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Organ System Network Disruption Is Associated With Poor Prognosis in Patients With Chronic Liver Failure.

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.

SUBMITTER: Tan YY

PROVIDER: S-EPMC7422730 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Organ System Network Disruption Is Associated With Poor Prognosis in Patients With Chronic Liver Failure.

Tan Yen Yi YY Montagnese Sara S Mani Ali R AR

Frontiers in physiology 20200805

<h4>Background</h4>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 o ...[more]

PMID: 32848892

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Project description:Acute liver failure (ALF) is a syndrome characterized by an intense systemic inflammatory response (SIRS) and multi-organ system failure (MOSF). Platelet-derived microparticles increase in proportion to the severity of the SIRS and MOSF, and are associated with poor outcome. We investigated whether patients with ALF develop thrombocytopenia in proportion to the SIRS, MOSF, and poor outcome.In a retrospective study, we collected data on the post-admission platelet counts of 1598 patients included in the ALF Study Group Registry from 1998 through October 2012. We investigated correlations between platelet counts and clinical features of ALF, laboratory test results, and outcomes. Of the patients studied, 752 (47%) survived without liver transplantation, 390 (24%) received liver transplants, and 517 (32%) died.In patients with SIRS, platelet counts decreased 2 to 7 days after admission, compared with patients without SIRS (P ? .001). Patients with abnormal levels of creatinine, phosphate, lactate, or bicarbonate had significantly lower platelet counts than patients with normal levels of these laboratory values (all P ? .001). The decrease in platelets during days 1 to 7 after admission was proportional to the grade of hepatic encephalopathy and requirement for vasopressor and renal replacement therapy. Although platelet numbers decreased after admission in the overall population, platelets were significantly lower 2 to 7 days after admission in patients with outcomes of death or liver transplantation than in patients who made spontaneous recoveries and survived. In contrast, international normalized ratios over time were not associated with SIRS, laboratory test results associated with poor outcomes, grade of hepatic encephalopathy, or requirement for renal replacement therapy.The development of thrombocytopenia in patients with ALF is associated with the development of MOSF and poor outcome. We speculate that SIRS-induced activation of platelets, yielding microparticles, results in clearance of platelet remnants and subsequent thrombocytopenia.

Project description:Background & aimsStudies regarding acute-on-chronic liver failure (ACLF) among liver transplant (LT) candidates from the United Network for Organ Sharing (UNOS) database are being used to inform LT policy changes worldwide. We assessed the validity of identifying ACLF in UNOS.MethodsWe performed stratified random sampling among 3 US LT centers between 2013-2019 to obtain a representative patient sample across ACLF grades. We compared the concordance of ACLF classification by UNOS vs. blinded manual chart review, according to EASL-CLIF.ResultsAmong 481 sampled LT registrants, 250 (52%) had no ACLF, 75 (16%) had ACLF grade 1, 79 (16%) had ACLF grade 2, and 77 (16%) had ACLF grade 3 per UNOS categorization. Concordance of ACLF grade by UNOS vs. chart review was: 72%, 64%, 56%, and 64% for no ACLF, grade 1, grade 2, and grade 3, respectively, with an overall Cohen's kappa coefficient of 0.48 (95% CI 0.42-0.54). Absence of acute decompensation was the most common reason for overestimation, and discordant brain and respiratory failure categorization were the most common reasons for underestimation of ACLF by UNOS.ConclusionsIn this retrospective multi-center study, ACLF categorization by UNOS showed weak agreement with manual chart review. These findings are informative for ongoing allocation policy discussions, highlight the importance of prospective studies regarding ACLF in LT, and should encourage UNOS reform.Lay summaryAcute-on-chronic-liver-failure (ACLF) is a specific and common form of liver failure associated with high death rates. Studies have been published using the United States transplant registry (UNOS) to identify and describe outcomes of transplant candidates and recipients with ACLF, and these data are driving policy changes for transplant allocation around the world, but nobody has shown whether these data are reliable. We found that UNOS was not categorizing ACLF in concordance or accurately when compared to chart review, which shows the need for UNOS reform and non-UNOS studies to appropriately inform policies regarding the transplantation of patients with ACLF.

Project description:InductionLiver transplantation (LT) is the only final therapy for patients with acute liver failure (ALF) that cannot be controlled by conservative treatment. Acute pancreatitis (AP) is a recognized complication of ALF. The pathogenesis of AP in ALF patients has not yet been elucidated. The appearance of AP complicates the patients condition and causes a significantly increased risk of mortality.Patient concernsWe report 2 fatal cases who were both admitted with yellowing of skin and sclera with general weakness lasting for 2 weeks.DiagnosisAfter admission, the laboratory examination of case 1 showed liver dysfunction with serum levels of total bilirubin (TB) 270 μmol/l, alanine aminotransferase (ALT) 106 U/l. Abdominal computed tomography (CT) showed pelvic and peritoneal cavity fluids, occupation of left lateral lobe of liver and unclear margin of pancreas. The clinical laboratory findings of case 2 revealed TB 351.1 μmol/l, ALT 252 U/l, blood lactic acid 18 mmol/l, ammonia 209 μmol/l. And abdominal CT showed pancreatic exudation. They were both diagnosed with acute liver failure, hepatic encephalopathy and AP which was confirmed during the operation.InterventionsThey were both received a routine orthotopic LT.OutcomesAfter the surgery, their liver functions recovered well, and they received conventional conservative treatment for pancreatitis. However, the treatment was not adequately effective, and the infection was too serious and both died of multiple organ failure despite emergency rescue efforts on day 21 and day 19 after LT.ConclusionAP is a serious complication that can contribute to prohibitive morbidity and mortality in LT patients. For this reason, the vulnerable state of the pancreas and the scoring system must be defined to help clinicians decide whether a patient is suitable for liver transplantation, and the clinical experience in the treatment of pancreatitis after LT needs to be summarized as an optimal treatment guideline to facilitate better treatment.

Dataset Information

Organ System Network Disruption Is Associated With Poor Prognosis in Patients With Chronic Liver Failure.

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Organ System Network Disruption Is Associated With Poor Prognosis in Patients With Chronic Liver Failure.

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