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Li S, Niu XX, Liu JL, Su M, Li QQ, Wang CY, Wang JJ, Chen HY, Ji D. Leveraging the gut microbiome to understand the risk factor of cognitive impairment in patients with liver cirrhosis. Eur J Gastroenterol Hepatol 2025; 37:627-637. [PMID: 39976005 DOI: 10.1097/meg.0000000000002934] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/21/2025]
Abstract
OBJECTIVES The role of the gut-liver axis in liver cirrhosis is becoming increasingly recognized. We investigated the fecal microbiome in patients with liver cirrhosis and its potential function as a predictive biomarker of hepatic encephalopathy. METHODS Patients were divided into either a high plasma ammonia (HPA) group or a low plasma ammonia (LPA) group according to the upper limit of normal of plasma ammonia concentration. 16S rRNA sequencing of fecal samples was performed to study how the microbiota affects the clinical symptoms of liver cirrhosis. The Stroop test was used to assess the ability of the brain to inhibit habitual behaviors. RESULTS Totally, 21 subjects were enrolled. Among the 18 patients with liver cirrhosis, 14 were male, the age range was 42-56 years, and the plasma ammonia level range was 20-125.9 μmol/l. The Stroop test showed more severe cognitive impairment in HPA than in LPA individuals. At the same time, there were significant differences in fecal microbiome characteristics between the two groups, characterized by a further increase in the abundance of the Proteobacteria phylum in the gut (especially aerobic Enterobacteriaceae ). Function predictions of Phylogenetic Investigation of Communities by Reconstruction of Unobserved States in the microbiome further explained the increase in the Enterobacteriaceae -dominated polyamine synthesis pathway in the gut microbiome of HPA groups. CONCLUSION Cirrhotic patients with hyperammonemia have a specific fecal bacterial composition (characterized via expansion of Enterobacteriaceae ). The ability to bio-synthesize polyamines that Enterobacteriaceae possesses is likely to be a key factor in the elevation of plasma ammonia.
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Affiliation(s)
- Shuyao Li
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital
| | - Xiao-Xia Niu
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital
| | - Jia-Liang Liu
- Department of General Internal Medicine, Hospital of North China Electric Power University, Beijing, China
| | - Min Su
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital
| | - Qian-Qian Li
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital
| | - Chun-Yan Wang
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital
| | - Jian-Jun Wang
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital
| | - Hong-Yan Chen
- Department of General Internal Medicine, Hospital of North China Electric Power University, Beijing, China
| | - Dong Ji
- Senior Department of Hepatology, the Fifth Medical Center of PLA General Hospital
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McPherson S, Abbas N, Allison MED, Backhouse D, Boothman H, Cooksley T, Corless L, Crame T, Cross TJS, Henry J, Hogan B, Mansour D, McGinty G, McKinnon G, Patel J, Tavabie OD, Williams F, Hollywood C. Decompensated cirrhosis: an update of the BSG/BASL admission care bundle. Frontline Gastroenterol 2025:flgastro-2025-103074. [DOI: 10.1136/flgastro-2025-103074] [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: 05/03/2025] Open
Abstract
Acute decompensated cirrhosis (DC) and acute-on-chronic liver failure are common reasons for hospital admission that have a high in-hospital mortality rate (10%–20%). Patients require a detailed assessment for precipitating factors and management of complications such as infections, ascites, acute kidney injury and hepatic encephalopathy. Multiple reports have demonstrated unwarranted variability in the care of patients with DC. In 2014, the British Society of Gastroenterology (BSG)/British Association for the Study of the Liver (BASL) DC care bundle (DCCB) was introduced to provide a structured approach for the management of patients with DC in the first 24 hours. Usage of the DCCB has been shown to improve care of patients with DC. However, despite evidence indicating the beneficial impact of the DCCB, overall usage across the UK was only 11.4% in a national audit. Our aim was to update the DCCB to incorporate recent advances in care and improve its usability and develop a strategy to improve its usage nationally. The updated bundle was developed by a multidisciplinary group of specialists from BSG, BASL and the Society for Acute Medicine with the quality of evidence supporting the bundle recommendations assessed using the Grading of Recommendation Assessment Development and Evaluation tool. Proposed minimum standards for audit were also developed. Finally, a strategy to promote usage of the bundle including education/training at a national and local level, improving accessibility for the bundle, and promotion of frameworks for use at an institutional level to improve and monitor utilisation of DCCB.
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Yi K, Ma Y, Zhang P, He H, Lin Y, Sun D. Environmental and Clinical Factors Concerning Gastrointestinal Bleeding: An Umbrella Review of Meta-Analyses. J Am Med Dir Assoc 2025; 26:105412. [PMID: 39818418 DOI: 10.1016/j.jamda.2024.105412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 11/05/2024] [Accepted: 11/05/2024] [Indexed: 01/18/2025]
Abstract
OBJECTIVES Gastrointestinal bleeding, an emergency and critical disease, is affected by multiple factors. This study aims to systematically summarize and appraise various factors associated with gastrointestinal bleeding. DESIGN Umbrella review. SETTING AND PARTICIPANTS Meta-analyses that evaluated environmental and clinical factors concerning gastrointestinal bleeding. METHODS We conducted a systematic search to identify eligible meta-analyses. For each included study, the risk estimates, heterogeneity estimates, small-study effects, excess significance tests, and publication biases were recalculated and appraised. Furthermore, we considered the methodologic quality and classified the evidence. RESULTS In this study, 51 beneficial and 44 harmful associations were found. This study found that preemptive transjugular intrahepatic portosystemic shunt was the most reliable treatment to reduce gastroesophageal variceal bleeding and mortality risk, followed by antibiotics. For gastroduodenal ulcer bleeding, Yunnan Baiyao and proton pump inhibitors (PPIs) were relatively dependable treatment drugs, and the comparatively reliable prophylactic drugs comprised PPIs and H2-receptor antagonists. Patients with hemodynamic instability and larger ulcers had a higher risk of rebleeding. Both weekend admissions and the combination of selective serotonin reuptake inhibitors and nonsteroidal anti-inflammatory drugs were high-risk factors for upper gastrointestinal bleeding and mortality. We also found that tranexamic acid was a credible drug for overall gastrointestinal bleeding. Meanwhile, aspirin, warfarin, diabetes, and renal failure were all high-risk factors. CONCLUSIONS AND IMPLICATIONS Altogether, many factors can substantially influence gastrointestinal bleeding. Therefore, in daily life and clinical practice, we should not only remain cautious in prescribing and taking some drugs but also pay attention to the management of lifestyle and underlying diseases. If necessary, protective drugs should be properly supplemented.
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Affiliation(s)
- Keqian Yi
- Department of Gastrointestinal Surgery, Second Affiliated Hospital of Kunming Medical University/Second Faculty of Clinical Medicine, Kunming Medical University, Kunming, China
| | - Yu Ma
- Department of Gastroenterology, Second Affiliated Hospital of Kunming Medical University/Second Faculty of Clinical Medicine, Kunming Medical University, Kunming, China
| | - Pengcheng Zhang
- Department of Gastrointestinal Surgery, Second Affiliated Hospital of Kunming Medical University/Second Faculty of Clinical Medicine, Kunming Medical University, Kunming, China
| | - Haiyu He
- Department of Gastroenterology, Second Affiliated Hospital of Kunming Medical University/Second Faculty of Clinical Medicine, Kunming Medical University, Kunming, China.
| | - Yueying Lin
- Department of Gastrointestinal Surgery, Second Affiliated Hospital of Kunming Medical University/Second Faculty of Clinical Medicine, Kunming Medical University, Kunming, China.
| | - Dali Sun
- Department of Gastrointestinal Surgery, Second Affiliated Hospital of Kunming Medical University/Second Faculty of Clinical Medicine, Kunming Medical University, Kunming, China
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Wang T, Wang D, Shi R, Zeng X, Yang P, Chen X, Chen S, Qin C, Wan C, Wang J. Relationship between coagulopathy score and survival in critically ill patients with liver cirrhosis and sepsis: a retrospective study. BMC Infect Dis 2025; 25:418. [PMID: 40140996 PMCID: PMC11948833 DOI: 10.1186/s12879-025-10848-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Accepted: 03/21/2025] [Indexed: 03/28/2025] Open
Abstract
BACKGROUND This research focused on exploring the association between coagulopathy scores and the survival outcomes, both short-term and long-term, in individuals diagnosed with liver cirrhosis complicated by sepsis. METHODS This study retrospectively analyzed data from individuals with liver cirrhosis and sepsis who were admitted to the intensive care unit (ICU) at Beth Israel Deaconess Medical Center between 2008 and 2022. The main outcome of interest was all-cause mortality within 28 days post-admission, while the secondary outcome assessed mortality within 90 days. We used the Kaplan-Meier analysis to compare the mortality risk among the different groups. To evaluate the relationship between coagulopathy score and mortality risk in patients with liver cirrhosis and sepsis, a multivariate Cox proportional hazards regression analysis was performed. The predictive performance of the coagulopathy score for short- and long-term all-cause mortality was assessed using receiver operating characteristic (ROC) curve analysis, which included evaluation of its sensitivity, specificity, and area under the curve. Subgroup analyses were performed to evaluate the relationship between coagulopathy score and survival across different groups. RESULTS The study included a total of 2,278 patients. Kaplan-Meier survival analysis demonstrated that individuals with elevated coagulopathy scores exhibited markedly higher rates of ICU mortality, in-hospital mortality, as well as 28-day and 90-day mortality, with all log-rank tests yielding P-values of less than 0.001. The results of the multivariate Cox regression analysis showed that an elevated coagulopathy score was independently linked to higher 28-day and 90-day all-cause mortality, both before and after controlling for potential confounders. ROC curve analysis showed that although the coagulopathy score was slightly less predictive of prognosis than the Model for End-stage Liver Disease score, it significantly outperformed the Sequential Organ Failure Assessment score and the Sepsis-induced Coagulopathy score. Subgroup analysis revealed no significant interaction between the coagulopathy score and survival across the different subgroups. CONCLUSIONS Higher coagulopathy scores in critically ill patients with liver cirrhosis and sepsis were independently associated with poor prognosis. Due to its simplicity and potential predictive value, the coagulopathy score can serve as an effective complement to existing clinical tools for managing critically ill patients with liver cirrhosis and sepsis.
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Affiliation(s)
- Tao Wang
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Decai Wang
- Department of Urology, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, 621000, China
| | - Ruizi Shi
- Department of Hepatobiliary Surgery, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, 621000, China
| | - Xintao Zeng
- Department of Hepatobiliary Surgery, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, 621000, China
| | - Pei Yang
- Department of Hepatobiliary Surgery, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, 621000, China
| | - Xi Chen
- Department of Hepatobiliary Surgery, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, 621000, China
| | - Sirui Chen
- Department of Hepatobiliary Surgery, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, 621000, China
| | - Chuan Qin
- Department of Hepatobiliary Surgery, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, 621000, China
| | - Chidan Wan
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Jianjun Wang
- Department of Hepatobiliary Surgery, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, 621000, China.
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Aziz AA, Aziz MA, Amir M, Shah R, Ali IA. Outcomes of Acute Pancreatitis in Patients With and Without Liver Cirrhosis: A Retrospective Analysis. Cureus 2025; 17:e78933. [PMID: 40092023 PMCID: PMC11909785 DOI: 10.7759/cureus.78933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/10/2025] [Indexed: 03/19/2025] Open
Abstract
Background Acute pancreatitis (AP) is a common cause of hospitalization in the United States. Our study aimed to investigate the impact of liver cirrhosis (LC) on the outcomes of AP in adult patients hospitalized with AP. Methods We performed a retrospective study of adult patients with AP utilizing the Nationwide Inpatient Sample (NIS) database from 2020 to 2022. We compared AP outcomes in patients with and without LC. The primary outcome was all-cause inpatient mortality. Secondary outcomes were the length of stay (LOS), healthcare cost utilization adjusted to 2022, the incidence of acute renal failure (ARF), sepsis, shock, venous thromboembolism (VTE), and the need for intensive care unit (ICU) admission. Statistical analyses were performed using STATA, version 16.1 (StataCorp., College Station, Texas, USA). A multivariate logistic regression analysis was conducted to assess if gender was an independent predictor for these outcomes and to adjust for any confounders. Results From 2020 to 2022, 738,139 adult patients underwent AP admissions. Among the patients, 723,959 had AP without LC, and 14,180 had AP with LC. The mean age for patients with and without LC was the same, 50.9 years. Patients without LC had a higher prevalence of cerebrovascular accident (CVA) and obesity. Patients with LC had a higher prevalence of congestive heart failure (CHF), diabetes mellitus type 2 (DM2), diabetes mellitus type 1 (DM1), chronic kidney disease (CKD), and smoking/tobacco use. We found that AP patients with LC had a significantly higher likelihood of in-hospital mortality (aOR: 1.74, 95% CI: 1.22-2.42, P < 0.01), longer LOS (+ 0.46 days, 95% CI: 0.26-0.67, P < 0.01), higher healthcare utilization cost (+ $4163, 95% CI: $1530.9-$6796.0, P < 0.01), shock (aOR: 1.87, 95% CI: 1.42-2.46, P < 0.01), ARF (aOR: 1.44, 95% CI: 1.30-1.59, P < 0.01), ICU admission (aOR: 1.67, 95% CI: 1.38-1.91, P < 0.01), and acute VTE (aOR: 1.65, 95% CI: 1.30-2.11, P < 0.01). Conclusions We found that patients with AP who concomitantly had LC had significantly poor clinical outcomes, including higher mortality, ARF, shock, ICU admission, VTE, LOS, and total hospitalization charges as compared to AP patients who did not have LC. Our study highlights that cirrhotic patients with AP have poor inpatient hospital outcomes and need aggressive treatment to prevent morbidity and mortality.
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Affiliation(s)
- Ahmed Ali Aziz
- Internal Medicine, INTEGRIS Health Baptist Medical Center, Oklahoma City, USA
| | - Muhammad Ali Aziz
- Internal Medicine, University of Kentucky College of Medicine, Lexington, USA
| | - Muhammad Amir
- Transplant Hepatology, INTEGRIS Health Baptist Medical Center, Oklahoma City, USA
| | - Rehan Shah
- Internal Medicine, Bayonne Medical Center, Bayonne, USA
| | - Ijlal Akbar Ali
- Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, USA
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Liu T, Wu G, Gudd CLC, Trovato FM, Barbera T, Liu Y, Triantafyllou E, McPhail MJW, Thursz MR, Khamri W. Cis-interaction between CD52 and T cell receptor complex interferes with CD4 + T cell activation in acute decompensation of cirrhosis. EBioMedicine 2024; 108:105336. [PMID: 39276679 PMCID: PMC11418137 DOI: 10.1016/j.ebiom.2024.105336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Revised: 08/27/2024] [Accepted: 08/29/2024] [Indexed: 09/17/2024] Open
Abstract
BACKGROUND Immune dysfunction contributes to a high rate of infection in patients with acute decompensation of cirrhosis. CD52 is a glycoprotein prominently expressed in lymphocytes. Immune regulation by CD52 may be involved in adaptive immune dysfunction in cirrhosis. This study aimed to investigate the function of CD52 on CD4+ T cells on the blood of patients with acute decompensation of cirrhosis. METHODS The expression of CD52 in the peripheral blood lymphocytes of 49 patients with cirrhosis was investigated using flow cytometry and transcriptomics. Potential cis-membrane ligands of CD52 were discovered via proximity labelling followed by proteomics. The function of CD52 on antigen-specific activation of CD4+ T cells was examined using flow cytometry in CD52 CRISPR-Cas9 knockout primary T cells. FINDINGS CD52 expression was elevated in CD4+ T cells in acute decompensation of cirrhosis, and this elevation was correlated with increased disease severity and mortality. Components of the T cell receptor complex including TCRβ, CD3γ and CD3ε were identified and validated as cis-membrane ligands of CD52. Knockout of CD52 promoted antigen-specific activation, proliferation, and pro-inflammatory cytokine secretion. INTERPRETATION Membrane bound CD52 demonstrated cis-interaction with the T cell receptor and served as a dynamic regulator of antigen-specific activation of CD4+ T cells. The upregulation of CD52 in the periphery of acute decompensation of cirrhosis hinders the recognition of the T cell receptor by MHC, contributing to impaired T cell function. The development of an alternative anti-CD52 antibody is required to restore T cell function and prevent infections in cirrhosis. FUNDING This study was supported by the NIHR Imperial Biomedical Research Centre, Institute for Translational Medicine and Therapeutics (P74713), Wellcome Trust (218304/Z/19/Z), and Medical Research Council (MR/X009904/1 and MR/R014019/1).
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Affiliation(s)
- Tong Liu
- Section of Hepatology & Gastroenterology, Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, United Kingdom
| | - Gang Wu
- Department of Life Sciences, Imperial College London, London, United Kingdom
| | - Cathrin L C Gudd
- Section of Hepatology & Gastroenterology, Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, United Kingdom
| | - Francesca M Trovato
- Department of Inflammation Biology, Institute of Liver Studies, King's College London, London, United Kingdom
| | - Thomas Barbera
- Section of Hepatology & Gastroenterology, Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, United Kingdom
| | - Yan Liu
- Glycosciences Laboratory, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, United Kingdom
| | - Evangelos Triantafyllou
- Section of Hepatology & Gastroenterology, Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, United Kingdom
| | - Mark J W McPhail
- Department of Inflammation Biology, Institute of Liver Studies, King's College London, London, United Kingdom
| | - Mark R Thursz
- Section of Hepatology & Gastroenterology, Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, United Kingdom
| | - Wafa Khamri
- Section of Hepatology & Gastroenterology, Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, United Kingdom.
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Pan Z, Lin J, Huo C, Yin D, Guo Q. Increased serum albumin corrected anion gap levels are associated with poor prognosis in septic patients with liver cirrhosis. Sci Rep 2024; 14:21510. [PMID: 39277682 PMCID: PMC11401841 DOI: 10.1038/s41598-024-72703-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 09/10/2024] [Indexed: 09/17/2024] Open
Abstract
The prognosis of septic patients with cirrhosis is worse compared to septic patients without cirrhosis. Early and accurate prognosis determination in patients with cirrhosis and sepsis is pivotal for guiding treatment decisions. The aim of this study was to investigate the association between albumin-corrected anion gap (ACAG) and clinical prognosis of patients with sepsis and cirrhosis. This study extracted data of patients with sepsis and cirrhosis from the Medical Information Mart for Intensive Care (MIMIC-IV) database. A total of 1340 patients (64.6% male) were enrolled. After confounders adjusting, elevated ACAG had a significant association with 28-day mortality (HR1.604; 95% CI 1.258-2.048; P < 0.001). Restricted cubic spline revealed that a linear relationship between ACAG and 28-day mortality (P-nonlinear = 0.089, P-overall = 0.001). According to the ROC curve analysis, the ACAG demonstrated a higher area under the curve (AUC) of 0.703 compared to AG (0.675). Kaplan-Meier analysis revealed higher 28-day mortality in high ACAG group (log-rank test, χ^2 = 175.638, P < 0.001). Furthermore, subgroup analysis showed a significant interaction between ACAG and etiology of cirrhosis (P for interaction = 0.014). Therefore, ACAG could provide clinicians with valuable insights for guiding interventions in this high-risk population.
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Affiliation(s)
- Zetao Pan
- Department of Critical Care Medicine, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital), Suzhou, Jiangsu, China
| | - Jiancheng Lin
- Department of Critical Care Medicine, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital), Suzhou, Jiangsu, China
| | - Cunyang Huo
- Department of Critical Care Medicine, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital), Suzhou, Jiangsu, China
| | - Di Yin
- Department of Critical Care Medicine, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital), Suzhou, Jiangsu, China
| | - Qiang Guo
- Department of Critical Care Medicine, The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital), Suzhou, Jiangsu, China.
- Department of Emergency and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
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Du L, Wei N, Maiwall R, Song Y. Differential diagnosis of ascites: etiologies, ascitic fluid analysis, diagnostic algorithm. Clin Chem Lab Med 2024; 62:1266-1276. [PMID: 38112289 DOI: 10.1515/cclm-2023-1112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Accepted: 12/07/2023] [Indexed: 12/21/2023]
Abstract
Ascites is the pathological accumulation of fluid within the peritoneal cavity. It often occurs as results of liver cirrhosis, malignant neoplasia, tuberculous infection, cardiac insufficiency, renal diseases, etc. Determining the etiology is an essential step in the management of patients with new-onset ascites. Abdominal paracentesis with appropriate ascitic fluid analysis is probably the most cost-effective method of determining the cause of ascites. We performed a literature search of PubMed and identified articles published in the field of ascites, to evaluate diagnostic values of various parameters in defining the etiologies of ascites and then provides diagnostic algorithm for patients with new-onset ascites. In patients with ascites, the constituent ratio of underlying etiology varies between developed and developing countries. It is a challenge to define the etiologies of ascites in developing countries. Routine ascitic fluid analysis should include the serum ascites albumin gradient (SAAG), total protein concentration, cell count and differential. Optional ascitic fluid analysis includes cholesterol, fluid culture, cytology, tumor markers, lactate dehydrogenase, adenosine deaminase (ADA), triglyceride, amylase, glucose, brain natriuretic peptide (BNP), etc. Our review evaluated diagnostic values of the above parameters in defining the etiologies of ascites. Diagnostic algorithm established in this review would provide a practical and convenient diagnostic strategy for clinicians in diagnosing patients with new-onset ascites.
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Affiliation(s)
- Li Du
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
| | - Ning Wei
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
| | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Yuhu Song
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
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L'Écuyer S, Charbonney E, Carrier FM, Rose CF. Implication of Hypotension in the Pathogenesis of Cognitive Impairment and Brain Injury in Chronic Liver Disease. Neurochem Res 2024; 49:1437-1449. [PMID: 36635437 DOI: 10.1007/s11064-022-03854-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 09/23/2022] [Accepted: 12/26/2022] [Indexed: 01/14/2023]
Abstract
The incidence of chronic liver disease is on the rise. One of the primary causes of hospital admissions for patients with cirrhosis is hepatic encephalopathy (HE), a debilitating neurological complication. HE is defined as a reversible syndrome, yet there is growing evidence stating that, under certain conditions, HE is associated with permanent neuronal injury and irreversibility. The pathophysiology of HE primarily implicates a strong role for hyperammonemia, but it is believed other pathogenic factors are involved. The fibrotic scarring of the liver during the progression of chronic liver disease (cirrhosis) consequently leads to increased hepatic resistance and circulatory anomalies characterized by portal hypertension, hyperdynamic circulatory state and systemic hypotension. The possible repercussions of these circulatory anomalies on brain perfusion, including impaired cerebral blood flow (CBF) autoregulation, could be implicated in the development of HE and/or permanent brain injury. Furthermore, hypotensive insults incurring during gastrointestinal bleed, infection, or liver transplantation may also trigger or exacerbate brain dysfunction and cell damage. This review will focus on the role of hypotension in the onset of HE as well as in the occurrence of neuronal cell loss in cirrhosis.
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Affiliation(s)
- Sydnée L'Écuyer
- Hepato-Neuro Laboratory, Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), 900, rue Saint-Denis - Pavillon R, R08.422 Montréal (Québec), Québec, H2X 0A9, Canada
| | - Emmanuel Charbonney
- Department of Medicine, Critical Care Division, Centre Hospitalier de l'Université de Montréal, Montréal, Canada
| | - François Martin Carrier
- Department of Medicine, Critical Care Division, Centre Hospitalier de l'Université de Montréal, Montréal, Canada
- Department of Anesthesiology, Centre Hospitalier de l'Université de Montréal, Montréal, Canada
- Carrefour de l'innovation et santé des populations , Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, Canada
| | - Christopher F Rose
- Hepato-Neuro Laboratory, Centre de recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), 900, rue Saint-Denis - Pavillon R, R08.422 Montréal (Québec), Québec, H2X 0A9, Canada.
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Heybe MA, Mehta KJ. Role of albumin infusion in cirrhosis-associated complications. Clin Exp Med 2024; 24:58. [PMID: 38551716 PMCID: PMC10980629 DOI: 10.1007/s10238-024-01315-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Accepted: 02/29/2024] [Indexed: 04/01/2024]
Abstract
Cirrhosis is an advanced-stage liver disease that occurs due to persistent physiological insults such as excessive alcohol consumption, infections, or toxicity. It is characterised by scar tissue formation, portal hypertension, and ascites (accumulation of fluid in the abdominal cavity) in decompensated cirrhosis. This review evaluates how albumin infusion ameliorates cirrhosis-associated complications. Since albumin is an oncotic plasma protein, albumin infusion allows movement of water into the intravascular space, aids with fluid resuscitation, and thereby contributes to resolving cirrhosis-induced hypovolemia (loss of extracellular fluid) seen in ascites. Thus, albumin infusion helps prevent paracentesis-induced circulatory dysfunction, a complication that occurs when treating ascites. When cirrhosis advances, other complications such as spontaneous bacterial peritonitis and hepatorenal syndrome can manifest. Infused albumin helps mitigate these by exhibiting plasma expansion, antioxidant, and anti-inflammatory functions. In hepatic encephalopathy, albumin infusion is thought to improve cognitive function by reducing ammonia concentration in blood and thereby tackle cirrhosis-induced hepatocyte malfunction in ammonia clearance. Infused albumin can also exhibit protective effects by binding to the cirrhosis-induced proinflammatory cytokines TNFα and IL6. While albumin administration has shown to prolong overall survival of cirrhotic patients with ascites in the ANSWER trial, the ATTIRE and MACHT trials have shown either no effect or limitations such as development of pulmonary oedema and multiorgan failure. Thus, albumin infusion is not a generic treatment option for all cirrhosis patients. Interestingly, cirrhosis-induced structural alterations in native albumin (which lead to formation of different albumin isoforms) can be used as prognostic biomarkers because specific albumin isoforms indicate certain complications of decompensated cirrhosis.
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Affiliation(s)
- Mohamed A Heybe
- GKT School of Medical Education, Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Kosha J Mehta
- Centre for Education, Faculty of Life Sciences and Medicine, King's College London, London, UK.
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Piccolo Serafim L, Simonetto DA, Choi DH, Weister TJ, Hanson AC, Kamath PS, Gajic O, Gallo de Moraes A. DERIVATION OF A MORTALITY PREDICTION MODEL IN CRITICAL CARE PATIENTS WITH CIRRHOSIS AND SEPSIS. Shock 2024; 61:382-386. [PMID: 38517233 DOI: 10.1097/shk.0000000000002323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/23/2024]
Abstract
ABSTRACT Objective : The aim of the study is to develop a predictive model for in-hospital mortality in critically ill patients with cirrhosis and sepsis, using clinical and laboratory data. Design : This is a retrospective cohort study. Setting: Medical and mixed intensive care units (ICUs) of a tertiary medical center. Patients : Cirrhotic adults were admitted with sepsis to the ICUs from January of 2007 to May of 2017. Interventions : None. Measurements and Main Results : Of 2,595 ICU admissions of patients with cirrhosis, 277 with first ICU admission for sepsis were included in the analysis, and 37% died in the hospital. Patients who stayed in the ICU for at least 6 h (n = 275) were considered for the multivariate model. Ten-fold cross-validation was used to estimate best parameter values and model performance, and the final model was chosen as the model maximizing area under the receiver-operating characteristic curve. Variables in order of impact were Acute Physiology and Chronic Health Evaluation (APACHE) III score, initial serum lactate, conjugated bilirubin, serum creatinine, model for end-stage liver disease score, age, body mass index, and serum hemoglobin. The final best model from cross-validation presented an area under the receiver operator characteristic curve (AUC) of 0.75, using a cut-point of 50% estimated probability, sensitivity and specificity were 0.46 and 0.90, respectively, with positive predictive value of 0.72 and negative predictive value of 0.74. These results were similar to the APACHE III only model (AUC = 0.74, sensitivity = 0.43, specificity = 0.89, positive predictive value = 0.69, negative predictive value = 0.73). Conclusion : The combination of initial serum lactate level, conjugated bilirubin, initial serum creatinine, model for end-stage liver disease score, age, body mass index, and serum hemoglobin did not yield meaningful improvement in the AUC and did not provide advantage over the APACHE III score for the prediction of in-hospital mortality in critically ill patients with cirrhosis and sepsis.
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Affiliation(s)
| | - Douglas A Simonetto
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | | | | | | | - Patrick S Kamath
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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Krznaric J, Papic N, Vrsaljko N, Gjurasin B, Kutlesa M, Vince A. Steatotic Liver Disease and Sepsis Outcomes-A Prospective Cohort Study (SepsisFAT). J Clin Med 2024; 13:798. [PMID: 38337491 PMCID: PMC10856507 DOI: 10.3390/jcm13030798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Revised: 01/25/2024] [Accepted: 01/27/2024] [Indexed: 02/12/2024] Open
Abstract
Background: While it has been shown that steatotic liver disease (SLD) is associated with systemic changes in immune response, the impact of SLD on sepsis outcomes has not yet been established. The aim of this study was to investigate the association between SLD and sepsis severity and outcomes. Methods: A prospective observational study included consecutively hospitalized adult patients with community-acquired sepsis during a 16-month period. Results: Of the 378 included patients (49.5% male, median age of 69, IQR 57-78 years), 174 (46%) were diagnosed with SLD. Patients with SLD were older and more frequently fulfilled the criteria for metabolic syndrome. There were no differences in the source and etiology of sepsis between the groups. Patients with SLD exhibited a higher incidence of acute kidney injury (29.3% vs. 17.6%), the need for renal replacement therapy (16.1% vs. 8.8%), and more frequent use of invasive mechanical ventilation (29.3% vs. 18.1%). In-hospital mortality was significantly higher in the SLD group (18.39% vs. 9.8%). The multivariable analysis indicated that SLD was associated with mortality (HR 2.82, 95% CI 1.40-5.71) irrespective of the other elements within metabolic syndrome. Conclusions: SLD might be associated with higher sepsis in-hospital mortality, and more frequent development of acute kidney and respiratory insufficiency requiring more critical care support.
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Affiliation(s)
- Juraj Krznaric
- Department of Infectology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia; (J.K.); (M.K.); (A.V.)
- Department for Adult Intensive Care and Neuroinfections, University Hospital for Infectious Diseases Zagreb, 10000 Zagreb, Croatia; (N.V.); (B.G.)
| | - Neven Papic
- Department of Infectology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia; (J.K.); (M.K.); (A.V.)
- Department for Viral Hepatitis, University Hospital for Infectious Diseases Zagreb, 10000 Zagreb, Croatia
| | - Nina Vrsaljko
- Department for Adult Intensive Care and Neuroinfections, University Hospital for Infectious Diseases Zagreb, 10000 Zagreb, Croatia; (N.V.); (B.G.)
| | - Branimir Gjurasin
- Department for Adult Intensive Care and Neuroinfections, University Hospital for Infectious Diseases Zagreb, 10000 Zagreb, Croatia; (N.V.); (B.G.)
| | - Marko Kutlesa
- Department of Infectology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia; (J.K.); (M.K.); (A.V.)
- Department for Adult Intensive Care and Neuroinfections, University Hospital for Infectious Diseases Zagreb, 10000 Zagreb, Croatia; (N.V.); (B.G.)
| | - Adriana Vince
- Department of Infectology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia; (J.K.); (M.K.); (A.V.)
- Department for Viral Hepatitis, University Hospital for Infectious Diseases Zagreb, 10000 Zagreb, Croatia
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Sbeit W, Maamoun B, Azzam S, Shahin A, Carmiel-Haggai M, Khoury T. Ascites fluid calprotectin level is highly accurate in diagnosing spontaneous bacterial peritonitis: a preliminary proof of concept prospective study. Clin Exp Med 2024; 24:25. [PMID: 38281236 PMCID: PMC10822801 DOI: 10.1007/s10238-023-01257-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Accepted: 12/15/2023] [Indexed: 01/30/2024]
Abstract
Ascites is the most common complication of liver cirrhosis. Spontaneous bacterial peritonitis (SBP) is a common complication of ascites. The diagnosis is made by an ascitic fluid polymorphonuclear (PMN) cell count of ≥ 250/mm3. However, no other diagnostic test is present for the diagnosis of SBP. The aim of the study present study is to assess the diagnostic yield of ascitic calprotectin in SBP, and to explore whether it can predict disease stage. We performed a single center proof-of-concept prospective study including all patients with cirrhosis and ascites who underwent paracentesis. Overall, 31 patients were included in the study. Eight patients had SBP vs. 23 patients without SBP. Ascitic calprotectin level was 77.4 ± 86.5 μg/mL in the SBP group, as compared to 16.1 ± 5.6 μg/mL in the non-SBP group (P = 0.001). An ascitic calprotectin cut-off value of > 21 μg/mL was associated with sensitivity and specificity of 85.7% and 89.5%, respectively, with ROC of 0.947 (95% CI 0.783 to 0.997, P < 0.0001). Notably, ascitic calprotectin did not had a prognostic value in cirrhosis stage and prognosis. Ascitic calprotectin was highly accurate in the diagnosis of SBP. It can be a serve as adjunct for indefinite cases of SBP.
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Affiliation(s)
- Wisam Sbeit
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, 1311502, Israel
| | - Basheer Maamoun
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, 1311502, Israel
| | - Subhi Azzam
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel
| | - Amir Shahin
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, 1311502, Israel
| | - Michal Carmiel-Haggai
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, 1311502, Israel
- Liver Unit, Galilee Medical Center, Nahariya, Israel
| | - Tawfik Khoury
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel.
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, 1311502, Israel.
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Ichita C, Shimizu S, Goto T, Haruki U, Itoh N, Iwagami M, Sasaki A. Effectiveness of antibiotic prophylaxis for acute esophageal variceal bleeding in patients with band ligation: A large observational study. World J Gastroenterol 2024; 30:238-251. [PMID: 38314133 PMCID: PMC10835525 DOI: 10.3748/wjg.v30.i3.238] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 12/12/2023] [Accepted: 01/03/2024] [Indexed: 01/18/2024] Open
Abstract
BACKGROUND Esophageal variceal bleeding is a severe complication associated with liver cirrhosis and typically necessitates endoscopic hemostasis. The current standard treatment is endoscopic variceal ligation (EVL), and Western guidelines recommend antibiotic prophylaxis following hemostasis. However, given the improvements in prognosis for variceal bleeding due to advancements in the management of bleeding and treatments of liver cirrhosis and the global concerns regarding the emergence of multidrug-resistant bacteria, there is a need to reassess the use of routine antibiotic prophylaxis after hemostasis. AIM To evaluate the effectiveness of antibiotic prophylaxis in patients treated for EVL. METHODS We conducted a 13-year observational study using the Tokushukai medical database across 46 hospitals. Patients were divided into the prophylaxis group (received antibiotics on admission or the next day) and the non-prophylaxis group (did not receive antibiotics within one day of admission). The primary outcome was composed of 6-wk mortality, 4-wk rebleeding, and 4-wk spontaneous bacterial peritonitis (SBP). The secondary outcomes were each individual result and in-hospital mortality. A logistic regression with inverse probability of treatment weighting was used. A subgroup analysis was conducted based on the Child-Pugh classification to determine its influence on the primary outcome measures, while sensitivity analyses for antibiotic type and duration were also performed. RESULTS Among 980 patients, 790 were included (prophylaxis: 232, non-prophylaxis: 558). Most patients were males under the age of 65 years with a median Child-Pugh score of 8. The composite primary outcomes occurred in 11.2% of patients in the prophylaxis group and 9.5% in the non-prophylaxis group. No significant differences in outcomes were observed between the groups (adjusted odds ratio, 1.11; 95% confidence interval, 0.61-1.99; P = 0.74). Individual outcomes such as 6-wk mortality, 4-wk rebleeding, 4-wk onset of SBP, and in-hospital mortality were not significantly different between the groups. The primary outcome did not differ between the Child-Pugh subgroups. Similar results were observed in the sensitivity analyses. CONCLUSION No significant benefit to antibiotic prophylaxis for esophageal variceal bleeding treated with EVL was detected in this study. Global reassessment of routine antibiotic prophylaxis is imperative.
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Affiliation(s)
- Chikamasa Ichita
- Gastroenterology Medicine Center, Shonan Kamakura General Hospital, Kamakura 247-8533, Kanagawa, Japan
- Department of Health Data Science, Yokohama City University, Yokohama 236-0027, Kanagawa, Japan
| | - Sayuri Shimizu
- Department of Health Data Science, Yokohama City University, Yokohama 236-0027, Kanagawa, Japan
| | - Tadahiro Goto
- Department of Health Data Science, Yokohama City University, Yokohama 236-0027, Kanagawa, Japan
- TXP Research, TXP Medical Co., Ltd., Chiyoda-ku 101-0042, Tokyo, Japan
- Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Bunkyo-ku 113-0033, Tokyo, Japan
| | - Uojima Haruki
- Gastroenterology Medicine Center, Shonan Kamakura General Hospital, Kamakura 247-8533, Kanagawa, Japan
- Department of Genome Medical Sciences Project, Research Institute, National Center for Global Health and Medicine, Ichikawa 272-8516, Chiba, Japan
| | - Naoya Itoh
- Division of Infectious Diseases, Aichi Cancer Center, Nagoya 464-8681, Aichi, Japan
| | - Masao Iwagami
- Department of Health Services Research, Institute of Medicine, University of Tsukuba, Tsukuba 305-8575, Ibaraki, Japan
| | - Akiko Sasaki
- Gastroenterology Medicine Center, Shonan Kamakura General Hospital, Kamakura 247-8533, Kanagawa, Japan
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Header DA, Ellakany WI, Ellakany AI. Fecal calprotectin level as a marker of esophageal varices in Egyptian HCV cirrhotic patients. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2023; 88:333-340. [PMID: 35810088 DOI: 10.1016/j.rgmxen.2022.06.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Accepted: 11/03/2021] [Indexed: 11/23/2022]
Abstract
INTRODUCTION AND AIM Esophageal varices are one of the complications of portal hypertension in cirrhotic patients that lead to high morbidity and mortality. Our aim was to assess the fecal calprotectin (FC) level in Egyptian cirrhotic patients as a non-invasive marker for the presence of esophageal varices. MATERIALS AND METHODS The current study included 250 participants in the period from June 2019 to November 2020, divided into three groups: group 1: 100 HCV cirrhotic patients with esophageal varices that would then be subdivided, according to the Paquet classification; group 2: 100 HCV cirrhotic patients without esophageal varices; group 3: 50 normal age and sex-matched healthy subjects as the control group. Patients with other causes of abnormal calprotectin results were excluded. RESULTS The comparison of FC in the three study groups revealed a statistically significant difference, with FC levels higher in groups 1 and 2 (mean 66.4±10.41 and 48.4±10.92, respectively). There was a significant difference in FC levels between the subgroups, subdivided according to the Paquet classification (P=.001). FC levels were higher in the grade III and IV subgroups. FC in the diagnosis of HCV cirrhotic patients with esophageal varices showed the best performance when the cut-off value was >55; AUC was 0.918, with 92% sensitivity, 95% specificity, and 93% accuracy. CONCLUSION FC levels serve as a screening tool for esophageal varices. FC was higher in cirrhotic patients with esophageal varices, especially in the grade III and IV subgroups, according to the Paquet classification.
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Affiliation(s)
- D A Header
- Departamento de Medicina Interna, Facultad de Medicina, Universidad de Alejandría, Alejandría, Egypt.
| | - W I Ellakany
- Departamento de Medicina Tropical, Facultad de Medicina, Universidad de Alejandría, Alejandría, Egypt
| | - A I Ellakany
- Departamento de Medicina Interna, Facultad de Medicina, Universidad de Alejandría, Alejandría, Egypt
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Janka T, Tornai D, Papp M, Vitális Z. The Value of Neutrophil-to-Lymphocyte Ratio to Identify Bacterial Infection and Predict Short-Term Mortality in Patients with Acutely Decompensated Cirrhosis. Diagnostics (Basel) 2023; 13:2954. [PMID: 37761321 PMCID: PMC10529351 DOI: 10.3390/diagnostics13182954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 08/29/2023] [Accepted: 09/12/2023] [Indexed: 09/29/2023] Open
Abstract
Liver cirrhosis patients are highly susceptible to infections, affecting survival, but current parameters for detecting infection are not reliable enough in this population. We investigated the ability of white blood cell (WBC), ∆WBC, neutrophil and ∆neutrophil counts, neutrophil-to-lymphocyte (NLR) and ∆NLR ratios and C-reactive protein (CRP) and procalcitonin (PCT) levels to identify infection and predict short-term mortality in liver cirrhosis patients. We recruited 233 patients with liver cirrhosis hospitalized with acute decompensation (AD) who had an outpatient visit within 1 month (baseline laboratory data) and followed them for 90 days. Difference between laboratory values at baseline and the AD episode was defined as delta (∆) values of the parameters. Delta values did not increase the diagnostic and predictive ability of investigated parameters. The CRP level was found to be the best diagnostic marker for infection in patients with cirrhosis. However, NLR seems to be superior for short-term mortality prediction, better than the WBC count. Distinguishing inflammations of different origin is a remaining clinical challenge in acutely decompensated cirrhosis. Based on our results, NLR might be more suitable for predicting short-term mortality in patients with AD than the WBC count currently included in the CLIF-C AD score.
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Affiliation(s)
- Tamás Janka
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary; (T.J.)
- Kálmán Laki Doctoral School of Biomedical and Clinical Sciences, University of Debrecen, 4032 Debrecen, Hungary
| | - Dávid Tornai
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary; (T.J.)
| | - Mária Papp
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary; (T.J.)
| | - Zsuzsanna Vitális
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary; (T.J.)
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Saner FH, Scarlatescu E, Broering DC, Bezinover D. The Yin and the Yang of Hemostasis in End-Stage Liver Disease. J Clin Med 2023; 12:5759. [PMID: 37685826 PMCID: PMC10488973 DOI: 10.3390/jcm12175759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 08/28/2023] [Accepted: 08/29/2023] [Indexed: 09/10/2023] Open
Abstract
Patients with end-stage liver disease (ESLD) undergoing liver transplantation (LT) are prone to thromboses both while on the waiting list and in the perioperative period. This hypercoagulability is associated with significant endothelial dysfunction (ED) due to nitric oxide dysregulation. ED and increased thrombin generation are the main factors responsible for this hypercoagulability. Sepsis alone can significantly alter a patient's coagulation profile. In combination with ESLD, however, sepsis or septic shock are responsible for very complex changes. This makes both the assessment and management of coagulation in septic patients with ESLD very challenging. Viscoelastic testing (VET) is the preferred method of coagulation management in patients with cirrhosis because, as with standard laboratory testing, VET can assess the entire coagulation system including the interaction between both pro- and anticoagulants and platelets.
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Affiliation(s)
- Fuat H. Saner
- King Faisal Specialist Hospital & Research Center, Organ Transplant Center of Excellence, Riyadh 11564, Saudi Arabia;
| | - Ecaterina Scarlatescu
- Department of Anesthesia and Intensive Care Medicine III, Fundeni Clinical Institute, 022328 Bucharest, Romania;
- Anesthesia and Intensive Care Department, University of Medicine and Pharmacy “Carol Davila”, 050474 Bucharest, Romania
| | - Dieter Clemens Broering
- King Faisal Specialist Hospital & Research Center, Organ Transplant Center of Excellence, Riyadh 11564, Saudi Arabia;
| | - Dmitri Bezinover
- Department of Anesthesiology and Critical Care, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA;
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Dawit L, Lee V, Lehoang D, Furey C, Chowdhury A, Mai TA, Angajala V, Park JH, Khadarian K, She R, Vergara-Lluri M, Kahn J, Dodge JL, Saito T. Clinical Significance of Ascitic Fluid Polymorphonuclear Leukocyte Percentage in Patients With Cirrhosis Without Spontaneous Bacterial Peritonitis. Clin Transl Gastroenterol 2023; 14:e00614. [PMID: 37436155 PMCID: PMC10522094 DOI: 10.14309/ctg.0000000000000614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Revised: 06/10/2023] [Accepted: 06/26/2023] [Indexed: 07/13/2023] Open
Abstract
INTRODUCTION Absolute polymorphonuclear leukocyte (PMN) count (PMN-C) ≥250 cells/mm 3 in ascites is the diagnostic hallmark of spontaneous bacterial peritonitis (SBP) and is associated with high morbidity and mortality. However, the clinical significance of ascitic PMN percentage (PMN-%) and PMN-C in the absence of SBP as additional biomarkers for mortality and future incidence of SBP has not been determined. METHODS This retrospective cohort included adults with cirrhosis undergoing first-recorded paracentesis with initial PMN-C < 250 cells/mm 3 at 2 tertiary medical centers between 2015 and 2020. Patients with prior SBP were excluded. Outcomes were death and SBP development. Cox regression estimated hazard ratios (HRs) for risk of death and SBP development and Akaike information criterion to compare model fit. RESULTS Three hundred eighty-four adults (73% male, median age 58 years, 67% with alcohol-associated cirrhosis, median PMN-C 14 cells/mm 3 [interquartile range 5-34], and median PMN-% 10% [interquartile range 4-20]) were included in this study. Univariate risk of death increased 10% per 25-unit increase in PMN-C (95% confidence interval 1.01-1.21, P = 0.03) and 19% per 10-unit increase in PMN-% (95% confidence interval 1.06-1.33, P = 0.003) with PMN-% demonstrating better model fit in assessing mortality risk (Akaike information criterion: 1,044 vs 1,048, respectively). In models adjusted for age, chronic hepatitis C virus infection, and Model for End-Stage Liver Disease-Sodium, PMN-% was associated with risk of death (PMN-% 10%-29%, HR 1.17, P = 0.50; PMN-% ≥ 30% group, HR 1.94, P = 0.03; vs PMN-% < 10%) and SBP development (PMN-% 10%-29%, HR 1.68, P = 0.07; PMN-% ≥ 30%, HR 3.48, P < 0.001; vs PMN-% < 10%). DISCUSSION Our results suggest PMN-% at first paracentesis represents a better biomarker compared with PMN-C for assessing risk of death and future SBP development in patients with PMN-C < 250 cells/mm 3 .
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Affiliation(s)
- Lillian Dawit
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Vivian Lee
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - David Lehoang
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Cameron Furey
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Aneesa Chowdhury
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Thu Anne Mai
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Varun Angajala
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Joo Hye Park
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Kevork Khadarian
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Rosemary She
- Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Maria Vergara-Lluri
- Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Jeffrey Kahn
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Jennifer L. Dodge
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
- USC Research Center for Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Takeshi Saito
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
- Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
- USC Research Center for Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
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Boustany A, Rahhal R, Onwuzo S, Almomani A, Boustany T, Kumar P, hitawala A, Asaad I. Cirrhotic patients on proton pump inhibitors are at a twofold risk of spontaneous bacterial peritonitis independently of gastrointestinal bleeding: a population-based retrospective study. Ann Gastroenterol 2023; 36:327-332. [PMID: 37144010 PMCID: PMC10152803 DOI: 10.20524/aog.2023.0794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Accepted: 01/30/2023] [Indexed: 05/06/2023] Open
Abstract
Background Recent findings suggest that cirrhotic patients on proton pump inhibitors (PPIs) are at a higher risk for developing spontaneous bacterial peritonitis (SBP) than non-PPI users. We aimed to identify whether PPI use is an independent risk factor for the development of SBP among cirrhotic patients in the United States (US). Methods We enrolled a retrospective cohort using a validated multicenter database. Patients with a SNOMED-CT diagnosis of "cirrhosis" between 1999 and 2022 were identified. All patients below 18 years of age were excluded. We calculated the prevalence of individuals using PPIs in the total US population and in cirrhotic patients from 1999 to date, and the incidence of SBP in the past year. Finally, we constructed a multivariate regression model, controlling for multiple covariates. Results The final analysis included 377,420 patients. The 20-year-period prevalence of SBP in patients with cirrhosis was 3.54% and the prevalence of patients using PPIs in the US population was 12,000 per 100,000 people (12.00%). The 1-year incidence of SBP in cirrhotic patients using PPIs was 2500 per 100,000 people. After accounting for confounders, the risk of SBP was higher among males, patients with a diagnosis of gastrointestinal bleeding, and those using β-blockers and PPIs. Conclusions To date, this is the largest cohort used to examine the prevalence of SBP among cirrhotic patients in the US. PPI use and hepatic encephalopathy offered the highest risk for the development of SBP, independently of gastrointestinal bleeding. Focusing on judicious PPI use should be encouraged among cirrhotic patients.
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Affiliation(s)
- Antoine Boustany
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA (Antoine Boustany, Somtochukwu Onwuzo, Ashraf Almomani, Prabhat Kumar, Imad Asaad)
| | - Romy Rahhal
- School of Medicine, Saint Joseph University of Beirut, Beirut, Lebanon (Romy Rahhal)
| | - Somtochukwu Onwuzo
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA (Antoine Boustany, Somtochukwu Onwuzo, Ashraf Almomani, Prabhat Kumar, Imad Asaad)
| | - Ashraf Almomani
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA (Antoine Boustany, Somtochukwu Onwuzo, Ashraf Almomani, Prabhat Kumar, Imad Asaad)
| | - Tara Boustany
- School of Pharmacy, University of Paris-Saclay, Paris, France (Tara Boustany)
| | - Prabhat Kumar
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA (Antoine Boustany, Somtochukwu Onwuzo, Ashraf Almomani, Prabhat Kumar, Imad Asaad)
| | - Asif hitawala
- Liver Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health, Bethesda, USA (Asif hitawala)
| | - Imad Asaad
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA (Antoine Boustany, Somtochukwu Onwuzo, Ashraf Almomani, Prabhat Kumar, Imad Asaad)
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Şehitoğlu MH, Öztopuz RÖ, Kılınç N, Ovalı MA, Büyük B, Gulcin İ. Thymol regulates the Endothelin-1 at gene expression and protein synthesis levels in septic rats. Chem Biol Interact 2023; 375:110426. [PMID: 36870466 DOI: 10.1016/j.cbi.2023.110426] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 01/24/2023] [Accepted: 02/26/2023] [Indexed: 03/06/2023]
Abstract
Sepsis is a serious systemic inflammatory response to infections. In this study, effects of thymol treatments on sepsis response were investigated. A total of 24 rats were randomly divided into 3 different treatment groups, namely as Control, Sepsis and Thymol. A sepsis model was created with a cecal ligation and perforation (CLP) in the sepsis group. For the treatment group, 100 mg/kg dose of thymol was administered via oral gavage and sepsis was established with a CLP after 1 h. All rats were sacrificed at 12 h post-opia. Blood and tissue samples were taken. ALT, AST, urea, creatinine and LDH were evaluated to assess the sepsis response in separated sera. Gene expression analysis was conducted for ET-1, TNF-α, IL-1 in lung, kidney and liver tissue samples. ET-1 and thymol interactions were determined by molecular docking studies. The ET-1, SOD, GSH-Px and MDA levels were determined by ELISA method. Genetic, biochemical and histopathological results were evaluated statistically. The pro-inflammatory cytokines and ET-1 gene expression revealed a significant decrease in the treatment groups, while there was an increase in septic groups. SOD, GSH-Px and MDA levels of rat tissues were significantly different in the thymol groups as compared to the sepsis groups (p < 0.05). Likewise, ET-1 levels were significantly reduced in the thymol groups. In terms of serum parameters, present findings were consistent with the literature. It was concluded based on present findings that thymol therapy may reduce sepsis-related morbidity, which would be beneficial in the early phase of the sepsis.
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Affiliation(s)
- Müşerref Hilal Şehitoğlu
- Department of Medical Biochemistry, Faculty of Medicine, Çanakkale Onsekiz Mart University, Çanakkale, Turkey
| | - Rahime Özlem Öztopuz
- Department of Biophysics, Faculty of Medicine, Çanakkale Onsekiz Mart University, Çanakkale, Turkey
| | - Namık Kılınç
- Department of Medical Services and Techniques, Vocational School of Higher Education for Healthcare Services, Iğdır University, Iğdır, Turkey
| | - Mehmet Akif Ovalı
- Department of Physiology, Faculty of Medicine, Çanakkale Onsekiz Mart University, Çanakkale, Turkey
| | - Başak Büyük
- Department of Histology and Embryology, Faculty of Medicine, İzmir Demokrasi University, İzmir, Turkey
| | - İlhami Gulcin
- Department of Chemistry, Faculty of Sciences, Atatürk University, Erzurum, Turkey.
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21
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Zhang Z, Wang J, Han W, Zhao L. Using machine learning methods to predict 28-day mortality in patients with hepatic encephalopathy. BMC Gastroenterol 2023; 23:111. [PMID: 37024814 PMCID: PMC10077693 DOI: 10.1186/s12876-023-02753-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Accepted: 03/29/2023] [Indexed: 04/08/2023] Open
Abstract
BACKGROUND Hepatic encephalopathy (HE) is associated with marked increases in morbidity and mortality for cirrhosis patients. This study aimed to develop and validate machine learning (ML) models to predict 28-day mortality for patients with HE. METHODS A retrospective cohort study was conducted in the Medical Information Mart for Intensive Care (MIMIC)-IV database. Patients from MIMIC-IV were randomized into training and validation cohorts in a ratio of 7:3. Training cohort was used for establishing the model while validation cohort was used for validation. The outcome was defined as 28-day mortality. Predictors were identified by recursive feature elimination (RFE) within 24 h of intensive care unit (ICU) admission. The area under the curve (AUC) and calibration curve were used to determine the predictive performance of different ML models. RESULTS In the MIMIC-IV database, 601 patients were eventually diagnosed with HE. Of these, 112 (18.64%) experienced death within 28 days. Acute physiology score III (APSIII), sepsis related organ failure assessment (SOFA), international normalized ratio (INR), total bilirubin (TBIL), albumin, blood urea nitrogen (BUN), acute kidney injury (AKI) and mechanical ventilation were identified as independent risk factors. Validation set indicated that the artificial neural network (NNET) model had the highest AUC of 0.837 (95% CI:0.774-0.901). Furthermore, in the calibration curve, the NNET model was also well-calibrated (P = 0.323), which means that it can better predict the 28-day mortality in HE patients. Additionally, the performance of the NNET is superior to existing scores, including Model for End-Stage Liver Disease (MELD) and Model for End-Stage Liver Disease-Sodium (MELD-Na). CONCLUSIONS In this study, the NNET model demonstrated better discrimination in predicting 28-day mortality as compared to other models. This developed model could potentially improve the early detection of HE with high mortality, subsequently improving clinical outcomes in these patients with HE, but further external prospective validation is still required.
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Affiliation(s)
- Zhe Zhang
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, No. 1 Xinsi Road, Xi'an, 710038, China
| | - Jian Wang
- Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, No. 1 Xinsi Road, Xi'an, China
| | - Wei Han
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, No. 1 Xinsi Road, Xi'an, 710038, China
| | - Li Zhao
- Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, No. 1 Xinsi Road, Xi'an, 710038, China.
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22
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Miao H, Cui Z, Guo Z, Chen Q, Su W, Sun Y, Sun M, Ma X, Ding R. IDENTIFICATION OF SUBPHENOTYPES OF SEPSIS-ASSOCIATED LIVER DYSFUNCTION USING CLUSTER ANALYSIS. Shock 2023; 59:368-374. [PMID: 36562264 DOI: 10.1097/shk.0000000000002068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
ABSTRACT Objectives: We attempted to identify and validate the subphenotypes of sepsis-associated liver dysfunction (SALD) using routine clinical information. Design: This article is a retrospective observational cohort study. Setting: We used the Medical Information Mart for Intensive Care IV database and the eICU Collaborative Research Database. Patients: We included adult patients (age ≥18 years) who developed SALD within the first 48 hours of intensive care unit (ICU) admission. We excluded patients who died or were discharged from the ICU within the first 48 hours of admission. Patients with abnormal liver function before ICU admission were also excluded. Measurements and Main Results: Patients in the MIMIC-IV 1.0 database served as a derivation cohort. Patients in the eICU database were used as validation cohort. We identified four subphenotypes of SALD (subphenotype α, β, γ, δ) using K-means cluster analysis in 5234 patients in derivation cohort. The baseline characteristics and clinical outcomes were compared between the phenotypes using one-way analysis of variance/Kruskal-Wallis test and the χ 2 test. Moreover, we used line charts to illustrate the trend of liver function parameters over 14 days after ICU admission. Subphenotype α (n = 1,055) was the most severe cluster, characterized by shock with multiple organ dysfunction (MODS) group. Subphenotype β (n = 1,179) had the highest median bilirubin level and the highest proportion of patients with underlying liver disease and coexisting coagulopathy (increased bilirubin group). Subphenotype γ (n = 1,661) was the cluster with the highest mean age and had the highest proportion of patients with chronic kidney disease (aged group). Subphenotype δ (n = 1,683) had the lowest 28-day and in-hospital mortality (mild group). The characteristics of clusters in the validation cohort were similar to those in the derivation cohort. In addition, we were surprised to find that GGT levels in subphenotype δ were significantly higher than in other subphenotypes, showing a different pattern from bilirubin. Conclusions: We identified four subphenotypes of SALD that presented with different clinical features and outcomes. These results can provide a valuable reference for understanding the clinical characteristics and associated outcomes to improve the management of patients with SALD in the ICU.
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Affiliation(s)
- He Miao
- Department of Intensive Care Unit, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Zhigang Cui
- School of Nursing, China Medical University, Shenyang, Liaoning Province, China
| | - Zhaotian Guo
- Department of Intensive Care Unit, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Qianhui Chen
- Department of Intensive Care Unit, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Wantin Su
- Department of Intensive Care Unit, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Yongqiang Sun
- Neusoft Corporation, Shenyang, Liaoning Province, China
| | - Mu Sun
- Neusoft Corporation, Shenyang, Liaoning Province, China
| | - Xiaochun Ma
- Department of Intensive Care Unit, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
| | - Renyu Ding
- Department of Intensive Care Unit, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
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23
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Kim RW, Raghunathan K, Martin GS, Davis EA, Sindhwani NS, Telang S, Lodaya K. Timely Albumin Improves Survival in Patients With Cirrhosis on Diuretic Therapy Who Develop Acute Kidney Injury: Real-World Evidence in the United States. GASTRO HEP ADVANCES 2022; 2:252-260. [PMID: 39132612 PMCID: PMC11307587 DOI: 10.1016/j.gastha.2022.10.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 10/19/2022] [Indexed: 08/13/2024]
Abstract
Background and Aims Patients admitted with decompensated cirrhosis who develop acute kidney injury (AKI) tend to experience poor outcomes, even if provided with increased organ support such as renal replacement therapies. We assessed the association of albumin administered ≤24 hours of admission with hospital length of stay (LOS) and in-hospital mortality. Methods The Cerner Health Facts Database was queried for hospitalized patients with cirrhosis who had >0.3 mg/dL increase in serum creatinine within 48 hours and received diuretics following admission between January 2009 and April 2018. This study received institutional review board exemption through federal regulation 45CFR46. Albumin infusion was "timely" if administered ≤24 hours after admission and "nontimely" if administered >24 hours after admission or not at all. Two subgroups were assessed: the AKILOS subgroup (patients who survived to discharge) and the AKIMORTALITY RISK subgroup (patients with the highest risk of mortality, ie, AKI stage 3). Results A total of 4135 hospitalizations with cirrhosis and AKI were grouped into AKILOS (n = 3321) and AKIMORTALITY RISK (n = 609) subgroups. Albumin administration occurred in 59.7% of the AKILOS subgroup and 77.8% of the AKIMORTALITY RISK subgroup, but timely treatment only occurred in 25.9% and 35.8% of encounters within these subgroups, respectively. Risk-adjusted analysis showed timely albumin administration to be associated with a 15.5% reduction (P < .01) in LOS in the AKILOS subgroup and a 49% reduction in the odds of death (adjusted odds ratio: 0.51; P < .01) in the AKIMORTALITY RISK subgroup, when compared to the nontimely group. Conclusion Among patients with cirrhosis and AKI, treatment with albumin ≤24 hours after admission was associated with a shorter LOS and lower risk of death in patients with stage 3 AKI.
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Affiliation(s)
- Ray W. Kim
- Division of Gastroenterology and Hepatology, Stanford University, Stanford, California
| | | | - Greg S. Martin
- Department of Medicine, Emory University, Atlanta, Georgia
| | - E. Anne Davis
- Grifols Shared Services North America (SSNA), Research Triangle Park, North Carolina
| | - Navreet S. Sindhwani
- Grifols Shared Services North America (SSNA), Research Triangle Park, North Carolina
| | | | - Kunal Lodaya
- Boston Strategic Partners, Inc, Boston, Massachusetts
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Lotte R, Courdurié A, Gaudart A, Emery A, Chevalier A, Tran A, Payen M, Ruimy R. Spontaneous Bacterial Peritonitis: The Incremental Value of a Fast and Direct Bacterial Identification from Ascitic Fluids Inoculated in Blood Culture Bottles by MALDI-TOF MS for a Better Management of Patients. Microorganisms 2022; 10:microorganisms10061188. [PMID: 35744706 PMCID: PMC9228703 DOI: 10.3390/microorganisms10061188] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 06/02/2022] [Accepted: 06/04/2022] [Indexed: 11/24/2022] Open
Abstract
Spontaneous bacterial peritonitis (SBP) is a severe infection that requires fast and accurate antibiotic therapy to improve the patient outcome. Direct bacterial identification using MALDI-TOF mass spectrometry from ascitic fluid inoculated in blood culture bottles (BCBs) could therefore improve patients’ management. We evaluated the impact of the implementation of this method for the treatment of patients. Our identification protocol was performed on 136 positive BCBs collected from 61 patients between December 2018 and December 2020. The therapeutic impact of our protocol was evaluated using a before (2015–2016) and after (2019–2020) case–control study in two populations of 41 patients diagnosed with SBP and treated with antibiotics. The decrease in time to first identification and the optimization of antibiotic therapy following communication of the identification result were evaluated. Our protocol allowed us to identify 78% of bacteria in ascitic fluids. The transmission of the direct identification allowed the introduction or adaption of the antibiotic therapy early in 37% of SBP, with a mean decrease in time to first antibiotic change of 17 h. Our direct identification protocol for positive inoculated ascitic fluids is fast, reliable and inexpensive. Its routine integration into a microbiology laboratory allows the early introduction of appropriate antibiotic therapy and improves the management of patients with SBP.
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Affiliation(s)
- Romain Lotte
- Laboratory of Bacteriology, Centre Hospitalier Universitaire de Nice, 06200 Nice, France; (A.G.); (A.E.); (A.C.); (M.P.); (R.R.)
- Université Côte d’Azur, Centre Hospitalier Universitaire de Nice, 06000 Nice, France;
- Université Côte d’Azur, Inserm, C3M, 06200 Nice, France
- Correspondence: ; Tel.: +33-(0)49-203-6218
| | - Audrey Courdurié
- Infectious Diseases Department, Centre Hospitalier Universitaire de Nice, 06200 Nice, France;
| | - Alice Gaudart
- Laboratory of Bacteriology, Centre Hospitalier Universitaire de Nice, 06200 Nice, France; (A.G.); (A.E.); (A.C.); (M.P.); (R.R.)
| | - Audrey Emery
- Laboratory of Bacteriology, Centre Hospitalier Universitaire de Nice, 06200 Nice, France; (A.G.); (A.E.); (A.C.); (M.P.); (R.R.)
| | - Alicia Chevalier
- Laboratory of Bacteriology, Centre Hospitalier Universitaire de Nice, 06200 Nice, France; (A.G.); (A.E.); (A.C.); (M.P.); (R.R.)
- Université Côte d’Azur, Centre Hospitalier Universitaire de Nice, 06000 Nice, France;
- Université Côte d’Azur, Inserm, C3M, 06200 Nice, France
| | - Albert Tran
- Université Côte d’Azur, Centre Hospitalier Universitaire de Nice, 06000 Nice, France;
- Université Côte d’Azur, Inserm, C3M, 06200 Nice, France
- Hepatology Department, Centre Hospitalier Universitaire de Nice, 06200 Nice, France
| | - Mathilde Payen
- Laboratory of Bacteriology, Centre Hospitalier Universitaire de Nice, 06200 Nice, France; (A.G.); (A.E.); (A.C.); (M.P.); (R.R.)
- Université Côte d’Azur, Centre Hospitalier Universitaire de Nice, 06000 Nice, France;
- Université Côte d’Azur, Inserm, C3M, 06200 Nice, France
| | - Raymond Ruimy
- Laboratory of Bacteriology, Centre Hospitalier Universitaire de Nice, 06200 Nice, France; (A.G.); (A.E.); (A.C.); (M.P.); (R.R.)
- Université Côte d’Azur, Centre Hospitalier Universitaire de Nice, 06000 Nice, France;
- Université Côte d’Azur, Inserm, C3M, 06200 Nice, France
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25
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Khamri W, Gudd C, Liu T, Nathwani R, Krasniqi M, Azam S, Barbera T, Trovato FM, Possamai L, Triantafyllou E, Seoane RC, Lebosse F, Singanayagam A, Kumar N, Bernsmeier C, Mukherjee S, McPhail M, Weston CJ, Antoniades CG, Thursz MR. Suppressor CD4 + T cells expressing HLA-G are expanded in the peripheral blood from patients with acute decompensation of cirrhosis. Gut 2022; 71:1192-1202. [PMID: 34344786 PMCID: PMC9120410 DOI: 10.1136/gutjnl-2021-324071] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Accepted: 07/22/2021] [Indexed: 12/08/2022]
Abstract
OBJECTIVE Identifying components of immuneparesis, a hallmark of chronic liver failure, is crucial for our understanding of complications in cirrhosis. Various suppressor CD4+ T cells have been established as potent inhibitors of systemic immune activation. Here, we establish the presence, regulation and mechanism of action of a suppressive CD4+ T cell subset expressing human leucocyte antigen G (HLA-G) in patients with acute decompensation of cirrhosis (AD). DESIGN Flow cytometry was used to determine the proportion and immunophenotype of CD4+HLA-G+ T cells from peripheral blood of 20 healthy controls (HCs) and 98 patients with cirrhosis (28 with stable cirrhosis (SC), 20 with chronic decompensated cirrhosis (CD) and 50 with AD). Transcriptional and functional signatures of cell-sorted CD4+HLA-G+ cells were delineated by NanoString technology and suppression assays, respectively. The role of immunosuppressive cytokine interleukin (IL)-35 in inducing this population was investigated through in vitro blockade experiments. Immunohistochemistry (IHC) and cultures of primary human Kupffer cells (KCs) were performed to assess cellular sources of IL-35. HLA-G-mediated T cell suppression was explored using neutralising antibodies targeting co-inhibitory pathways. RESULTS Patients with AD were distinguished by an expansion of a CD4+HLA-G+CTLA-4+IL-35+ immunosuppressive population associated with disease severity, clinical course of AD, infectious complications and poor outcome. Transcriptomic analyses excluded the possibility that these were thymic-derived regulatory T cells. IHC analyses and in vitro cultures demonstrate that KCs represent a potent source of IL-35 which can induce the observed HLA-G+ phenotype. These exert cytotoxic T lymphocyte antigen-4-mediated impaired responses in T cells paralleled by an HLA-G-driven downregulation of T helper 17-related cytokines. CONCLUSION We have identified a cytokine-driven peripherally derived suppressive population that may contribute to immuneparesis in AD.
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Affiliation(s)
- Wafa Khamri
- Section of Hepatology & Gastroenterology, Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK
| | - Cathrin Gudd
- Section of Hepatology & Gastroenterology, Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK
| | - Tong Liu
- Section of Hepatology & Gastroenterology, Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK
| | - Rooshi Nathwani
- Section of Hepatology & Gastroenterology, Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK
| | - Marigona Krasniqi
- Section of Hepatology & Gastroenterology, Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK
| | - Sofia Azam
- Section of Hepatology & Gastroenterology, Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK
| | - Thomas Barbera
- Section of Hepatology & Gastroenterology, Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK
| | - Francesca M Trovato
- Department of Inflammation Biology, Institute of Liver Studies, King’s College London, London, UK
| | - Lucia Possamai
- Section of Hepatology & Gastroenterology, Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK
| | - Evangelos Triantafyllou
- Section of Hepatology & Gastroenterology, Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK
| | - Rocio Castro Seoane
- Section of Hepatology & Gastroenterology, Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK
| | - Fanny Lebosse
- Section of Hepatology & Gastroenterology, Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK
| | - Arjuna Singanayagam
- Section of Hepatology & Gastroenterology, Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK
| | - Naveenta Kumar
- Section of Hepatology & Gastroenterology, Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK
| | - Christine Bernsmeier
- Section of Hepatology & Gastroenterology, Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK,Department of Inflammation Biology, Institute of Liver Studies, King’s College London, London, UK
| | - Sujit Mukherjee
- Section of Hepatology & Gastroenterology, Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK
| | - Mark McPhail
- Department of Inflammation Biology, Institute of Liver Studies, King’s College London, London, UK
| | - Chris J Weston
- NIHR Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK
| | - Charalambos Gustav Antoniades
- Section of Hepatology & Gastroenterology, Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK
| | - Mark R Thursz
- Section of Hepatology & Gastroenterology, Division of Digestive Diseases, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK
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26
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Choudry N, Sasso R, Rockey DC. Infection in Hospitalized Cirrhosis Patients: Changing Epidemiology and Clinical Features. Am J Med Sci 2022; 363:114-121. [PMID: 34995572 DOI: 10.1016/j.amjms.2021.10.023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 06/29/2021] [Accepted: 10/21/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND Patients with cirrhosis are uniquely predisposed to infections, which can lead to acute decompensation and an increase in mortality rates. We hypothesized that not only are cirrhotic patients more likely to develop certain infections, but that specific infections are associated with poorer outcomes. Therefore, we aimed to examine the epidemiology, bacteriology, and outcomes of infections in cirrhotic patients admitted to the hospital. METHODS In this single center observational retrospective cohort study, we identified admissions in which patients had an infection from a group of all admissions of cirrhotics from 2011-2016. Infections were categorized by the primary source of infection, and rigorous clinical and bacteriologic definitions were used. RESULTS We identified 1,208 admissions in 877 unique patients during the study period. The most common infections identified were as follows: urinary tract infections (33%), pneumonia (23%), spontaneous bacterial peritonitis (14%), and bacteremia (11%). Gram-positive organisms were most commonly isolated in patients with spontaneous bacterial peritonitis and bacteremia, whereas gram-negative bacteria were most prevalent in urinary tract infections and pneumonia. Candida infections were common and identified in the following proportions: spontaneous bacterial peritonitis (16%), pneumonia (14%), bacteremia (13%), and urinary tract infections (9%). Pneumonia, spontaneous bacterial peritonitis, and meningitis were associated with increased mortality rates (29%, 32%, and 67%, respectively), compared to the overall mortality rate of 20% (p-value < 0.05). CONCLUSIONS In summary, infections were common in patients with cirrhosis and were associated with poor outcomes, particularly in the presence of evidence of sepsis. Spontaneous bacterial peritonitis and bacteremia are now most commonly due to gram-positive organisms and fungal infections appear to be rising in prevalence.
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Affiliation(s)
- Nida Choudry
- Division of Gastroenterology and Hepatology, and the Digestive Disease Research Center, Medical University of South Carolina, Charleston, South Carolina
| | - Roula Sasso
- Division of Gastroenterology and Hepatology, and the Digestive Disease Research Center, Medical University of South Carolina, Charleston, South Carolina
| | - Don C Rockey
- Division of Gastroenterology and Hepatology, and the Digestive Disease Research Center, Medical University of South Carolina, Charleston, South Carolina.
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27
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Choi C, Choi DH, Spears GM, Peeraphatdit TB, Serafim LP, Gajic O, Kamath PS, Shah VH, Gallo de Moraes A, Simonetto DA. Relationship Between Etiology of Cirrhosis and Survival Among Patients Hospitalized in Intensive Care Units. Mayo Clin Proc 2022; 97:274-284. [PMID: 35090753 PMCID: PMC8883528 DOI: 10.1016/j.mayocp.2021.08.025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 05/25/2021] [Accepted: 08/06/2021] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To determine short-term outcomes of patients with alcohol-associated cirrhosis (ALC) admitted to the intensive care unit (ICU) compared with other etiologies of liver disease. In addition, we investigate whether quick sequential organ failure assessment accurately predicts presence of sepsis and in-hospital mortality in critically ill patients with various etiologies of cirrhosis. METHODS A retrospective cohort of 1174 consecutive patients with cirrhosis admitted to the ICU between January of 2006 and December of 2015 was analyzed. Outcomes of interest included survival rates within the ICU, post-ICU in-hospital, or at 30 days post-ICU discharge. RESULTS Five hundred seventy-eight patients were found to have ALC with 596 in the non-ALC group. There was no significant difference in ICU mortality rates in ALC versus non-ALC cohorts (10.2% vs 11.7%, P=.40). However, patients with ALC had significantly higher post-ICU in-hospital death (10.0% vs 6.5%, P=.04) as well as higher mortality at 30-day post-ICU discharge (18.7% vs 11.2%, P<.001). Sustained alcohol abstinence did not offer survival advantage over nonabstinence. The predictive power for quick sequential organ failure assessment for sepsis and in-hospital mortality for patients with cirrhosis was limited. CONCLUSION Critically ill patients with ALC have decreased survival after ICU discharge compared with patients with other etiologies of cirrhosis, independent of alcohol abstinence.
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Affiliation(s)
- Chansong Choi
- Department of Internal Medicine, Mayo Clinic, Rochester, MN
| | - Dae Hee Choi
- Department of Internal Medicine, School of Medicine, Kangwon National University, Republic of Korea
| | - Grant M Spears
- Department of Health Sciences Research, Mayo Clinic, Rochester, MN
| | - Thoetchai Bee Peeraphatdit
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN
| | - Laura Piccolo Serafim
- Department of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN; Multidisciplinary Epidemiology and Translational Research in Intensive Care (METRIC), Mayo Clinic, Rochester, MN
| | - Ognjen Gajic
- Department of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN; Multidisciplinary Epidemiology and Translational Research in Intensive Care (METRIC), Mayo Clinic, Rochester, MN
| | - Patrick S Kamath
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN
| | - Vijay H Shah
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN
| | - Alice Gallo de Moraes
- Department of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN; Multidisciplinary Epidemiology and Translational Research in Intensive Care (METRIC), Mayo Clinic, Rochester, MN
| | - Douglas A Simonetto
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN.
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28
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Al Sulaiman K, Kharbosh A, Bin Salah K, Alsulaiman T, Al Andas N, Aljuhani O, Vishwakarma R. Impact of Ursodeoxycholic Acid in Critically Ill Patients With Sepsis: A Retrospective Study. J Pharm Pract 2022; 36:566-571. [PMID: 37189247 DOI: 10.1177/08971900211038363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background: Using ursodeoxycholic acid (UDCA) in critically ill patients as adjunctive therapy for sepsis/septic shock in neonates and children is controversial, while it has not been extensively investigated in adults. This study aims to assess the effect of UDCA use on the early resolution of sepsis/septic shock in critically ill adult patients. Method: A retrospective study of critically ill adult patients in the intensive care unit (ICU) admitted with sepsis/septic shock at King Abdulaziz Medical City. Based on their usage of UDCA, patients were categorized into two groups. A total of 88 patients were included for analysis after matching, based on severity of illness scores within 24-hours of ICU admission. The primary outcome was to assess the effect of UDCA on the severity and resolution of shock at day three of ICU admission. The secondary outcomes were 30-day in-hospital mortality, mechanical ventilation (MV) duration, and ICU length of stay (LOS). Results: Out of the 88 patients matched, 44 patients (50%) received UDCA during the study period. Using UDCA was neither associated with improvement in Sequential Organ Failure Assessment (SOFA) score ( p-value: 0.32), inotropes/vasopressors requirement ( p-value: 0.79), Glasgow Coma Scale (GCS) ( p-value: 0.59) nor total bilirubin levels ( p-value: 0.79) at day three compared with the control. There was a significant association between using UDCA and improvement in PaO2/FiO2 ratio ( p-value: 0.01) and early extubation at day three ( p-value: 0.04). Conclusion: Using UDCA in critically ill patients with sepsis/septic shock was not associated with improvement in shock severity and resolution. However, patients who received UDCA were more likely to be extubated and not require MV on day three of ICU admission.
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Affiliation(s)
- Khalid Al Sulaiman
- Pharmaceutical Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
| | - Abdullah Kharbosh
- Clinical Pharmacy Department, Pharmacy College, Taif University, Taif, Saudi Arabia
| | - Khalid Bin Salah
- Pharmaceutical Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
| | - Thamer Alsulaiman
- Family Medicine Department, King Faisal Specialist Hospital and Research Centre (KFSH&RC), Riyadh, Saudi Arabia
| | - Norah Al Andas
- Pharmaceutical Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia
| | - Ohoud Aljuhani
- Faculty of Pharmacy, Department of Pharmacy Practice, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Ramesh Vishwakarma
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
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Praharaj DL, Premkumar M, Roy A, Verma N, Taneja S, Duseja A, Dhiman RK. Rifaximin Vs. Norfloxacin for Spontaneous Bacterial Peritonitis Prophylaxis: A Randomized Controlled Trial. J Clin Exp Hepatol 2022; 12:336-342. [PMID: 35535057 PMCID: PMC9077172 DOI: 10.1016/j.jceh.2021.08.010] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 08/12/2021] [Indexed: 12/13/2022] Open
Abstract
Background Spontaneous bacterial peritonitis (SBP) heralds increased mortality in cirrhosis, mandating strategies for prophylaxis. Norfloxacin has been the recommended choice for SBP prevention. However, its use has raised concerns about antibiotic resistance. Rifaximin has been suggested as an alternative. We investigated the efficacy of rifaximin against norfloxacin in primary and secondary prophylaxis of SBP. Methods In this open-labeled randomized trial, patients with either advanced cirrhosis having ascitic fluid protein levels (<1.5 g/l), Child-Pugh score ≥9 points, serum bilirubin ≥3 mg/dl or impaired renal function (primary prophylaxis group), or those with prior SBP (secondary prophylaxis group) received either norfloxacin (400 mg once daily) or rifaximin (550 mg twice daily). All patients were followed for six months, with the primary endpoint being the development of incident SBP. Results 142 patients were assessed for eligibility, of which 132 met the enrolment criteria; 12 were lost to follow-up, while 4 discontinued treatment. In patients on primary prophylaxis, occurrence of SBP was similar (14.3% vs. 24.3%, P = 0.5), whereas in secondary prophylaxis SBP recurrence was lower with rifaximin (7% vs. 39% P = 0.004). Rifaximin significantly reduced the odds for SBP development in secondary prophylaxis [OR (95% CI0.14 (0.02-0.73; P = 0.02)]. Patients receiving rifaximin as secondary prophylaxis also had fewer episodes of hepatic encephalopathy (23.1% vs. 51.5%, P = 0.02). 180-day survival between the arms in either group was similar (P = 0.5, P = 0.2). Conclusion In comparison to norfloxacin, rifaximin significantly reduces incident events of SBP, as well as HE when used as a secondary prophylaxis, whereas for primary prophylaxis both have similar effects (NCT03695705). Clinical trial registration ClinicalTrials.gov number: NCT03695705.
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Key Words
- ACLF, Acute on chronic liver failure
- AKI, Acute Kidney Injury
- CONSORT, Consolidated Standards of Reporting Trials
- CTP, Child-Turcotte-Pugh
- HE, Hepatic encephalopathy
- HRS, Hepatorenal syndrome
- MELD, Model of end-stage liver disease
- SAAG, Serum ascites albumin gradient
- SBP
- SBP, Spontaneous bacterial peritonitis
- UGIB, Upper Gastrointestinal Bleed
- VH, Variceal hemorrhage
- antibiotic
- ascites
- cirrhosis
- hepatic encephalopathy
- infection
- primary
- resistance
- secondary
- survival
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Affiliation(s)
- Dibya L. Praharaj
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Madhumita Premkumar
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Akash Roy
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India,Department of Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India
| | - Nipun Verma
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Sunil Taneja
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Ajay Duseja
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Radha K. Dhiman
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India,Department of Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India,Address for correspondence. Prof Radha K Dhiman, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebarelly Road, Lucknow, 226014, India. Tel.: +917087009337 (mobile).
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Zoratti C, Moretti R, Rebuzzi L, Albergati IV, Di Somma A, Decorti G, Di Bella S, Crocè LS, Giuffrè M. Antibiotics and Liver Cirrhosis: What the Physicians Need to Know. Antibiotics (Basel) 2021; 11:31. [PMID: 35052907 PMCID: PMC8772826 DOI: 10.3390/antibiotics11010031] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 12/23/2021] [Accepted: 12/24/2021] [Indexed: 12/13/2022] Open
Abstract
The liver is the primary site of drug metabolism, which can be altered by a variety of diseases affecting the liver parenchyma, especially in patients with liver cirrhosis. The use of antibiotics in patients with cirrhosis is usually a matter of concern for physicians, given the lack of practical knowledge for drug choice and eventual dose adjustments in several clinical scenarios. The aim of the current narrative review is to report, as broadly as possible, basic, and practical knowledge that any physician should have when approaching a patient with liver cirrhosis and an ongoing infection to efficiently choose the best antibiotic therapy.
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Affiliation(s)
- Caterina Zoratti
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (C.Z.); (R.M.); (L.R.); (I.V.A.); (A.D.S.); (S.D.B.); (L.S.C.)
| | - Rita Moretti
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (C.Z.); (R.M.); (L.R.); (I.V.A.); (A.D.S.); (S.D.B.); (L.S.C.)
| | - Lisa Rebuzzi
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (C.Z.); (R.M.); (L.R.); (I.V.A.); (A.D.S.); (S.D.B.); (L.S.C.)
| | - Irma Valeria Albergati
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (C.Z.); (R.M.); (L.R.); (I.V.A.); (A.D.S.); (S.D.B.); (L.S.C.)
| | - Antonietta Di Somma
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (C.Z.); (R.M.); (L.R.); (I.V.A.); (A.D.S.); (S.D.B.); (L.S.C.)
| | - Giuliana Decorti
- Institute for Maternal and Child Health-IRCCS Burlo Garofolo, 34137 Trieste, Italy;
| | - Stefano Di Bella
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (C.Z.); (R.M.); (L.R.); (I.V.A.); (A.D.S.); (S.D.B.); (L.S.C.)
| | - Lory Saveria Crocè
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (C.Z.); (R.M.); (L.R.); (I.V.A.); (A.D.S.); (S.D.B.); (L.S.C.)
- Italian Liver Foundation, 34149 Trieste, Italy
| | - Mauro Giuffrè
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy; (C.Z.); (R.M.); (L.R.); (I.V.A.); (A.D.S.); (S.D.B.); (L.S.C.)
- Italian Liver Foundation, 34149 Trieste, Italy
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Trends and outcomes of infective endocarditis in cirrhosis: a propensity-matched national study. Eur J Gastroenterol Hepatol 2021; 33:e580-e586. [PMID: 35048650 DOI: 10.1097/meg.0000000000002177] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND Cirrhosis is the most common cause of liver-related death and bacterial infection is a common comorbidity in cirrhosis. We aimed to study the trends and outcomes of infective endocarditis in cirrhosis. METHODS A propensity-matched analysis of the National Inpatient Sample database was performed to assess outcomes of infective endocarditis in adult patients (>18 years) from 2004-2013 with and without cirrhosis. Various outcomes were assessed for outcomes of infective endocarditis in cirrhosis. Multivariate regression analysis was performed for predictors of mortality in infective endocarditis. RESULTS There has been no significant change in incidence (3.3-3.6%, P = 0.27) and overall mortality (6.3-8.6%, P = 0.42) of infective endocarditis in cirrhosis. After propensity matching, patients with cirrhosis had significantly higher in-hospital mortality (15 vs. 10.6%, P < 0.001) and acute kidney injury (AKI) (31.8 vs. 28.5%, P < 0.001) as compared to no cirrhosis. Microbiological analysis revealed significantly higher rates of streptococci (35.3 vs. 31.9%, P < 0.001) and fungal infective endocarditis (0.03 vs. 0%, P < 0.001) and lower incidence of Gram-negative infective endocarditis (3.9 vs. 6.3%, P < 0.001) in cirrhosis. Cirrhosis patients had significantly less surgical intervention (10.2 vs. 30.3%, P < 0.001) along with overall total cost and length of stay as compared to no cirrhosis. On multivariate analysis, advanced age, AKI, shock and mechanical ventilation were positive predictors of mortality in infective endocarditis patients with cirrhosis patients. CONCLUSIONS Cirrhosis is an independent predictor of mortality in infective endocarditis with worse outcomes and less surgical intervention. Gram-negative infective endocarditis is lower in cirrhosis, whereas streptococci and fungal infective endocarditis are higher than noncirrhotic patients.
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Tornai D, Vitalis Z, Jonas A, Janka T, Foldi I, Tornai T, Sipeki N, Csillag A, Balogh B, Sumegi A, Foldesi R, Papp M, Antal-Szalmas P. Increased sTREM-1 levels identify cirrhotic patients with bacterial infection and predict their 90-day mortality. Clin Res Hepatol Gastroenterol 2021; 45:101579. [PMID: 33773436 DOI: 10.1016/j.clinre.2020.11.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2020] [Revised: 10/06/2020] [Accepted: 11/06/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Patients with cirrhosis are susceptible to bacterial infections (BIs) that are major causes of specific complications and mortality. However, the diagnosis of BIs can often be difficult in advanced disease stage since their symptoms may overlap with the ones of acute decompensation (AD). Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is released from monocytes/macrophages and neutrophils during activation and has been reported to correlate with activity of various inflammatory processes. We investigated its diagnostic and prognostic performance in patients with cirrhosis and BI. METHODS Sera of 269 patients were assayed for sTREM-1 by ELISA (172 outpatients and 97 patients with AD of whom 56 had BI). We investigated capacity of sTREM-1 to identify patients with BI and conducted a 90-day follow-up observational study to assess its possible association with short-term mortality. RESULTS sTREM-1 levels were significantly higher in patients with more severe liver disease, BI, and acute-on-chronic liver failure than in patients without these conditions. sTREM-1 had similar accuracy to CRP identifying BI [sTREM-1: AUROC (95%CI) 0.804 (0.711-0.897), p < 0.0001; CRP: 0.791 (0.702-0.881), p < 0.0001)] among AD patients. The combination of these two molecules and the presence of ascites into a composite score significantly increased their discriminative power (AUROC: 0.878, 95%CI: 0.812-0.944, p < 0.0001). High sTREM-1 level (>660 pg/mL) was an independent predictor of 90-day mortality in patients with BI [HR: 2.941, (95%CI: 1.009-8.573), p = 0.048] in our multivariate model. CONCLUSIONS Use of sTREM-1 could increase the recognition of BIs in cirrhosis and help clinicians in mortality risk assessment of these patients.
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Affiliation(s)
- David Tornai
- Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, H-4032 Debrecen, Hungary; Kálmán Laki Doctoral School of Biomedical and Clinical Sciences, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, H-4032 Debrecen, Hungary
| | - Zsuzsanna Vitalis
- Department of Gastroenterology, Institute of Internal Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, H-4032 Debrecen, Hungary
| | - Alexa Jonas
- Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, H-4032 Debrecen, Hungary
| | - Tamas Janka
- Department of Gastroenterology, Institute of Internal Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, H-4032 Debrecen, Hungary
| | - Ildiko Foldi
- Department of Gastroenterology, Institute of Internal Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, H-4032 Debrecen, Hungary
| | - Tamas Tornai
- Department of Gastroenterology, Institute of Internal Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, H-4032 Debrecen, Hungary
| | - Nora Sipeki
- Department of Gastroenterology, Institute of Internal Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, H-4032 Debrecen, Hungary
| | - Aniko Csillag
- Department of Gastroenterology, Institute of Internal Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, H-4032 Debrecen, Hungary
| | - Boglarka Balogh
- Department of Gastroenterology, Institute of Internal Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, H-4032 Debrecen, Hungary
| | - Andrea Sumegi
- HAS-UD Vascular Biology and Myocardial Pathophysiology Research Group, Hungarian Academy of Sciences, 98 Nagyerdei krt, H-4032 Debrecen, Hungary
| | - Roza Foldesi
- Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, H-4032 Debrecen, Hungary
| | - Maria Papp
- Department of Gastroenterology, Institute of Internal Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, H-4032 Debrecen, Hungary
| | - Peter Antal-Szalmas
- Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 98 Nagyerdei krt, H-4032 Debrecen, Hungary.
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Tapadia A, Jain M, Reddy MS, Mahadevan B, Varghese J, Venkataraman J. Serum C-reactive protein and neutrophil-to-lymphocyte ratio as predictors of survival in cirrhotic patients with systemic inflammatory response syndrome and bacterial infection. Indian J Gastroenterol 2021; 40:265-271. [PMID: 33974227 DOI: 10.1007/s12664-020-01134-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Accepted: 11/29/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND Cirrhotic patients are prone to infections due to underlying immune dysfunction in them. We aimed to study the role of inflammatory markers, serum C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR), in predicting infection, blood culture positivity, and short-term (1 month) mortality in hospitalized cirrhotic patients. METHODS This prospective study was done over a period of 14 months (October 2017 to November 2018). Patient data included age, gender, etiology of cirrhosis, reason for admission, and comorbidity. Laboratory tests included blood chemistry and blood cell counts, and blood and urine culture. The specific tests included were CRP and NLR. Survival of patients in the following 1 month was noted. Area under receiver operating characteristic curve (AUROC), sensitivity, specificity, predictive values, diagnostic accuracy were calculated and logistic regression analysis performed. A p-value < 0.05 was considered significant. RESULTS Two hundred and eight patients formed the study cohort. The median age was 51.5 years and male predominance was noted. Alcohol-related liver disease (49%) was the commonest etiology. The infection rate was 62%, culture positivity was 58.5%, and mortality was 30.8%. NLR and CRP were significantly higher in those with documented infection (culture positive or negative) and among nonsurvivors. Optimal cutoffs for NLR and CRP to predict infection were 5.86 and 33.7, respectively. The risk of having an infection was 7.5 times and about 15 times if NLR and CRP were above the cutoffs. The risk of 1-month mortality was 2-3 times higher if patients had NLR and CRP above the cutoffs. The combination of NLR and CRP (≥ 5.86 and ≥ 33.7, respectively) increased specificity and diagnostic accuracy for infection. CONCLUSION NLR and CRP were independently good predictors of infection and 1-month survival among the patients with cirrhosis of liver included in this study.
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Affiliation(s)
- Ashishkumar Tapadia
- Department of Gastroenterology and Hepatology, Gleneagles Global Health City, Chennai 600, 100, India
| | - Mayank Jain
- Department of Gastroenterology and Hepatology, Gleneagles Global Health City, Chennai 600, 100, India.
- Department of Gastroenterology, Arihant Hospital and Research Centre, Indore, 452 009, India.
| | - Mettu Srinivas Reddy
- Institute of Liver Disease and Transplantation, Dr. Rela's Institute of Medical Sciences, Chennai 600 044, India
| | - B Mahadevan
- Department of Gastroenterology and Hepatology, Gleneagles Global Health City, Chennai 600, 100, India
| | - Joy Varghese
- Department of Gastroenterology and Hepatology, Gleneagles Global Health City, Chennai 600, 100, India
| | - Jayanthi Venkataraman
- Department of Gastroenterology and Hepatology, Gleneagles Global Health City, Chennai 600, 100, India
- Department of Hepatology, Sri Ramachandra Medical College, Porur, Chennai 600 116, India
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Popoiag RE, Panaitescu E, Suceveanu AI, Suceveanu AP, Micu SI, Mazilu L, Parepa I, Voinea F, Costea DO, Enache F, Fierbințeanu-Braticevici C. Spontaneous bacterial peritonitis mortality trends of cirrhotic patients in the last decade in Constanta County. Exp Ther Med 2021; 22:732. [PMID: 34007340 PMCID: PMC8120657 DOI: 10.3892/etm.2021.10164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Accepted: 02/02/2021] [Indexed: 11/26/2022] Open
Abstract
Spontaneous bacterial peritonitis (SBP) is a complication of liver cirrhosis with an increased in-hospital mortality rate. For this reason, the aim of the present study was to examine the main predictors of mortality in order to be able to identify high-risk patients in time and to guide the optimal treatment for prognosis improvement. We retrospectively collected demographic, clinical, laboratory and treatment data as well as data regarding length of stay and cost of hospitalization from 72 patients diagnosed with SBP between January 2010 and December 2019 in the Emergency Clinical Hospital St. Apostle Andrew, Constanta, Romania. Patients were divided into two groups: Those who survived and those who died. Logistic regression was used to identify a possible association between these factors and the increased risk of mortality. Univariate analysis revealed that clinical factors (fever, chills, and hepatic encephalopathy), biological factors such as serum and ascites leukocyte value, polymorphonuclear percentage (PMN), erythrocyte sedimentation rate (ESR) value, previous SBP episodes, and the presence of complications such as acute kidney injury (AKI), sepsis, and systemic inflammatory response syndrome (SIRS) were significantly associated with in-hospital mortality in patients with SBP. Multivariate analysis revealed that SIRS (P=0.0010) and fever (P=0.0258) were significantly associated with in-hospital mortality in patients with SBP. Findings of the present study suggest that, SIRS and fever were independent predictive factors of mortality in cirrhotic patients with SBP.
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Affiliation(s)
- Roxana-Emanuela Popoiag
- Department of Internal Medicine 'Ovidius' University, Faculty of Medicine, 900527 Constanta, Romania
| | - Eugenia Panaitescu
- Department of Informatics and Biostatistics, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Andra-Iulia Suceveanu
- Department of Internal Medicine, Emergency Hospital, 'Ovidius' University, Faculty of Medicine, 900527 Constanta, Romania
| | - Adrian-Paul Suceveanu
- Department of Internal Medicine, Emergency Hospital, 'Ovidius' University, Faculty of Medicine, 900527 Constanta, Romania
| | - Sergiu Ioan Micu
- Department of Internal Medicine, Emergency Hospital, 'Ovidius' University, Faculty of Medicine, 900527 Constanta, Romania
| | - Laura Mazilu
- Department of Oncology, Emergency Hospital, 'Ovidius' University, Faculty of Medicine, 900527 Constanta, Romania
| | - Irinel Parepa
- Department of Cardiology, Emergency Hospital, 'Ovidius' University, Faculty of Medicine, 900527 Constanta, Romania
| | - Felix Voinea
- Department of Urology, Emergency Hospital, 'Ovidius' University, Faculty of Medicine, 900527 Constanta, Romania
| | - Daniel Ovidiu Costea
- Department of Surgery, Emergency Hospital, 'Ovidius' University, Faculty of Medicine, 900527 Constanta, Romania
| | - Florin Enache
- Department of Pediatric Surgery, Emergency Hospital, 'Ovidius' University, Faculty of Medicine, 900527 Constanta, Romania
| | - Carmen Fierbințeanu-Braticevici
- Department of Gastroenterology, University Hospital, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania
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Choi HJ, Yun JW, Kim YH, Kwon E, Hyon MK, Kim JY, Che JH, Ho Kim W, Seong SY, Kang BC. Evaluation of acute and subacute toxicity of sodium taurodeoxycholate in rats. Drug Chem Toxicol 2021; 44:268-276. [PMID: 31215257 DOI: 10.1080/01480545.2019.1609493] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2018] [Revised: 01/06/2019] [Accepted: 01/22/2019] [Indexed: 12/21/2022]
Abstract
Taurodeoxycholate (TDCA) inhibits various inflammatory responses suggesting potential clinical application. However, the toxicity of TDCA has not been evaluated in detail in vivo. We investigated the acute toxicity and 4-week repeated-dose toxicity of TDCA following intravenous infusion under Good Laboratory Practice regulations. In the sighting study of acute toxicity, one of two rats (one male and one female) treated with 300 mg/kg TDCA died with hepatotoxicity, suggesting that the approximate 50% lethal dose of TDCA is 300 mg/kg. Edema and discoloration were observed at the injection sites of tails when rats were infused with 150 mg/kg or higher amount of TDCA once. In 4-week repeated-dose toxicity study, no treatment-related mortality or systemic changes in hematology and serum biochemistry, organ weights, gross pathology, or histopathology were observed. However, the tail injection site showed redness, discharge, hardening, and crust formation along with histopathological changes such as ulceration, edema, fibrosis, and thrombosis when rats were infused with 20 mg/kg TDCA. Taken together, TDCA induced no systemic toxicity or macroscopic lesions at the injection site at a dose of 10 mg/kg/day, which is 33 times higher than the median effective dose observed in a mouse sepsis model. These findings suggest that TDCA might have a favorable therapeutic index in clinical applications.
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Affiliation(s)
- Hyung Jun Choi
- Graduate School of Translational Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
| | - Jun-Won Yun
- Department of Biotechnology, The Catholic University of Korea, Bucheon, Republic of Korea
| | - Youn-Hee Kim
- Wide River Institute of Immunology, Department of Microbiology and Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Euna Kwon
- Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
| | - Min-Kyong Hyon
- Graduate School of Translational Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
| | - Ji Young Kim
- Graduate School of Translational Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
| | - Jeong-Hwan Che
- Biomedical Center for Animal Resource and Development, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Woo Ho Kim
- Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Seung-Yong Seong
- Wide River Institute of Immunology, Department of Microbiology and Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Byeong-Cheol Kang
- Graduate School of Translational Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
- Biomedical Center for Animal Resource and Development, Seoul National University College of Medicine, Seoul, Republic of Korea
- Designed Animal and Transplantation Research Institute, Institute of GreenBio Science Technology, Seoul National University, Pyeongchang-gun, Gangwon-do, Republic of Korea
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Zhang J, Wang C, Wang H, Li X, Xu J, Yu K. Loganin alleviates sepsis-induced acute lung injury by regulating macrophage polarization and inhibiting NLRP3 inflammasome activation. Int Immunopharmacol 2021; 95:107529. [PMID: 33744777 DOI: 10.1016/j.intimp.2021.107529] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 02/21/2021] [Accepted: 02/22/2021] [Indexed: 10/21/2022]
Abstract
Sepsis is a systemic inflammatory response syndrome resulted from severe infection. Excessive inflammation response plays an important role in sepsis-induced acute lung injury (ALI). Loganin is an iridoid glycoside isolated from Corni fructus and exerts an anti-inflammatory effect in multiple inflammatory diseases; however, the role of loganin in sepsis-induced ALI remains unknown. In the current study, the cecal ligation and puncture (CLP)-induced murine sepsis model was constructed to investigate the anti-inflammatory property of loganin in sepsis-induced ALI. Lipopolysaccharide (LPS)-treated Raw 264.7 cells and primary murine peritoneal macrophages were established to further explore underlying mechanism of loganin. Results showed that intragastrical administration of loganin significantly increased murine survival, reduced the alveolar structure damage and inflammatory cell infiltration. Loganin suppressed the release of the M1 macrophage-associated pro-inflammatory cytokines and induced the activation of M2-type anti-inflammatory cytokines. Besides, loganin dramatically inhibited NLRP3 inflammasome-mediated caspase-1 activation and subsequent IL-1β secretion. Further in vitro studies confirmed that loganin efficiently inhibited M1 macrophage polarization and NLRP3 inflammasome activation by blocking the extra-cellular signal-regulated kinase (ERK) and nuclear factor-kappa B (NF-κB) pathways. Taken together, the anti-inflammatory effect of loganin in sepsis-induced ALI was associated with the ERK and NF-κB pathway-mediated macrophage polarization and NLRP3 inflammasome activation. Our study offers a favorable mechanistic basis to support the therapeutic potential of loganin in anti-inflammatory diseases, such as sepsis-induced ALI.
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Affiliation(s)
- Jin Zhang
- Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, Heilongjiang 150001, China
| | - Changsong Wang
- Department of Critical Care Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, China
| | - Hongliang Wang
- Department of Critical Care Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, Heilongjiang 150001, China
| | - Xueting Li
- Department of Critical Care Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, China
| | - Jingjing Xu
- Department of Critical Care Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, China
| | - Kaijiang Yu
- Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, Heilongjiang 150001, China.
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Choi HJ, Yun JW, Kim YH, Kwon E, Hyon MK, Kim JY, Che JH, Park JS, Kim HC, Ho Kim W, Seong SY, Kang BC. Nonclinical toxicology studies with sodium taurodeoxycholate: acute and subacute toxicity in dogs. Drug Chem Toxicol 2021; 44:161-169. [PMID: 31215246 DOI: 10.1080/01480545.2019.1566352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2018] [Revised: 12/18/2018] [Accepted: 12/20/2018] [Indexed: 10/26/2022]
Abstract
Sodium taurodeoxycholate (TDCA) has been investigated for various inflammatory disorders such as sepsis. We recently evaluated nonclinical safety profile of TDCA using rats infused intravenously. As a series of preclinical safety investigations, we further conducted toxicity studies with TDCA delivered to dogs via intravenous administration under Good Laboratory Practice regulation in this study. In dose range-finding study (dose escalation study), dogs given with TDCA at a dose of 150 mg/kg showed marked changes in clinical signs, hematology, and serum biochemistry. And biochemical markers of liver damage and local skin lesions were observed following intravenous infusion of 100 mg/kg TDCA, suggesting that 100 mg/kg was chosen as the highest dose of TDCA for 4-week repeated-dose toxicity study using dogs. Despite no treatment-related significant changes in body weight, food consumption, ophthalmoscopy, and urinalysis, skin lesions were observed at the injection site of animals administered with higher than 50 mg/kg of TDCA along with biochemical and histopathological changes associated with liver injury. However, most of off-target effects were found to be reversible since these were recovered after stopping TDCA infusion. These findings indicate that the no-observed-adverse-effect-level (NOAEL) for TDCA in dogs was considered to be 5 mg/kg/d. Taken together, our results provide important toxicological profiles regarding the safe dose of TDCA for drug development or clinical application.
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Affiliation(s)
- Hyung Jun Choi
- Graduate School of Translational Medicine, College of Medicine, Seoul National University, Seoul, Republic of Korea
- Department of Experimental Animal Research, Biomedical Research Institute Seoul National University Hospital, Seoul, Republic of Korea
| | - Jun-Won Yun
- Department of Biotechnology, The Catholic University of Korea, Bucheon, Republic of Korea
| | - Youn-Hee Kim
- Department of Microbiology and Immunology, Department of Biomedical Sciences, Wide River Institute of Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Euna Kwon
- Department of Experimental Animal Research, Biomedical Research Institute Seoul National University Hospital, Seoul, Republic of Korea
| | - Min-Kyong Hyon
- Graduate School of Translational Medicine, College of Medicine, Seoul National University, Seoul, Republic of Korea
- Department of Experimental Animal Research, Biomedical Research Institute Seoul National University Hospital, Seoul, Republic of Korea
| | - Ji Young Kim
- Graduate School of Translational Medicine, College of Medicine, Seoul National University, Seoul, Republic of Korea
- Department of Experimental Animal Research, Biomedical Research Institute Seoul National University Hospital, Seoul, Republic of Korea
| | - Jeong-Hwan Che
- Biomedical Center for Animal Resource and Development, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jin-Sung Park
- Department of Experimental Animal Research, Biomedical Research Institute Seoul National University Hospital, Seoul, Republic of Korea
| | - Hyoung-Chin Kim
- Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Republic of Korea
| | - Woo Ho Kim
- Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Seung-Yong Seong
- Department of Microbiology and Immunology, Department of Biomedical Sciences, Wide River Institute of Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Byeong-Cheol Kang
- Graduate School of Translational Medicine, College of Medicine, Seoul National University, Seoul, Republic of Korea
- Department of Experimental Animal Research, Biomedical Research Institute Seoul National University Hospital, Seoul, Republic of Korea
- Biomedical Center for Animal Resource and Development, Seoul National University College of Medicine, Seoul, Republic of Korea
- Designed Animal and Transplantation Research Institute, Institute of GreenBio Science Technology, Seoul National University, Pyeongchang-gun, Republic of Korea
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Mahmud N, Asrani SK, Kaplan DE, Ogola GO, Taddei TH, Kamath PS, Serper M. The Predictive Role of Model for End-Stage Liver Disease-Lactate and Lactate Clearance for In-Hospital Mortality Among a National Cirrhosis Cohort. Liver Transpl 2021; 27:177-189. [PMID: 37160007 PMCID: PMC7880877 DOI: 10.1002/lt.25913] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 08/28/2020] [Accepted: 09/22/2020] [Indexed: 02/06/2023]
Abstract
The burden of cirrhosis hospitalizations is increasing. The admission Model for End-Stage Liver Disease-lactate (MELD-lactate) was recently demonstrated to be a superior predictor of in-hospital mortality compared with MELD in limited cohorts. We identified specific classes of hospitalizations where MELD-lactate may be especially useful and evaluated the predictive role of lactate clearance. This was a retrospective cohort study of 1036 cirrhosis hospitalizations for gastrointestinal bleeding, infection, or other portal hypertension-related indications in the Veterans Health Administration where MELD-lactate was measured on admission. Performance characteristics for in-hospital mortality were compared between MELD-lactate and MELD/MELD-sodium (MELD-Na), with stratified analyses of MELD categories (≤15, >15 to <25, ≥25) and reason for admission. We also incorporated day 3 lactate levels into modeling and tested for an interaction between day 1 MELD-lactate and day 3 lactate clearance. MELD-lactate had superior discrimination for in-hospital mortality compared with MELD or MELD-Na (area under the curve [AUC] 0.789 versus 0.776 versus 0.760, respectively; P < 0.001) and superior calibration. MELD-lactate had higher discrimination among hospitalizations with MELD ≤15 (AUC 0.763 versus 0.608 for MELD, global P = 0.01) and hospitalizations for infection (AUC 0.791 versus 0.674 for MELD, global P < 0.001). We found a significant interaction between day 1 MELD-lactate and day 3 lactate clearance; heat maps were created as clinical tools to risk-stratify patients based on these clinical data. MELD-lactate had significantly superior performance in predicting in-hospital mortality among patients hospitalized for infection and/or with MELD ≤15 when compared with MELD or MELD-Na. Incorporating day 3 lactate clearance may further improve prognostication.
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Affiliation(s)
- Nadim Mahmud
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA,Leonard David Institute of Health Economics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Sumeet K. Asrani
- Baylor University Medical Center, Baylor Scott and White, Dallas, Texas
| | - David E. Kaplan
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA,Gastroenterology Section, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
| | | | - Tamar H. Taddei
- Division of Digestive Diseases, Yale University School of Medicine, New Haven, CT,VA Connecticut Healthcare System, West Haven, CT
| | | | - Marina Serper
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA,Leonard David Institute of Health Economics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA,Gastroenterology Section, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
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Habib S, Yarlagadda S, Carreon TA, Schader LM, Hsu CH. Fungal Infection in Acutely Decompensated Cirrhosis Patients: Value of Model for End-Stage Liver Disease Score. Gastroenterology Res 2020; 13:199-207. [PMID: 33224366 PMCID: PMC7665857 DOI: 10.14740/gr1255] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Accepted: 10/20/2020] [Indexed: 11/11/2022] Open
Abstract
Background Infection in acute-on-chronic liver failure (ACLF) patients is known to cause higher mortality. The current approach is to culture all patient samples. There are no published data evaluating fungal infections in acutely decompensated patients. In this study, we aim to identify clinical factors predictive of infections within ACLF patients and assess workup compliance within 24 h of hospital admission. Methods We retrospectively analyzed the charts of 457 ACLF patients seen at the University of Arizona between January 1, 2014 and December 31, 2014. We used logistic regression to identify potential risk indicators for bacterial, fungal, and any infections. In order to proceed to a systemic infection workup, the following parameters were assessed: complete blood count, urinalysis, urine culture, bacterial blood culture, chest X-ray, and ascitic fluid analysis in patients with ascites. Additionally, serological markers were also assessed in patient samples. Systemic inflammatory response syndrome (SIRS) was defined as the presence of two or more of the following criteria: temperature > 38 °C or < 36 °C, heart rate > 90 beats/min, respiratory rate > 20 breaths/min, white blood cell count > 12,000 or < 4,000 cells/mm or > 10% bands. Results An established infection was observed in 60.61% of ACLF patients. SIRS criteria predicted infections with concordance statistic (C-statistic) of 0.71 (odds ratio (OR) 6.85, 95% confidence interval (CI): 4.33, 10.85) for any infection, 0.63 (OR 2.88, 95% CI: 1.96, 4.23) for bacterial infection, and 0.53 (OR 1.32, 95% CI: 0.59, 2.96) for fungal infection. After including other significant variables (over 10 additional variables), predictive ability improved, C-statistic 0.83 (95% CI: 0.77, 0.90) for any infection and 0.71 (95% CI: 0.65, 0.77) for bacterial infections. The combination of model for end-stage liver disease (MELD) and hemoglobin (Hb) predicted fungal infections with C-statistic 0.74 (95% CI: 0.63, 0.84). Workup within 24 h of admission was obtained in 12% of patients. Conclusions Fungal infections in ACLF patients results in an increased mortality rate. Elevated MELD and low Hb in combination predict fungal infections. Compliance is very poor to obtain diagnostic workup efficiently, better tools are needed to predict infection upon admission.
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Affiliation(s)
- Shahid Habib
- Liver Institute PLLC, 5295 E. Knight Dr, Tucson, AZ 85712, USA
| | | | | | | | - Chiu-Hsieh Hsu
- Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, The University of Arizona, 1295 N. Martin Ave., Drachman Hall, PO Box 245210, Tucson, AZ 85724, USA
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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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Tan YY, Montagnese S, Mani AR. Organ System Network Disruption Is Associated With Poor Prognosis in Patients With Chronic Liver Failure. Front Physiol 2020; 11:983. [PMID: 32848892 PMCID: PMC7422730 DOI: 10.3389/fphys.2020.00983] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Accepted: 07/20/2020] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND A healthy individual has a high degree of functional connectivity between organ systems, which can be represented graphically in a network map. Disruption of this system connectivity is associated with mortality in life-threatening acute illnesses, demonstrated by a network approach. However, this approach has not been applied to chronic multisystem diseases and may be more reliable than conventional individual organ prognostic scoring methods. Cirrhosis is a chronic disease of the liver with multisystem involvement. Development of an efficient model for prediction of mortality in cirrhosis requires a profound understanding of the pathophysiologic processes that lead to poor prognosis. In the present study, we use a network approach to evaluate the differences in organ system connectivity between survivors and non-survivors in a group of well-characterized patients with cirrhosis. METHODS 201 patients with cirrhosis originally referred to the Clinic five at the University Hospital of Padova, with 13 clinical variables available representing hepatic, metabolic, haematopoietic, immune, neural and renal organ systems were retrospectively enrolled and followed up for 3, 6, and 12 months. Software was designed to compute the correlation network maps of organ system interaction in survivors and non-survivors using analysis indices: A. Bonferroni corrected Pearson's correlation coefficient and B. Mutual Information. Network structure was quantitatively evaluated using the measures of edges, average degree of connectivity and closeness, and qualitatively using clinical significance. Pair-matching was also implemented as a further step after initial general analysis to control for sample size and Model for End-Stage Liver Disease (MELD-Na) score between the groups. RESULTS There was a higher number of significant correlations in survivors, as indicated by both the analysis indices of Bonferroni corrected Pearson's correlation coefficient and the Mutual Information analysis. The number of edges, average degree of connectivity and closeness were significantly higher in survivors compared to non-survivors group. Pair-matching for MELD-Na was also associated with increased connectivity in survivors compared to non-survivors over 3 and 6 months follow up. CONCLUSION This study demonstrates the application of a network approach in evaluating functional connectivity of organ systems in liver cirrhosis, demonstrating a significant degree of network disruption in organ systems in non-survivors. Network analysis of organ systems may provide insight in developing novel prognostic models for organ allocation in patients with cirrhosis.
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Affiliation(s)
- Yen Yi Tan
- Network Physiology Laboratory, UCL Division of Medicine, University College London, London, United Kingdom
| | | | - Ali R. Mani
- Network Physiology Laboratory, UCL Division of Medicine, University College London, London, United Kingdom
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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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Bhandari R, Khaliq K, Ravat V, Kaur P, Patel RS. Chronic Alcoholic Liver Disease and Mortality Risk in Spontaneous Bacterial Peritonitis: Analysis of 6,530 Hospitalizations. Cureus 2020; 12:e8189. [PMID: 32566430 PMCID: PMC7301415 DOI: 10.7759/cureus.8189] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Objective Our study aimed to assess the risk of in-hospital mortality due to chronic alcoholic liver disease (CALD) and other comorbidities in spontaneous bacterial peritonitis (SBP) inpatients. Methods We conducted a cross-sectional study using the Nationwide Inpatient Sample (NIS, 2012 to 2014) from the United States and included 6,530 patients (age 18-50 years) with a primary diagnosis of SBP. Logistic regression was used to evaluate the odds ratio (OR) for in-hospital mortality in SBP by comorbidities. Results The prevalence of CALD in SBP patients is 43.6%, and a higher proportion were males (68.8%) and whites (67%). Middle-aged adults (OR 2.8, 95% CI 1.74-4.45) had higher odds of in-hospital mortality in SBP patients. Race and sex were non-significant predictors for mortality risk. Patients with comorbid coagulopathy (OR 1.9, 95% CI 1.45-2.48) and heart failure (OR 3.9, 95% CI 2.46-6.36) have increased mortality in SBP inpatients. After controlling confounders, CALD was significantly associated with increased in-hospital mortality (OR 1.5, 95% CI 1.12-1.94) in SBP inpatients. Conclusion CALD is an independent factor in increasing the risk of in-hospital mortality in SBP patients by 48%. Alcohol use screening, and alcohol abstinence and supportive therapy need to be implemented at an earlier stage to improve health-related quality of life and reduce in-hospital mortality in SBP patients.
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Affiliation(s)
- Renu Bhandari
- Medicine, Manipal College of Medical Sciences, Kaski, NPL
| | - Khalida Khaliq
- Psychiatry/Medicine, North Tampa Behavioral Health, Tampa, USA
| | | | - Pawandeep Kaur
- Medicine, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, IND
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Abstract
Neutrophil extracellular traps, or NETs, are heterogenous, filamentous structures which consist of extracellular DNA, granular proteins, and histones. NETs are extruded by a neutrophil in response to various stimuli. Although NETs were initially implicated in immune defense, subsequent studies have implicated NETs in a spectrum of disease processes, including autoimmune disease, thrombosis, and cancer. NETs also contribute to the pathogenesis of several common liver diseases, including alcohol-associated liver disease and portal hypertension. Although there is much interest in the therapeutic potential of NET inhibition, future clinical applications must be balanced against potential increased risk of infection.
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Affiliation(s)
- Moira B. Hilscher
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Vijay H. Shah
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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Abstract
Hepatic encephalopathy (HE) is one of the major clinical decompensations of cirrhosis, with a high impact on health care resource utilization and cost. For an effective and comprehensive management of HE, the clinicians need to understand the pathophysiologic mechanisms of HE. This review describes the multiorgan processes involved in HE and how several HE precipitants and treatment strategies act on ammonia production, excretion, and neurotoxicity, including the impact of diabetes and use of cannabinoids. The authors also discuss the current and future role of gut microbiome, systemic/central inflammation, and various neurotransmitters for the pathogenesis and treatment of HE.
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Affiliation(s)
- Ariel Jaffe
- Section of Digestive Diseases, Yale Liver Center, Yale University School of Medicine, 333 Cedar Street, LMP 1080, New Haven, CT 06520-8019, USA
| | - Joseph K Lim
- Section of Digestive Diseases, Yale Liver Center, Yale University School of Medicine, 333 Cedar Street, LMP 1080, New Haven, CT 06520-8019, USA; VA Connecticut Healthcare System, West Haven, Connecticut, USA
| | - Sofia Simona Jakab
- Section of Digestive Diseases, Yale Liver Center, Yale University School of Medicine, 333 Cedar Street, LMP 1080, New Haven, CT 06520-8019, USA; VA Connecticut Healthcare System, West Haven, Connecticut, USA.
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Ueno M, Kayahara T, Sunami T, Takayama H, Takabatake H, Morimoto Y, Yamamoto H, Mizuno M. Universal antibiotic prophylaxis may no longer be necessary for patients with acute variceal bleeding: A retrospective observational study. Medicine (Baltimore) 2020; 99:e19981. [PMID: 32443300 PMCID: PMC7253534 DOI: 10.1097/md.0000000000019981] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
A few decades ago, antibiotic prophylaxis for patients with acute variceal bleeding was reported beneficial. However, endoscopic and systemic therapy for variceal bleeding has dramatically improved since then, so the necessity of prophylactic antibiotics can be questioned. In this study, we reevaluated the efficacy of antibiotic prophylaxis in acute variceal bleeding, using the most recent data in our hospital.We retrospectively analyzed the medical records of 150 patients with acute variceal bleeding who were admitted to Kurashiki Central Hospital between January 2012 and December 2016. We compared the rates of bacterial infection, in-hospital mortality, 5-day rebleeding rate, and 30-day emergency readmission between patients treated or not treated with antibiotic prophylaxis.Forty-six patients (30.7%) received antibiotic prophylaxis; 104 (69.3%) did not. The rates of the outcomes in patients with antibiotic prophylaxis were 6.5% (bacterial infection), 4.3% (in-hospital mortality), 2.2% (5-day rebleeding), and 10.9% (30-day emergency readmission) and were not significantly different form the corresponding figures in those without antibiotic prophylaxis (1.9%, 7.7%, 1.9%, and 10.6%, respectively). Moreover, these rates in our patients, even without antibiotic prophylaxis, were much lower than rates reported in past years, perhaps because of improvements in care of patients with variceal hemorrhage.Antibiotic prophylaxis was not associated with significantly better outcomes of bacterial infection, mortality, rebleeding or readmission rate in patients with acute variceal bleeding. Universal antibiotic prophylaxis for patients with acute variceal bleeding should be reconsidered.
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Diagnostic Value of Presepsin for Bacterial Infection in Cirrhosis: A Pilot Study. Transplant Proc 2020; 52:1593-1600. [PMID: 32305204 DOI: 10.1016/j.transproceed.2020.02.042] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Revised: 01/28/2020] [Accepted: 02/05/2020] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Presepsin (or sCD14) has been identified as a protein whose levels increase specifically in the blood of patients with bacterial infections. In this study, we evaluated the clinical performance of sCD14 and its usefulness in the early diagnosis of bacterial infection in decompensated cirrhotic patients. MATERIALS Seventy patients were enrolled in this study. The mean age of patients was 49.5 years, and 21 were women and 49 men. The heparinized whole blood for the PATHFAST test was used in the evaluation of bacterial infection (T0). The test was repeated after 48 hours (T1); at 96 hours (T2); at 144 hours (T3); then at 15 days (T4) to monitor the clinical responses to therapeutic interventions. RESULTS Forty-nine patients tested positive for sCD14. The mean sCD14 level was 1854 ± 1744 pg/mL. Microbiological findings confirmed the presence of bacterial infections within 84 ± 4.8 h from enrollment in all 49 positive patients. Thirty-eight patients were considered responders to empirical antibiotic therapy with a decrease of presepsin at the different time points, while an increased level of sCD14 was highlighted in 11 patients. When the test was performed, 45% of the patients showed no signs or symptoms of bacterial infection. At 30 days of follow-up 43 patients survived, and 6 patients died from septic shock. CONCLUSIONS The PATHFAST test highlighted the presence of infection in a very short time (15 minutes), and the presepsin could be considered an early biomarker in patients with cirrhosis. A greater number of patients are necessary to confirm these data.
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Liu H, Zhu P, Nie C, Ye Q, Gao Y, Liu H, Pang G, Han T. The value of ascitic neutrophil gelatinase-associated lipocalin in decompensated liver cirrhosis with spontaneous bacterial peritonitis. J Clin Lab Anal 2020; 34:e23247. [PMID: 32100329 PMCID: PMC7307354 DOI: 10.1002/jcla.23247] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Revised: 01/08/2020] [Accepted: 01/29/2020] [Indexed: 12/13/2022] Open
Abstract
Background Spontaneous bacterial peritonitis (SBP) is one of the most critical complications of decompensated liver cirrhosis. This study aimed to assess whether ascitic neutrophil gelatinase‐associated lipocalin (NGAL), a reliable inflammation biomarker, can be used to detect SBP in decompensated cirrhosis patients and to predict mortality from decompensated cirrhosis‐related SBP. Methods This study included 204 hospitalized patients with ascites of decompensated liver cirrhosis and follow‐up of 28 days. We measured ascitic NGAL levels by the latex‐enhanced immunoturbidimetric method. Simultaneously, we observed the patterns of ascitic NGAL levels in the SBP group after 7 days of anti‐infection treatment with third‐generation cephalosporins. Results The ascitic NGAL levels significantly increased in the SBP group compared with that in the non‐SBP group, 111(83.9, 178) ng/mL vs 48(35.4, 63) ng/mL, P < .001. Likewise, the ascitic NGAL levels of SBP were higher than non‐SBP with or without renal dysfunction. There was a positive relationship between ascitic NGAL and ascitic polymorphonuclear (PMN) leukocyte and a negative relationship between ascitic NGAL and ascitic albumin in the SBP group. An ascitic NGAL cutoff of 108.95 ng/mL was used for predicting a poor prognosis for SBP patients. Ascitic NGAL and the model for end‐stage liver disease score were independent risk factors in decompensated liver cirrhosis patients with SBP through multivariate Cox regression. A dynamic trend of ascitic NGAL in SBP patients was consistent with the clinical prognosis. Conclusion Ascitic NGAL may not only be a biomarker for monitoring SBP but also a predictor for more severe outcomes in decompensated cirrhosis‐related SBP.
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Affiliation(s)
- Hua Liu
- Department of Hepatology, The Third Central Clinical College of Tianjin Medical University, Tianjin, China.,Department of Hepatology, The Third Central Hospital of Tianjin, Tianjin, China.,Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China.,Tianjin Institute of Hepatobiliary Disease, Tianjin, China
| | - Ping Zhu
- Department of Hepatology, The Third Central Clinical College of Tianjin Medical University, Tianjin, China.,Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China.,Tianjin Institute of Hepatobiliary Disease, Tianjin, China.,Artificial Cell Engineering Technology Research Center, Tianjin, China
| | - Caiyun Nie
- Department of Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.,Department of Oncology, Henan Cancer Hospital, Zhengzhou, China
| | - Qing Ye
- Department of Hepatology, The Third Central Hospital of Tianjin, Tianjin, China.,Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China.,Tianjin Institute of Hepatobiliary Disease, Tianjin, China.,Artificial Cell Engineering Technology Research Center, Tianjin, China
| | - Yanying Gao
- Department of Hepatology, The Third Central Hospital of Tianjin, Tianjin, China.,Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China.,Tianjin Institute of Hepatobiliary Disease, Tianjin, China.,Artificial Cell Engineering Technology Research Center, Tianjin, China
| | - Huaiping Liu
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China.,Tianjin Institute of Hepatobiliary Disease, Tianjin, China.,Artificial Cell Engineering Technology Research Center, Tianjin, China.,Department of Clinical Laboratory, The Third Central Hospital of Tianjin, Tianjin, China
| | - Guoju Pang
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China.,Tianjin Institute of Hepatobiliary Disease, Tianjin, China.,Artificial Cell Engineering Technology Research Center, Tianjin, China.,Department of Clinical Laboratory, The Third Central Hospital of Tianjin, Tianjin, China
| | - Tao Han
- Department of Hepatology, The Third Central Clinical College of Tianjin Medical University, Tianjin, China.,Department of Hepatology, The Third Central Hospital of Tianjin, Tianjin, China.,Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China.,Tianjin Institute of Hepatobiliary Disease, Tianjin, China
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Cao ZJ, Liu YH, Zhu CW, Yin S, Wang WJ, Tang WL, Zhao GD, Xu YM, Chen L, Zhou TH, Cai MH, Wang H, Cai W, Bao SS, Li H, Xie Q. Bacterial infection triggers and complicates acute-on-chronic liver failure in patients with hepatitis B virus-decompensated cirrhosis: A retrospective cohort study. World J Gastroenterol 2020; 26:645-656. [PMID: 32103873 PMCID: PMC7029352 DOI: 10.3748/wjg.v26.i6.645] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Revised: 01/08/2020] [Accepted: 01/15/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Reports on bacterial infection (BI) in decompensated cirrhosis (DC) is mainly from alcoholic cirrhosis. The role of BI as a trigger or complication of acute-on-chronic liver failure (ACLF) in patients with hepatitis B virus decompensated cirrhosis (HBV-DC) remains to be investigated. AIM To investigate the impact of BI on the outcomes of the patients with HBV-DC admitted into the hospital with or without ACLF. METHODS This retrospective study included patients with HBV-DC admitted to two tertiary centers in China. In-hospital overall survival, 90-d transplant-free survival, 5-year post-discharge survival, and cumulative incidence of ACLF were evaluated. Risk factors for death were analyzed considering liver transplantation as a competing event. RESULTS A total of 1281 hospitalized HBV-DC patients were included; 284 had ACLF at admission. The overall prevalence of BI was 28.1%. The patients with BI had a significantly lower in-hospital survival and transplant-free 90-d survival than those without, in both the patients admitted with and without ACLF. The presence of BI significantly increased the risk of developing ACLF [sub-distribution hazard ratio (sHR) = 2.52, 95%CI: 1.75-3.61, P < 0.001] in the patients without ACLF. In the patients discharged alive, those who had an episode of BI had a significantly lower 5-year transplant-free survival. BI was an independent risk factor for death in the patients admitted without ACLF (sHR = 3.28, 95%CI: 1.93-5.57), while in ACLF admissions, the presence of pneumonia, but not other type of BI, independently increased the risk of death (sHR = 1.87, 95%CI: 1.24-2.82). CONCLUSION BI triggers ACLF in patients with HBV-DC and significantly impairs short-term survival. HBV-DC patients should be monitored carefully for the development of BI, especially pneumonia, to avoid an adverse outcome.
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Affiliation(s)
- Zhu-Jun Cao
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Yu-Han Liu
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Chuan-Wu Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China
| | - Shan Yin
- Department of Gastroenterology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
| | - Wei-Jing Wang
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Department of Infectious Diseases, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai 201801, China
| | - Wei-Liang Tang
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Gang-De Zhao
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Department of Infectious Diseases, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai 201801, China
| | - Yu-Min Xu
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Lu Chen
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Tian-Hui Zhou
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Ming-Hao Cai
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Hui Wang
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Wei Cai
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Shi-San Bao
- Discipline of Pathology, School of Medical Sciences and Bosch Institute, University of Sydney, Sydney, NSW 2006, Australia
| | - Hai Li
- Department of Gastroenterology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Department of Infectious Diseases, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai 201801, China
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Hou JL, Zhao W, Lee C, Hann HW, Peng CY, Tanwandee T, Morozov V, Klinker H, Sollano JD, Streinu-Cercel A, Cheinquer H, Xie Q, Wang YM, Wei L, Jia JD, Gong G, Han KH, Cao W, Cheng M, Tang X, Tan D, Ren H, Duan Z, Tang H, Gao Z, Chen S, Lin S, Sheng J, Chen C, Shang J, Han T, Ji Y, Niu J, Sun J, Chen Y, Cooney EL, Lim SG. Outcomes of Long-term Treatment of Chronic HBV Infection With Entecavir or Other Agents From a Randomized Trial in 24 Countries. Clin Gastroenterol Hepatol 2020; 18:457-467.e21. [PMID: 31306800 DOI: 10.1016/j.cgh.2019.07.010] [Citation(s) in RCA: 69] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Revised: 06/17/2019] [Accepted: 07/03/2019] [Indexed: 02/05/2023]
Abstract
BACKGROUND & AIMS Treatment of chronic hepatitis B virus (HBV) infection with entecavir suppresses virus replication and reduces disease progression, but could require life-long therapy. To investigate clinical outcome events and safety associated with long-term treatment with entecavir, we followed up patients treated with entecavir or another standard-of-care HBV nucleos(t)ide analogue for up to 10 years. We assessed long-term outcomes and relationships with virologic response. METHODS Patients with chronic HBV infection at 299 centers in Asia, Europe, and North and South America were assigned randomly to groups that received entecavir (n = 6216) or an investigator-selected nonentecavir HBV nucleos(t)ide analogue (n = 6162). Study participants were followed up for up to 10 years in hospital-based or community clinics. Key end points were time to adjudicated clinical outcome events and serious adverse events. In a substudy, we examined relationships between these events and virologic response. RESULTS There were no significant differences between groups in time to event assessments for primary end points including malignant neoplasms, liver-related HBV disease progression, and death. There were no differences between groups in the secondary end points of nonhepatocellular carcinoma malignant neoplasms and hepatocellular carcinoma. In a substudy of 5305 patients in China, virologic response, regardless of treatment group, was associated with a reduced risk of liver-related HBV disease progression (hazard ratio, 0.09; 95% CI, 0.038-0.221) and hepatocellular carcinoma (hazard ratio, 0.03; 95% CI, 0.009-0.113). Twelve patients given entecavir (0.2%) and 50 patients given nonentecavir drugs (0.8%) reported treatment-related serious adverse events. CONCLUSIONS In a randomized controlled trial of patients with chronic HBV infection, we associated entecavir therapy with a low rate of adverse events over 10 years of follow-up evaluation. Patients receiving entecavir vs another nucleos(t)ide analogue had comparable rates of liver- and non-liver-related clinical outcome events. Participants in a China cohort who maintained a virologic response, regardless of treatment group, had a reduced risk of HBV-related outcome events including hepatocellular carcinoma. ClinicalTrials.gov identifier no: NCT00388674.
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Affiliation(s)
- Jin-Lin Hou
- Department of Infectious Diseases, Institute of Hepatology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
| | - Wei Zhao
- Department of Infectious Diseases, 2nd Hospital Nanjing, Nanjing, China
| | | | - Hie-Won Hann
- Division of Gastroenterology and Hepatology, Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
| | - Cheng-Yuan Peng
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Tawesak Tanwandee
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand
| | | | - Hartwig Klinker
- Department of Medicine II, Division of Hepatology, University of Würzburg Medical Center, Würzberg, Germany
| | - Jose D Sollano
- Department of Medicine, Cardinal Santos Medical Center, Manila, Philippines
| | - Adrian Streinu-Cercel
- Department of Infectious Diseases I, Carol Davila University of Medicine and Pharmacy, National Institute for Infectious Diseases, "Prof. Dr. Matei Bals," Bucharest, Romania
| | - Hugo Cheinquer
- Gastroenterology and Hepatology Division, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil
| | - Qing Xie
- Department of Infectious Diseases, Shanghai Rui Jin Hospital, Shanghai, China
| | - Yu-Ming Wang
- Institute for Infectious Diseases, Southwest Hospital, Chongqing, China
| | - Lai Wei
- Hepatology Department, Peking University People's Hospital, Beijing, China
| | - Ji-Dong Jia
- National Clinical Research Center for Digestive Disease, Beijing Friendship Hospital, Capitol Medical University, Beijing, China
| | - Guozhong Gong
- Department of Infectious Disease, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Kwang-Hyub Han
- Department of Internal Medicine, Institute of Gastroenterology and Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Wukui Cao
- Department of Infectious Diseases, Tianjin Second People's Hospital, Tianjin, China
| | - Mingliang Cheng
- Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College, Guiyang, China
| | - Xiaoping Tang
- Department of Infectious Diseases, Guangzhou No. 8 People's Hospital, Guangzhou, China
| | - Deming Tan
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, China
| | - Hong Ren
- Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhongping Duan
- Beijing Institute of Hepatology, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Zhiliang Gao
- Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Shijun Chen
- Hepatology Department, Jinan Infectious Disease Hospital, Jinan, China
| | - Shumei Lin
- Department of Infectious Diseases, The First Affiliated Hospital of Xi'An Jiaotong University, Xi'An, China
| | - Jifang Sheng
- Department of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Chengwei Chen
- Hepatology Department, 85th Hospital of People's Liberation Army, Shanghai, China
| | - Jia Shang
- Department of Infectious Diseases, Henan Provincial People's hospital, Zhengzhou, China
| | - Tao Han
- Department of Hepatology and Gastroenterology, Tianjin Third Central Hospital, Tianjin, China
| | - Yanyan Ji
- Hepatology Department, Shanghai Jing'an District Central Hospital, Shanghai, China
| | - Junqi Niu
- Hepatobiliary Medical Ward, The First Hospital of Jilin University, Changchun, China
| | - Jian Sun
- Department of Infectious Diseases, Institute of Hepatology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yongpeng Chen
- Department of Infectious Diseases, Institute of Hepatology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | | | - Seng-Gee Lim
- Division of Gastroenterology and Hepatology, National University Health System, National University of Singapore, Singapore
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