However, it is not a useful marker of short-term mortality.
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Wu Y, Wang M, Zhu Y, Lin S. Serum interleukin-6 in the diagnosis of bacterial infection in cirrhotic patients: A meta-analysis. Medicine (Baltimore) 2016; 95:e5127. [PMID: 27741137 PMCID: PMC5072964 DOI: 10.1097/md.0000000000005127] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2016] [Revised: 07/27/2016] [Accepted: 09/22/2016] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND The diagnostic accuracy of interleukin-6 (IL-6) in predicting bacterial infection in cirrhotic patients remains unclear. The aim of this meta-analysis is to explore the potential diagnostic value of IL-6 in cirrhotic patients. METHODS We systematically searched PubMed, Embase (via OvidSP), Web of Science, the Cochrane Library, and Scopus for studies published from inception to October 2015. Studies were enrolled if they included assessment of the accuracy of IL-6 in the diagnosis of bacterial infection in cirrhotic patients and provided sufficient data to construct a 2 × 2 contingency table. RESULTS Totally, 535 studies were searched in the initial database and finally 6 studies involving 741 patients were included for the final analysis. The pooled sensitivity, specificity and diagnostic odds ratio were 0.85 (95% confidence interval [CI], 0.64-0.94), 0.91 (95% CI, 0.80-0.96) and 52.89 (95% CI, 15.21-183.86), respectively. The pooled positive likelihood ratio was 8.99 (95% CI, 4.13-19.55) and the pooled negative likelihood ratio was 0.17 (95% CI, 0.07-0.43). The area under the receiver operating characteristic curve was 0.94 (95% CI, 0.92-0.96). CONCLUSION This meta-analysis suggests IL-6 has a high diagnostic value for the differentiation of bacterial infection in patients with cirrhosis.
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Affiliation(s)
| | | | | | - Su Lin
- Liver Research Center, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
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15
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Usefulness of procalcitonin for diagnosing infection in critically ill patients with liver cirrhosis. ACTA ACUST UNITED AC 2016. [DOI: 10.1016/j.medine.2015.02.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
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Yang Y, Li L, Qu C, Zeng B, Liang S, Luo Z, Wang X, Zhong C. Diagnostic Accuracy of Serum Procalcitonin for Spontaneous Bacterial Peritonitis Due to End-stage Liver Disease: A Meta-analysis. Medicine (Baltimore) 2015; 94:e2077. [PMID: 26656333 PMCID: PMC5008478 DOI: 10.1097/md.0000000000002077] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Early diagnosis and prompt treatment of spontaneous bacterial peritonitis (SBP) due to end-stage liver disease is vital to shorten hospital stays and reduce mortality. Many studies have explored the potential usefulness of serum procalcitonin (PCT) in predicting SBP. The aim of this study is to evaluate the overall diagnostic accuracy of PCT levels for identifying SBP due to end-stage liver disease.After performing a systematic search of the Medline, Embase, and Cochrane databases for studies that evaluated the diagnostic role of PCT for SBP, sensitivity, specificity, and other measures of accuracy of PCT concentrations in serum for SBP diagnosis were pooled using random-effects models. A summary receiver operating characteristic curve was used to summarize overall test performance.Seven publications met the inclusion criteria covering 742 episodes of suspected SBP along with 339 confirmed cases. The summary estimates for serum PCT in the diagnosis of SBP attributable to end-stage liver disease were: sensitivity 0.82 (95% CI 0.79-0.87), specificity 0.86 (95% CI 0.82-0.89), positive likelihood ratio 4.94 (95% CI 2.28-10.70), negative likelihood ratio 0.22 (95% CI 0.10-0.52), and diagnostic OR 22.55 (95% CI 7.01-108.30). The area under the curve was 0.92. There was evidence of significant heterogeneity but no evidence of publication bias.Serum PCT is a relatively sensitive and specific test for the identification of SBP. However, due to the limited high-quality studies available, medical decisions should be carefully made in the context of both PCT test results and other clinical findings.
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Affiliation(s)
- Yongtao Yang
- From the Department of Gastroenterology, The 306th Hospital of PLA, Chaoyang District, Beijing, China
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Rule JA, Hynan LS, Attar N, Sanders C, Korzun WJ, Lee WM. Procalcitonin Identifies Cell Injury, Not Bacterial Infection, in Acute Liver Failure. PLoS One 2015; 10:e0138566. [PMID: 26393924 PMCID: PMC4579124 DOI: 10.1371/journal.pone.0138566] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2015] [Accepted: 09/01/2015] [Indexed: 12/22/2022] Open
Abstract
Background Because acute liver failure (ALF) patients share many clinical features with severe sepsis and septic shock, identifying bacterial infection clinically in ALF patients is challenging. Procalcitonin (PCT) has proven to be a useful marker in detecting bacterial infection. We sought to determine whether PCT discriminated between presence and absence of infection in patients with ALF. Method Retrospective analysis of data and samples of 115 ALF patients from the United States Acute Liver Failure Study Group randomly selected from 1863 patients were classified for disease severity and ALF etiology. Twenty uninfected chronic liver disease (CLD) subjects served as controls. Results Procalcitonin concentrations in most samples were elevated, with median values for all ALF groups near or above a 2.0 ng/mL cut-off that generally indicates severe sepsis. While PCT concentrations increased somewhat with apparent liver injury severity, there were no differences in PCT levels between the pre-defined severity groups–non-SIRS and SIRS groups with no documented infections and Severe Sepsis and Septic Shock groups with documented infections, (p = 0.169). PCT values from CLD patients differed from all ALF groups (median CLD PCT value 0.104 ng/mL, (p ≤0.001)). Subjects with acetaminophen (APAP) toxicity, many without evidence of infection, demonstrated median PCT >2.0 ng/mL, regardless of SIRS features, while some culture positive subjects had PCT values <2.0 ng/mL. Summary/Conclusions While PCT appears to be a robust assay for detecting bacterial infection in the general population, there was poor discrimination between ALF patients with or without bacterial infection presumably because of the massive inflammation observed. Severe hepatocyte necrosis with inflammation results in elevated PCT levels, rendering this biomarker unreliable in the ALF setting.
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Affiliation(s)
- Jody A Rule
- Department of Internal Medicine, Division of Digestive Diseases, UT Southwestern Medical Center, Dallas, Texas, United States of America; Department of Clinical Laboratory Sciences, School of Allied Health, Virginia Commonwealth University, Richmond, Virginia, United States of America
| | - Linda S Hynan
- Department of Clinical Sciences and Department of Psychiatry, Division of Biostatistics, UT Southwestern Medical Center, Dallas, Texas, United States of America
| | - Nahid Attar
- Department of Internal Medicine, Division of Digestive Diseases, UT Southwestern Medical Center, Dallas, Texas, United States of America
| | - Corron Sanders
- Department of Internal Medicine, Division of Digestive Diseases, UT Southwestern Medical Center, Dallas, Texas, United States of America
| | - William J Korzun
- Department of Clinical Laboratory Sciences, School of Allied Health, Virginia Commonwealth University, Richmond, Virginia, United States of America
| | - William M Lee
- Department of Internal Medicine, Division of Digestive Diseases, UT Southwestern Medical Center, Dallas, Texas, United States of America
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Koutsounas I, Kaltsa G, Siakavellas SI, Bamias G. Markers of bacterial translocation in end-stage liver disease. World J Hepatol 2015; 7:2264-2273. [PMID: 26380651 PMCID: PMC4568487 DOI: 10.4254/wjh.v7.i20.2264] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Revised: 08/13/2015] [Accepted: 08/30/2015] [Indexed: 02/06/2023] Open
Abstract
Bacterial translocation (BT) refers to the passage of viable bacteria or bacterial products from the intestinal lumen, through the intestinal epithelium, into the systemic circulation and extraintestinal locations. The three principal mechanisms that are thought to be involved in BT include bacterial overgrowth, disruption of the gut mucosal barrier and an impaired host defence. BT is commonly observed in liver cirrhosis and has been shown to play an important role in the pathogenesis of the complications of end stage liver disease, including infections as well as hepatic encephalopathy and hepatorenal syndrome. Due to the importance of BT in the natural history of cirrhosis, there is intense interest for the discovery of biomarkers of BT. To date, several such candidates have been proposed, which include bacterial DNA, soluble CD14, lipopolysaccharides endotoxin, lipopolysaccharide-binding protein, calprotectin and procalcitonin. Studies on the association of these markers with BT have demonstrated not only promising data but, oftentimes, contradictory results. As a consequence, currently, there is no optimal marker that may be used in clinical practice as a surrogate for the presence of BT.
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Affiliation(s)
- Ioannis Koutsounas
- Ioannis Koutsounas, Garyfallia Kaltsa, Spyros I Siakavellas, Giorgos Bamias, Academic Department of Gastroenterology, Ethnikon and Kapodistriakon University, School of Medical Sciences, Laikon General Hospital, 11527 Athens, Greece
| | - Garyfallia Kaltsa
- Ioannis Koutsounas, Garyfallia Kaltsa, Spyros I Siakavellas, Giorgos Bamias, Academic Department of Gastroenterology, Ethnikon and Kapodistriakon University, School of Medical Sciences, Laikon General Hospital, 11527 Athens, Greece
| | - Spyros I Siakavellas
- Ioannis Koutsounas, Garyfallia Kaltsa, Spyros I Siakavellas, Giorgos Bamias, Academic Department of Gastroenterology, Ethnikon and Kapodistriakon University, School of Medical Sciences, Laikon General Hospital, 11527 Athens, Greece
| | - Giorgos Bamias
- Ioannis Koutsounas, Garyfallia Kaltsa, Spyros I Siakavellas, Giorgos Bamias, Academic Department of Gastroenterology, Ethnikon and Kapodistriakon University, School of Medical Sciences, Laikon General Hospital, 11527 Athens, Greece
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Sepsis: From Pathophysiology to Individualized Patient Care. J Immunol Res 2015; 2015:510436. [PMID: 26258150 PMCID: PMC4518174 DOI: 10.1155/2015/510436] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2015] [Revised: 06/24/2015] [Accepted: 07/02/2015] [Indexed: 12/13/2022] Open
Abstract
Sepsis has become a major health economic issue, with more patients dying in hospitals due to sepsis related complications compared to breast and colorectal cancer together. Despite extensive research in order to improve outcome in sepsis over the last few decades, results of large multicenter studies were by-and-large very disappointing. This fiasco can be explained by several factors, but one of the most important reasons is the uncertain definition of sepsis resulting in very heterogeneous patient populations, and the lack of understanding of pathophysiology, which is mainly based on the imbalance in the host-immune response. However, this heroic research work has not been in vain. Putting the results of positive and negative studies into context, we can now approach sepsis in a different concept, which may lead us to new perspectives in diagnostics and treatment. While decision making based on conventional sepsis definitions can inevitably lead to false judgment due to the heterogeneity of patients, new concepts based on currently gained knowledge in immunology may help to tailor assessment and treatment of these patients to their actual needs. Summarizing where we stand at present and what the future may hold are the purpose of this review.
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Villarreal E, Vacacela K, Gordon M, Calabuig C, Alonso R, Ruiz J, Kot P, Babiloni D, Ramírez P. [Usefulness of procalcitonin for diagnosing infection in critically ill patients with liver cirrhosis]. Med Intensiva 2015; 40:84-9. [PMID: 25843699 DOI: 10.1016/j.medin.2015.02.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2014] [Revised: 01/05/2015] [Accepted: 02/08/2015] [Indexed: 12/12/2022]
Abstract
OBJECTIVE To evaluate the usefulness of procalcitonin (PCT) for diagnosing infection in patients with liver cirrhosis admitted to an Intensive Care Unit. DESIGN A retrospective study was carried out. SCOPE Intensive Care Unit. Versatile, twenty-four beds. Participants Patients with liver cirrhosis admitted to our Intensive Care Unit in the last four years with suspected infection and measurement of PCT. RESULTS Among the 255 patients with cirrhosis admitted to our unit, PCT was determined for the differential diagnosis of infection in 69 cases (27%). Three patients were excluded from analysis due to a lack of clinical data. The average stay was 10.6 ± 9.2 days, with a mortality rate of 65%. The origin of cirrhosis was mainly viral (57%) or alcoholic (37%). The Child-Pugh and MELD scores were 9.5 ± 2 and 23 ± 8, respectively. Infection was diagnosed in 54 patients (82%). The most common infection was pneumonia (72%), followed by intraabdominal infections (18%) and bacteremia (5%). In patients without infection, the median PCT concentration was 0.57 ng/ml (range 0.28 to 1.14) versus 2.99 (1.31 to 9.4) in those with infection (p<.001). Diagnostic capacity was maintained in patients with intraabdominal infections. The diagnostic cutoff point was set at 0.8 ng/ml (sensitivity 83%, specificity 75%, AUC 0.82 [0.702-0.93]). CONCLUSIONS In patients with liver cirrhosis, PCT is useful for identifying bacterial infections, including intraabdominal processes.
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Affiliation(s)
- E Villarreal
- Servicio de Medicina Intensiva, Hospital Universitario y Politécnico La Fe, Valencia, España
| | - K Vacacela
- Servicio de Medicina Intensiva, Hospital Universitario y Politécnico La Fe, Valencia, España
| | - M Gordon
- Servicio de Medicina Intensiva, Hospital Universitario y Politécnico La Fe, Valencia, España
| | - C Calabuig
- Servicio de Medicina Intensiva, Hospital Universitario y Politécnico La Fe, Valencia, España
| | - R Alonso
- Servicio de Medicina Intensiva, Hospital Universitario y Politécnico La Fe, Valencia, España
| | - J Ruiz
- Servicio de Medicina Intensiva, Hospital Universitario y Politécnico La Fe, Valencia, España
| | - P Kot
- Servicio de Medicina Intensiva, Hospital Universitario y Politécnico La Fe, Valencia, España
| | - D Babiloni
- Servicio de Medicina Intensiva, Hospital Universitario y Politécnico La Fe, Valencia, España
| | - P Ramírez
- Servicio de Medicina Intensiva, Hospital Universitario y Politécnico La Fe, Valencia, España.
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21
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Cai ZH, Fan CL, Zheng JF, Zhang X, Zhao WM, Li B, Li L, Dong PL, Ding HG. Measurement of serum procalcitonin levels for the early diagnosis of spontaneous bacterial peritonitis in patients with decompensated liver cirrhosis. BMC Infect Dis 2015; 15:55. [PMID: 25887691 PMCID: PMC4332920 DOI: 10.1186/s12879-015-0776-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2014] [Accepted: 01/21/2015] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND It is difficult to diagnose spontaneous bacterial peritonitis (SBP) early in decompensated liver cirrhotic ascites patients (DCPs). The aim of the study was to measure serum procalcitonin (PCT) levels and peripheral blood leukocyte/platelet (WBC/PLT) ratios to obtain an early diagnostic indication of SBP in DCPs. METHODS Our cohort of 129 patients included 112 DCPs (94 of whom had infections) and 17 cases with compensated cirrhosis as controls. Bacterial cultures, ascitic fluid (AF) leukocyte and peripheral WBC/PLT counts, and serum PCT measurements at admission were carried out prior to the use of antibiotics. Receiver operating characteristic (ROC) curves were generated to test the accuracies and cut-off values for different inflammatory markers. RESULTS Among the 94 infected patients, 66 tested positive by bacterial culture, for which the positivity of blood, ascites and other secretions were 25.8%, 30.3% and 43.9%, respectively. Lung infection, SBP and unknown sites of infection accounted for 8.5%, 64.9% and 26.6% of the cases, respectively. Serum PCT levels (3.02 ± 3.30 ng/mL) in DCPs with infections were significantly higher than those in control patients (0.15 ± 0.08 ng/mL); p < 0.05. We used PCT ≥0.5 ng/mL as a cut-off value to diagnose infections, for which the sensitivity and specificity was 92.5% and 77.1%. The area under the curve (AUC) was 0.89 (95% confidence interval: 0.84-0.91). The sensitivity and specificity were 62.8% and 94.2% for the diagnosis of infections, and were 68.8% and 94.2% for the diagnosis of SBP in DCPs when PCT ≥2 ng/mL was used as a cut-off value. For the combined PCT and WBC/PLT measurements, the sensitivity was 76.8% and 83.6% for the diagnosis of infections or SBP in DCPs, respectively. CONCLUSION Serum PCT levels alone or in combination with WBC/PLT measurements seem to provide a satisfactory early diagnostic biomarker in DCPs with infections, especially for patients with SBP.
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Affiliation(s)
- Zhao-Hua Cai
- Department of Gastroenterology and Hepatology, Beijing You'an Hospital affiliated to Capital Medical University, Beijing, Fengtai District, 100069, China.
- Department of Internal Medicine, The Second Hospital Beijing, Beijing, Xicheng District, 100031, China.
| | - Chun-Lei Fan
- Department of Gastroenterology and Hepatology, Beijing You'an Hospital affiliated to Capital Medical University, Beijing, Fengtai District, 100069, China.
| | - Jun-Fu Zheng
- Department of Gastroenterology and Hepatology, Beijing You'an Hospital affiliated to Capital Medical University, Beijing, Fengtai District, 100069, China.
| | - Xin Zhang
- Department of Gastroenterology and Hepatology, Beijing You'an Hospital affiliated to Capital Medical University, Beijing, Fengtai District, 100069, China.
| | - Wen-Min Zhao
- Department of Gastroenterology and Hepatology, Beijing You'an Hospital affiliated to Capital Medical University, Beijing, Fengtai District, 100069, China.
| | - Bing Li
- Department of Gastroenterology and Hepatology, Beijing You'an Hospital affiliated to Capital Medical University, Beijing, Fengtai District, 100069, China.
| | - Lei Li
- Department of Gastroenterology and Hepatology, Beijing You'an Hospital affiliated to Capital Medical University, Beijing, Fengtai District, 100069, China.
| | - Pei-Ling Dong
- Department of Gastroenterology and Hepatology, Beijing You'an Hospital affiliated to Capital Medical University, Beijing, Fengtai District, 100069, China.
| | - Hui-Guo Ding
- Department of Gastroenterology and Hepatology, Beijing You'an Hospital affiliated to Capital Medical University, Beijing, Fengtai District, 100069, China.
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Marciano S, Haddad L, Martínez AP, Posadas ML, Piñero F, Mora GJ, Guerrero LN, Ridruejo E, Mandó OG, Giunta DH, Gadano AC. Ultra-sensitive procalcitonin may help rule out bacterial infections in patients with cirrhosis. Ann Hepatol 2014; 13:541-547. [PMID: 25152987 DOI: 10.1016/s1665-2681(19)31254-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
Abstract
BACKGROUND Bacterial infections are frequent complications in patients with cirrhosis. Since they are associated with poor outcomes, antibiotics are frequently over-prescribed. Surrogate markers of bacterial infections, like procalcitonin, are needed to better discriminate between infected and not infected patients. AIMS To evaluated the diagnostic accuracy of an ultra-sensitive procalcitonin assay for the diagnosis of bacterial infections in patients with cirrhosis. MATERIAL AND METHODS In a single-center prospective study, we determined the basal levels of procalcitonin in 106 episodes of admissions to the emergency department in 84 cirrhotic patients. Patients were classified as infected or not infected by two independent hepatologists blinded to the procalcitonin result. RESULTS The prevalence of bacterial infection was 28% (29 episodes). The median procalcitonin was significantly higher in the infected group than in the not infected group (0.45 vs. 0.061 ng/mL, p < 0.001). The diagnostic accuracy of procalcitonin for bacterial infection estimated by the ROC curve was 0.95 (CI: 95%, 0.91-0.99). When selecting a cutoff value of 0.098 ng/mL a sensitivity of 97% and a negative predictive value 98% were found. CONCLUSIONS The use of an ultra-sensitive procalcitonin assay identifies patients with cirrhosis at very low risk of bacterial infections.
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Affiliation(s)
| | - Leila Haddad
- Liver Unit, Hospital Italiano, Buenos Aires, Argentina
| | - Alfredo Pedro Martínez
- Clinical Analysis Department, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno (CEMIC), Buenos Aires, Argentina
| | - María L Posadas
- Internal Medicine Research Unit, Hospital Italiano, Buenos Aires, Argentina
| | | | | | - Laura N Guerrero
- Clinical Analysis Department, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno (CEMIC), Buenos Aires, Argentina
| | - Ezequiel Ridruejo
- Liver Unit, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno (CEMIC), Buenos Aires, Argentina
| | - Oscar G Mandó
- Liver Unit, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno (CEMIC), Buenos Aires, Argentina
| | - Diego H Giunta
- Internal Medicine Research Unit, Hospital Italiano, Buenos Aires, Argentina
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Yang SK, Xiao L, Zhang H, Xu XX, Song PA, Liu FY, Sun L. Significance of serum procalcitonin as biomarker for detection of bacterial peritonitis: a systematic review and meta-analysis. BMC Infect Dis 2014; 14:452. [PMID: 25145785 PMCID: PMC4155125 DOI: 10.1186/1471-2334-14-452] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2013] [Accepted: 08/13/2014] [Indexed: 01/11/2023] Open
Abstract
Background Bacterial peritonitis is serious disease and remains a diagnostic challenge for clinicians. Many studies have highlighted the potential usefulness of procalcitonin (PCT) for identification of bacterial peritonitis, however, the overall diagnostic value of PCT remains unclear. Therefore, we performed a meta-analysis to assess the accuracy of PCT for detection of bacterial peritonitis. Methods We performed a systematic searched in MEDLINE, EMBASE, SCOPUS, China Biology Medicine Database (CBM), China National Knowledge Infrastructure Database (CNKI) and Cochrane databases for trials that evaluated the diagnostic role of PCT for bacterial peritonitis. Sensitivity, specificity and other measures of accuracy of PCT were pooled using bivariate random effects models. Results Eighteen studies involving 1827 patients were included in the present meta-analysis. The pooled sensitivity and specificity of serum PCT for the diagnosis bacterial peritonitis were 0.83 (95% CI: 0.76–0.89) and 0.92 (95% CI: 0.87–0.96), respectively. The positive likelihood ratio was 11.06 (95% CI: 6.31–19.38), negative likelihood ratio was 0.18 (95% CI: 0.12–0.27) and diagnostic odds ratio (DOR) was 61.52 (95% CI: 27.58–137.21). The area under the receiver operating characteristic curve (AUROC) was 0.94. Use of a common PCT cut-off value could improve the DOR to 75.32 and the AUROC to 0.95. Analysis of the seven studies that measured serum C-reactive protein (CRP) indicated that PCT was more accurate than CRP for the diagnosis of bacterial peritonitis. Conclusions Our results indicate that PCT determination is a relatively sensitive and specific test for the diagnosis of bacterial peritonitis. However, with regard to methodological limitations and significant heterogeneity, medical decisions should be based on both clinical findings and PCT test results. Electronic supplementary material The online version of this article (doi:10.1186/1471-2334-14-452) contains supplementary material, which is available to authorized users.
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Affiliation(s)
| | | | | | | | | | | | - Lin Sun
- Department of Nephrology, The Second Xiangya Hospital, Kidney Institute of Central South University, Changsha, Hunan 410011, China.
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Abstract
BACKGROUND Early diagnosis of sepsis in alcoholic hepatitis is important for selecting the appropriate therapy. The role of procalcitonin (PCT) to diagnose sepsis in patients with alcoholic hepatitis and systemic inflammatory response syndrome (SIRS) is not yet clear. METHODS All patients admitted with alcoholic hepatitis and SIRS underwent measurement of serum PCT and C reactive protein (CRP) levels within 24 h of admission. Patients were classified into two groups: group 1, alcoholic hepatitis with SIRS alone; group 2, alcoholic hepatitis with SIRS and sepsis. The ability of PCT to predict sepsis was evaluated using receiver-operating characteristic (ROC) analyses to compare the two groups. RESULTS The study included 11 patients in group 1 and 29 in group 2. All were male (median age 42 years; range, 24-65 years). Age, dose and duration of alcohol intake, biochemical parameters and median MELD score were not significantly different between the two groups. PCT and CRP were significantly higher among group 2 than group 1 patients (p < 0.05). ROC analysis showed an AUC of 0.81 (95 % CI 0.66-0.96) and 0.83 (95 % CI 0.68-0.93) for PCT and CRP, respectively, in distinguishing sepsis from SIRS without sepsis. A cutoff level of 0.57 mcg/l for PCT (sensitivity 79 %, specificity 82 %) for diagnosing sepsis in patients with alcoholic hepatitis and SIRS was comparable to a serum CRP cutoff level of 2.3 mg/dl (sensitivity 82.0 %, specificity 75 %). CONCLUSION Serum PCT can be a useful marker for diagnosing sepsis in patients with alcoholic hepatitis and SIRS and compares favorably with serum CRP levels.
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Affiliation(s)
- Kundan Kumar
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), MRA-A23, SGPGI Campus, Rae Bareli Road, Lucknow, 226014, Uttar Pradesh, India. .,Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raibareily Road, Lucknow, 226014, India.
| | - Samir Mohindra
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raibareily Road, Lucknow, 226014, India
| | - Mithun Raj
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raibareily Road, Lucknow, 226014, India
| | - Gourdas Choudhuri
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raibareily Road, Lucknow, 226014, India
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Lin KH, Wang FL, Wu MS, Jiang BY, Kao WL, Chao HY, Wu JY, Lee CC. Serum procalcitonin and C-reactive protein levels as markers of bacterial infection in patients with liver cirrhosis: a systematic review and meta-analysis. Diagn Microbiol Infect Dis 2014; 80:72-8. [PMID: 24974271 DOI: 10.1016/j.diagmicrobio.2014.03.029] [Citation(s) in RCA: 79] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2013] [Revised: 03/01/2014] [Accepted: 03/05/2014] [Indexed: 12/12/2022]
Abstract
The diagnostic value of procalcitonin (PCT) for patients with liver cirrhosis is unclear. We searched the PubMed, EMBASE, and Cochrane databases for studies published through December 2013 that evaluated the diagnostic performance of PCT for patients with acute or chronic liver disease with suspected systemic infection. We summarized the test performance characteristics by using forest plots, hierarchical summary receiver operating characteristic curves, and bivariate random effects models. Our search identified 230 citations, of which 10 diagnostic studies that evaluated 1144 patients and 435 bacterial infection episodes (32.1%) were ultimately included for analysis. The bivariate pooled sensitivity estimates were 79% (95% confidence interval [CI]: 64%-89%) for PCT tests and 77% (95% CI: 69%-84%) for C-reactive protein (CRP) tests. Pooled specificity estimates were higher for both PCT and CRP tests (PCT, 89% [95% CI: 82%-94%]; CRP, 85% [95% CI: 76%-90%]). The positive likelihood ratio for PCT (LR+, 7.38, 95% CI: 4.70-11.58) was sufficiently high to qualify PCT as a rule-in diagnostic tool, and the negative likelihood ratio for CRP was sufficiently low to qualify CRP as an acceptable rule-out diagnostic tool (LR- 0.23, 95% CI: 0.13-0.41) in patients with no signs of infection. Available clinical evidence showed that PCT has comparable accuracy to CRP for the diagnosis of systemic infection in patients with liver cirrhosis. Compared with patients with normal liver function, both PCT and CRP tests have acceptable accuracy for diagnosing bacterial infection among patients with liver cirrhosis.
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Affiliation(s)
- Kuan-Ho Lin
- College of Medicine, China Medical University, Taichung, 40402, Taiwan; Department of Emergency Medicine, China Medical University Hospital, Taichung, 40402, Taiwan
| | - Feng-Lin Wang
- Department of Emergency Medicine, Chang Gung Memorial Hospital, Taoyuan,Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Meng-Shu Wu
- Department of Emergency Medicine, Chang Gung Memorial Hospital, Taoyuan,Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Bing-Yan Jiang
- Department of Emergency Medicine, Chang Gung Memorial Hospital, Taoyuan,Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Wei-Liang Kao
- Department of Emergency Medicine, Chang Gung Memorial Hospital, Taoyuan,Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Hsiao-Yun Chao
- Department of Emergency Medicine, Chang Gung Memorial Hospital, Taoyuan,Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Jiunn-Yih Wu
- Department of Emergency Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan and Chang Gung University College of Medicine, Taoyuan, Taiwan.
| | - Chien-Chang Lee
- Department of Emergency Medicine, National Taiwan University Hospital Yunlin Brach, Yunlin, Taiwan; Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan.
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Procalcitonin and macrophage inflammatory protein-1 beta (MIP-1β) in serum and peritoneal fluid of patients with decompensated cirrhosis and spontaneous bacterial peritonitis. Adv Med Sci 2014; 59:52-6. [PMID: 24797975 DOI: 10.1016/j.advms.2013.07.006] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2013] [Accepted: 07/25/2013] [Indexed: 12/12/2022]
Abstract
PURPOSE Spontaneous bacterial peritonitis (SBP) is the most frequent infection in patients with cirrhosis causing significant mortality which requires rapid recognition for effective antibiotic therapy, whereas ascitic fluid cultures are frequently negative. The aim of this study was to evaluate the SBP diagnostic efficacy of procalcitonin (PCT) and macrophage inflammatory protein-1 beta (MIP-1β) measured in serum and peritoneal fluid. MATERIAL/METHODS Thirty-two participants with liver cirrhosis and ascites were included into the study (11 females and 21 males, mean age 49.5 ± 11.9 years). The peritoneal fluid and venous blood were collected for routine laboratory examinations and measurements of PCT and MIP-1β. Patients were divided into two groups according to the ascitic absolute polymorphonuclear leukocytes count (≥250 mm(-3) and <250 mm(-3)). RESULTS Ascites was sterile in 22 participants and SBP was diagnosed in 10 patients. Serum and ascitic levels of PCT and MIP-1β did not correlate with clinical and routine laboratory parameters. MIP-1β in the ascitic fluid was significantly higher in patients with SBP (213 ± 279 pg/ml vs. 66.3 ± 49.8 pg/ml; p=0.01). The sensitivity and specificity for diagnosis of SBP with ascitic MIP-1β were 80% and 72.7%, respectively (cut-off value 69.4 pg/ml) with AUROC 0.77 (95%CI 0.58-0.96). Serum levels of MIP-1β showed lower diagnostic yield. Serum and ascitic PCT levels were not different in patients with and without SBP. CONCLUSIONS MIP-1β concentration in ascitic fluid may distinguish patients with and without SBP with satisfactory sensitivity and specificity. Chemokines should be further explored for diagnostic use.
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Yuan LY, Ke ZQ, Wang M, Li Y. Procalcitonin and C-reactive protein in the diagnosis and prediction of spontaneous bacterial peritonitis associated with chronic severe hepatitis B. Ann Lab Med 2013; 33:449-54. [PMID: 24205495 PMCID: PMC3819445 DOI: 10.3343/alm.2013.33.6.449] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2012] [Revised: 03/24/2013] [Accepted: 07/15/2013] [Indexed: 12/11/2022] Open
Abstract
Background Procalcitonin (PCT), C-reactive protein (CRP), and white blood cells (WBCs) are inflammatory markers used to diagnose severe bacterial infections. We evaluated the diagnostic role of these markers and compared their accuracy for spontaneous bacterial peritonitis (SBP) associated with chronic severe hepatitis B (CSHB). Methods PCT and CRP concentrations, WBC count, and other hematological parameters were measured in serum from 84 well-characterized patients with CSHB, of whom 42 had SBP. Receiver operating characteristics (ROC) curve analysis was performed to assess the diagnostic accuracy. Results PCT and CRP concentrations were significantly higher in the CSHB patients with SBP (n=42) than CSHB patients without SBP (n=42). PCT and CRP concentrations were more accurate than WBC count for the diagnosis of CSHB-associated SBP. The optimal cutoff value of PCT was 0.48 ng/mL. The PCT concentration was significantly correlated with the CRP concentration and WBC count. Conclusions Serum PCT and CRP seems to be better markers than WBC for the diagnosis of CSHB patients with SBP.
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Affiliation(s)
- Le-Yong Yuan
- Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, P.R. China
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Lazzarotto C, Ronsoni MF, Fayad L, Nogueira CL, Bazzo ML, Narciso-Schiavon JL, de Lucca Schiavon L, Dantas-Corrêa EB. Acute phase proteins for the diagnosis of bacterial infection and prediction of mortality in acute complications of cirrhosis. Ann Hepatol 2013; 12:599-607. [PMID: 23813138 DOI: 10.1016/s1665-2681(19)31344-4] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Bacterial infection is a frequent complication in patients with decompensated liver cirrhosis and is related to high mortality rates during follow-up of these individuals. We sought to evaluate the diagnostic value of C-reactive protein (CRP) and procalcitonin (PCT) in diagnosing infection and to investigate the relationship between these biomarkers and mortality after hospital admission. MATERIAL AND METHODS Prospective study that included cirrhotic patients admitted to the hospital due to complications of the disease. The diagnostic accuracy of CRP and PCT for the diagnosis of infection was evaluated by estimating the sensitivity and specificity and by measuring the area under the receiver operating characteristics curve (AUROC). RESULTS A total of 64 patients and 81 hospitalizations were analyzed during the study. The mean age was 54.31 ± 11.87 years with male predominance (68.8%). Significantly higher median CRP and PCT levels were observed among infected patients (P < 0.001). The AUROC of CRP and PCT for the diagnosis of infection were 0.835 ± 0.052 and 0.860 ± 0.047, respectively (P = 0.273). CRP levels > 29.5 exhibited sensitivity of 82% and specificity of 81% for the diagnosis of bacterial infection. Similarly, PCT levels > 1.10 showed sensitivity of 67% and specificity of 90%. Significantly higher levels of CRP (P = 0.026) and PCT (P = 0.001) were observed among those who died within three months after admission. CONCLUSION CRP and PCT were reliable markers of bacterial infection in subjects admitted due to complications of liver cirrhosis and higher levels of these tests are related to short-term mortality in those patients.
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Affiliation(s)
- César Lazzarotto
- Division of Gastroenterology, Federal University of Santa Catarina, Brasil.
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Low eosinophil count predicts in-hospital mortality in cirrhosis with systemic inflammatory response syndrome. Eur J Gastroenterol Hepatol 2013; 25:676-82. [PMID: 23411865 DOI: 10.1097/meg.0b013e32835eb8f7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Absolute eosinophil count (AEC) and procalcitonin (PCT) level may have a prognostic value in critically ill patients. However, their role in cirrhotic patients has never been studied. We evaluated the role of AEC and PCT, obtained at admission, in predicting in-hospital mortality in cirrhotic patients with systemic inflammatory response syndrome (SIRS). PATIENTS AND METHODS In consecutive cirrhotic patients with SIRS (with or without sepsis), the levels of AEC and PCT were estimated at admission. Their outcome was correlated with these baseline parameters. RESULTS One hundred patients were enrolled [median age 52 (range 17-78) years, 84% men]. The etiology of cirrhosis was alcohol (47%), cryptogenic (35%), viral (13%), and others (5%). Their median model for end-stage liver disease (MELD) and Child-Turcotte-Pugh scores were 24 (range 6-40) and 11 (range 5-15), respectively. Infection was present in 59 patients and the rest of the 41 patients had SIRS without infection. There was a significant difference between the median levels of AEC and PCT between patients who had infection and those who did not have infection (P<0.01). Sixty-three patients recovered from SIRS and were discharged, 33 patients died, and four patients received orthotopic liver transplantation during the same admission. Baseline AEC and PCT levels were significantly different between patients who recovered and died. On multivariate analysis, baseline AEC values could independently predict in-hospital mortality, in addition to MELD and serum sodium. The area under receiver operating characteristic curve of AEC for predicting mortality was 0.785, and the best cutoff of AEC, obtained by Youden's index, was 104 cells/cumm, indicating that patients with baseline AEC values less than 104 cells/cumm had higher in-hospital mortality (sensitivity 78%, specificity 70%, positive predictive value 60%, negative predictive value 85%, and accuracy 73%). CONCLUSION In critically ill cirrhotic patients with SIRS, a baseline AEC value of less than 104 cells/cumm accurately predicts in-hospital mortality. The prediction of mortality by AEC is independent of the MELD score and serum sodium.
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Lahdou I, Sadeghi M, Oweira H, Fusch G, Daniel V, Mehrabi A, Jung GE, Elhadedy H, Schmidt J, Sandra-Petrescu F, Iancu M, Opelz G, Terness P, Schefold JC. Increased serum levels of quinolinic acid indicate enhanced severity of hepatic dysfunction in patients with liver cirrhosis. Hum Immunol 2013; 74:60-6. [DOI: 10.1016/j.humimm.2012.09.009] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2012] [Revised: 08/28/2012] [Accepted: 09/10/2012] [Indexed: 01/29/2023]
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Abstract
Bacterial infections are very frequent in advanced cirrhosis and become the first cause of death of these patients. Despite numerous experimental data and significant advances in the understanding of the pathogenesis of sepsis in cirrhosis, the outcome remains poor. Classical diagnostic parameters such as C-reactive protein and SIRS criteria have less diagnostic capacity in the cirrhotic population, often delaying the diagnosis and the management of bacterial infection. Prompt and appropriate empirical antibiotic treatment of infection and early resuscitation of patients with severe sepsis or septic shock are essential in determining patient's outcome. A strategy of careful restriction of prophylactic antibiotics to the high-risk populations could reduce the spread of multidrug resistant bacteria. This review is focused on the currently recommended diagnostic, therapeutic and prophylactic strategies for bacterial infections in the cirrhotic population.
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Affiliation(s)
- Javier Fernández
- Liver Unit, IMDiM, Hospital Clínic, Universidad de Barcelona, IDIBAPS and CIBERehd, Barcelona, Spain.
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Papp M, Vitalis Z, Altorjay I, Tornai I, Udvardy M, Harsfalvi J, Vida A, Kappelmayer J, Lakatos PL, Antal-Szalmas P. Acute phase proteins in the diagnosis and prediction of cirrhosis associated bacterial infections. Liver Int 2012; 32:603-611. [PMID: 22145664 DOI: 10.1111/j.1478-3231.2011.02689.x] [Citation(s) in RCA: 67] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2011] [Accepted: 10/26/2011] [Indexed: 12/21/2022]
Abstract
BACKGROUND Bacterial infections are common cause of morbidity and mortality in patients with cirrhosis. The early diagnosis of these infections is rather difficult. AIMS To assess the accuracy of acute phase proteins in the identification of bacterial infections. METHODS Concentration of C-reactive protein (CRP), procalcitonin (PCT), lipopolysaccharide-binding protein (LBP), sCD14 and antimicrobial antibodies were measured in serum of 368 well-characterized patients with cirrhosis of whom 139 had documented infection. Clinical data was gathered by reviewing the patients' medical charts. RESULTS Serum levels of CRP, PCT and LBP were significantly higher in patients with clinically overt infections. Among the markers, CRP - using a 10 mg/L cut-off value- proved to be the most accurate in identifying patients with infection (AUC: 0.93). The accuracy of CRP, however, decreased in advanced stage of the disease, most probably because of the significantly elevated CRP levels in non-infected patients. Combination of CRP and PCT increased the sensitivity and negative predictive value, compared with CRP on its own, by 10 and 5% respectively. During a 3-month follow-up period in patients without overt infections, Kaplan-Meier and proportional Cox-regression analyses showed that a CRP value of >10 mg/L (P = 0.035) was independently associated with a shorter duration to progress to clinically significant bacterial infections. There was no correlation between acute phase protein levels and antimicrobial seroreactivity. CONCLUSIONS C-reactive protein on its own is a sensitive screening test for the presence of bacterial infections in cirrhosis and is also a useful marker to predict the likelihood of clinically significant bacterial infections in patients without overt infections.
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Affiliation(s)
- Maria Papp
- 2nd Department of Medicine, Division of Gastroenterology, University of Debrecen, Debrecen, Hungary.
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Li CH, Yang RB, Pang JHS, Chang SS, Lin CC, Chen CH, Chen HY, Chiu TF. Procalcitonin as a biomarker for bacterial infections in patients with liver cirrhosis in the emergency department. Acad Emerg Med 2011; 18:121-6. [PMID: 21276124 DOI: 10.1111/j.1553-2712.2010.00991.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES The objective was to determine the diagnostic accuracy of procalcitonin measurement for bacterial infections in patients with all causes of liver cirrhosis. METHODS The authors conducted a cross-sectional study of 98 patients with cirrhosis treated in the emergency department (ED) of Chang-Gung Memorial Hospital, Taiwan. Serum procalcitonin levels and other clinical information were obtained concurrently. Patients were assigned to a sepsis or nonsepsis group after the medical records were reviewed by two emergency physicians blinded to the study. Receiver operating characteristic (ROC) curve analysis was conducted to determine the sensitivity, specificity, likelihood ratio, and suggested cutoff values. The diagnostic accuracy of the C-reactive protein (CRP) level was also determined for comparison. RESULTS A total of 98 patients were enrolled for analysis in 1 year. Twenty-seven patients (27.6%) were assigned to the sepsis group. Eleven patients (11.2%) had positive blood cultures. The areas under the ROC curves for procalcitonin and CRP in predicting sepsis were 0.89 (95% confidence interval [CI] = 0.77 to 0.92) and 0.81 (95% CI = 0.72 to 0.89), respectively (p = 0.11). The cutoff that maximized Youden's index was 0.49 ng/mL for procalcitonin and 24.7 mg/L for CRP. At these cutoffs, the sensitivity and specificity were 81.5 and 87.3% for procalcitonin and 80.0 and 80.3% for CRP. These results suggest that procalcitonin measurement shows at least an equivalent diagnostic accuracy to CRP measurement. CONCLUSIONS Procalcitonin provided satisfactory diagnostic accuracy in differentiating bacterial infections in patients with all causes of liver cirrhosis in the ED. A cutoff value of 0.5 ng/mL is suggested for clinical use.
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Affiliation(s)
- Chih-Huang Li
- Department of Emergency Medicine, Chang-Gung Memorial Hospital, Keelung Branch, Taipei, Taiwan, ROC
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Oruc N, Ozutemiz O, Yuce G, Akarca US, Ersoz G, Gunsar F, Batur Y. Serum procalcitonin and CRP levels in non-alcoholic fatty liver disease: a case control study. BMC Gastroenterol 2009; 9:16. [PMID: 19222849 PMCID: PMC2656521 DOI: 10.1186/1471-230x-9-16] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2008] [Accepted: 02/17/2009] [Indexed: 12/16/2022] Open
Abstract
Background Both C reactive protein (CRP) and procalcitonin (PCT) are well known acute phase reactant proteins. CRP was reported to increase in metabolic syndrome and type-2 diabetes. Similarly altered level of serum PCT was found in chronic liver diseases and cirrhosis. The liver is considered the main source of CRP and a source of PCT, however, the serum PCT and CRP levels in non-alcoholic fatty liver disease (NAFLD) were not compared previously. Therefore we aimed to study the diagnostic and discriminative role of serum PCT and CRP in NAFLD. Methods Fifty NAFLD cases and 50 healthy controls were included to the study. Liver function tests were measured, body mass index was calculated, and insulin resistance was determined by using a homeostasis model assessment (HOMA-IR). Ultrasound evaluation was performed for each subject. Serum CRP was measured with nephalometric method. Serum PCT was measured with Kryptor based system. Results Serum PCT levels were similar in steatohepatitis (n 20) and simple steatosis (n 27) patients, and were not different than the control group (0.06 ± 0.01, 0.04 ± 0.01 versus 0.06 ± 0.01 ng/ml respectively). Serum CRP levels were significantly higher in simple steatosis, and steatohepatitis groups compared to healthy controls (7.5 ± 1.6 and 5.2 ± 2.5 versus 2.9 ± 0.5 mg/dl respectively p < 0.01). CRP could not differentiate steatohepatitis from simple steatosis. Beside, three patients with focal fatty liver disease had normal serum CRP levels. Conclusion Serum PCT was within normal ranges in patients with simple steatosis or steatohepatitis and has no diagnostic value. Serum CRP level was increased in NAFLD compared to controls. CRP can be used as an additional marker for diagnosis of NAFLD but it has no value in discrimination of steatohepatitis from simple steatosis.
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Affiliation(s)
- Nevin Oruc
- Gastroenterology Department, Ege University Faculty of Medicine, Izmir, Turkey.
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Eyraud D, Ben Ayed S, Tanguy ML, Vézinet C, Siksik JM, Bernard M, Fratéa S, Movschin M, Vaillant JC, Coriat P, Hannoun L. Procalcitonin in liver transplantation: are high levels due to donors or recipients? CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2008; 12:R85. [PMID: 18601732 PMCID: PMC2575559 DOI: 10.1186/cc6942] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/11/2008] [Revised: 06/24/2008] [Accepted: 07/04/2008] [Indexed: 11/10/2022]
Abstract
Introduction To date, a specific marker to evaluate and predict the clinical course or complication of the liver-transplanted patient is not available in clinical practice. Increased procalcitonin (PCT) levels have been found in infectious inflammation; poor organ perfusion and high PCT levels in the cardiac donor appeared to predict early graft failure. We evaluated PCT as a predictor of early graft dysfunction and postoperative complications. Methods PCT serum concentrations were measured in samples collected before organ retrieval from 67 consecutive brain-dead donors and in corresponding recipients from day 0, before liver transplantation, up to day 7 after liver transplantation. The following parameters were recorded in donors: amount of vasopressive drug doses, cardiac arrest history 24 hours before retrieval, number of days in the intensive care unit, age of donor, and infection in donor, and the following parameters were recorded in recipients: cold and warm ischemia time, veno-venous bypass, transfusion amount during orthotopic liver transplantation (OLT), and occurrence of postoperative complication or hepatic dysfunction. Results In the donor, the preoperative level of PCT was associated with cardiac arrest and high doses of catecholamines before organ retrieval. In the recipient, elevated PCT levels were observed early after OLT, with a peak at day 1 or 2 after OLT, then a decrease until day 7. A postoperative peak of PCT levels was associated neither with preoperative PCT levels in the donor or the recipients nor with hepatic post-OLT dysfunction or other postoperative complications, but with two donor parameters: infection and cardiac arrest. Conclusion PCT level in the donor and early PCT peak in the recipient are not predictive of post-OLT hepatic dysfunction or other complications. Cardiac arrest and infection in the donor, but not PCT level in the donor, are associated with high post-OLT PCT levels in the recipient.
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Affiliation(s)
- Daniel Eyraud
- Département d'Anesthésie-Réanimation, Hôpital Pitié-Salpêtrière 43-47 Boulevard de l'Hôpital, 75013 Paris, France.
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Elsing C, Harenberg S, Stremmel W, Herrmann T. Serum levels of soluble Fas, nitric oxide and cytokines in acute decompensated cirrhotic patients. World J Gastroenterol 2007; 13:421-5. [PMID: 17230612 PMCID: PMC4065898 DOI: 10.3748/wjg.v13.i3.421] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate plasma levels of nitrite/nitrate (NOx), soluble Fas (sFas) antigen, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in patients with compensated and acute decompensated cirrhosis and to evaluate mediators causing acute decompensation in liver cirrhosis.
METHODS: This prospective study was conducted in the medical intensive care unit of an academic tertiary center. Fifty-five patients with acute decompensation (gastrointestinal hemorrhage, encephalopathy, hydropic decompensation) and twenty-five patients with compensated liver cirrhosis were included. Blood samples were taken for analyses of sFas, Nox, IL-6, TNF-α. Liver enzymes and kidney functions were also tested.
RESULTS: In patients with acute decompensation, plasma sFas levels were higher than in non-decompensated patients (15 305 ± 4646 vs 12 458 ± 4322 pg/mL, P < 0.05). This was also true for the subgroup of patients with alcoholic liver cirrhosis (P < 0.05). The other mediators were not different and none of the parameters predicted survival, except for ALT (alanine-aminotransferase). In patients with portal-hypertension-induced acute hemorrhage, NOx levels were significantly lower than in patients with other forms of decompensation (70.8 ± 48.3 vs 112.9 ± 74.9 pg/mL, P < 0.05). When NOx levels were normalized to creatinine levels, the difference disappeared. IL-6, TNF-α and sFas were not different between bleeders and non-bleeders. In decompensated patients sFas, IL-6 and NOx levels correlated positively with creatinine levels, while IL-6 levels were dependent on Child class.
CONCLUSION: In acute decompensated cirrhotic patients sFas is increased, suggesting a role of apoptosis in this process and patients with acute bleeding have lower NOx levels. However, in this acute complex clinical situation, kidney function seems to have a predominant influence on mediator levels.
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Affiliation(s)
- Christoph Elsing
- Gastroenterology, Department of Medicine, St. Elisabeth-Hospital, PO Box 580, Dorsten 46225, Germany.
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Elefsiniotis IS, Skounakis M, Vezali E, Pantazis KD, Petrocheilou A, Pirounaki M, Papatsibas G, Kontou-Kastellanou C, Moulakakis A. Clinical significance of serum procalcitonin levels in patients with acute or chronic liver disease. Eur J Gastroenterol Hepatol 2006; 18:525-30. [PMID: 16607149 DOI: 10.1097/00042737-200605000-00012] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
OBJECTIVE To evaluate the diagnostic value of serum procalcitonin levels in patients with acute or chronic liver disease, with or without bacterial infections and to correlate the results with the clinical outcome and the laboratory findings for these patients. METHODS One hundred and six consecutive hospitalized patients with liver disease were evaluated for procalcitonin levels on admission. Fifteen of them (14.2%) had acute alcoholic hepatitis on cirrhotic background (group A), 20 (18.9%) had alcoholic cirrhosis without hepatitis and/or bacterial infection (group B), 16 (15.1%) had decompensated cirrhosis with proved bacterial infection (group C), 42 (39.6%) had uncomplicated viral hepatitis-related cirrhosis (group D) and 13 (12.3%) had acute icteric viral hepatitis (group E). Serum procalcitonin levels were measured using an immunoluminometric assay. Statistical analysis was based on Student's t-test and the non-parametric Kruskall-Wallis test (P<0.05). RESULTS Serum procalcitonin levels were significantly higher in cirrhotic patients with bacterial infection (9.80+/-16.80 ng/ml) than in those without bacterial infection (0.21+/-0.13 ng/ml, P=0.001), whereas they were within normal range (<0.5 ng/ml) in all patients with uncomplicated cirrhosis, irrespective of the cause of cirrhosis. Seven of 15 group A patients (46.2%) and 4/13 group E patients (30.8%), all of them cirrhotics, had procalcitonin levels higher than 0.5 ng/ml on admission, without established bacterial infection. CONCLUSION Serum procalcitonin levels remain below the threshold of 0.5 ng/ml in all patients with uncomplicated cirrhosis, irrespective of the cause of the disease, while they are significantly elevated when bacterial infection complicates the course of the disease. A significant proportion of patients with acute alcoholic hepatitis on a cirrhotic background as well as of patients with acute on chronic viral hepatitis, without bacterial infection, exhibit serum procalcitonin levels above 0.5 ng/ml, suggesting that this cut-off value is probably not enough to discriminate between patients with or without bacterial infection within these subgroups of patients with liver disease.
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Affiliation(s)
- Ioannis S Elefsiniotis
- Department of Internal Medicine, Hippokration Hospital of Athens, Carchidonos 9, A. Glyfada, GR-16562 Greece.
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