Thesis (Ph. D.)--University of Queensland, 2002. / Includes bibliographical references.

Εισαγωγή: Η κίρρωση ήπατος αποτελεί μία σοβαρή και γενικά μη αναστρέψιμη κατάσταση, η οποία συχνά επιπλέκεται από λοιμώξεις, με προεξάρχουσα την αυτόματη βακτηριακή περιτονίτιδα. Η εκδήλωση βακτηριακής λοίμωξης στους κιρρωτικούς συνοδεύεται από υψηλή θνητότητα, ενώ η ύπαρξη της κιρρωτικής νόσου θεωρείται κακός προγνωστικός παράγοντας σε σοβαρές λοιμώξεις. Σκοπός της παρούσας μελέτης ήταν η διερεύνηση της επίδρασης της κίρρωσης στην επίπτωση λοιμώξεων και την Τ κυτταρική απάντηση ασθενών με κίρρωση ήπατος. Ασθενείς και Μέθοδο: Η μελέτη περιέλαβε 74 ασθενείς με κίρρωση ήπατος, οποιασδήποτε αιτιολογίας, που εισήχθησαν στην παθολογική κλινική του Περιφερικού Γενικού Νοσοκομείου Πατρών από Μάιο 2006 έως Ιούνιο 2007. Τριάνταεννέα (39) από τους ασθενείς (52,7%, ομάδα 1) εισήχθησαν για διάφορους λόγους εκτός από λοίμωξη, 21 ασθενείς (28,4%, ομάδα 2) παρουσίασαν σύνδρομο σήψης και 14 (18,9%, ομάδα 3) επεισόδιο κιρσορραγίας. Στο περιφερικό αίμα όλων των ασθενών προσδιορίστηκαν οι Τ λεμφοκυτταρικοί πληθυσμοί, δηλαδή CD3, CD56, CD4, CD8, CD5 και CD20 καθώς και οι CD14 και CD64 υποπληθυσμοί ουδετερόφιλων και μονοκυττάρων, με την τεχνική της κυτταρομετρίας ροής. Στους ασθενείς της ομάδας 1, ο προσδιορισμός των κυτταρικών πληθυσμών έγινε μόνο κατά την πρώτη ημέρα νοσηλείας, ενώ στους ασθενείς της ομάδας 2 και 3, μετρήσεις λήφθηκαν και κατά την τρίτη ημέρα νοσηλείας καθώς και την ημέρα εξόδου. Αποτελέσματα: Παρατηρήθηκε τάση ελάττωσης των κυτταρικών πληθυσμών σε σηπτικούς κιρρωτικούς ασθενείς, χωρίς όμως στατιστική σημασία. Αντίθετα, σημειώθηκε στατιστικά σημαντική μείωση των Τ λεμφοκυτταρικών πληθυσμών σε ασθενείς με κιρσορραγία [CD3: 693 ±85 vs 357 ± 71 (p<0.05), CD4: 425 ± 46 vs 236 ± 48 (p<0.05), CD8: 233 ± 27 vs 128 ± 32 (p<0.05), CD56: 188 ± 28 vs 120 ± 39, σε ασθενείς με κίρρωση vs κιρσορραγία αντίστοιχα]. . Συμπερασματικά, φαίνεται ότι η ανοσιακή απάντηση σε σηπτικούς ασθενείς με κίρρωση δεν επηρεάζεται σημαντικά, αντιθέτως επηρεάζεται σημαντικά σε ασθενείς με κιρσορραγία. Φαίνεται ότι οι ασθενείς με αιμορραγία κιρσών παρουσιάζουν καταστολή της Τ-κυτταρικής ανοσιακής απάντησης και πρέπει να αντιμετωπίζονται με την κατάλληλη αντιμικροβιακή αγωγή. / Introduction: Liver cirrhosis is a serious and generally non reversible condition, often complicated by infections, most commonly spontaneous bacterial peritonitis. Bacterial infections in cirrhotics are accompanied by a high mortality rate, while the presence of cirrhosis alone is considered to be a bad prognostic marker in serious infections. The aim of the present study was the investigation of the effect of liver cirrhosis on the onset of infections and the association with T-cell immune response in patients with cirrhosis of the liver. Patients and methods: The study included 74 patients with liver cirrhosis, who were admitted to the hospital from May 2006 until June 2007. Thirtynine patients (52,7%, group 1) were admitted for reasons other than infection, 21 (28,4%, group 2) presented septic syndrome and 14 (18,9%, group 3) with variceal bleeding. Determination of T-cell subsets (CD3, CD4, CD5, CD8, CD56, CD20) as well as CD14 and CD64 subsets of monocytes and neutophils took place, using flow cytometry. Measurements for group 1 were taken only on the first day of admission, while for patients of group 2 and 3 measurements were repeated on the third and exit day. Results: Decrease of cell subsets was observed in septic cirrhotics with no statistical significance. On the contrary, significant decrease was observed in T-cel subsets in cirrhotic patients with variceal bleeding [CD3: 693 ±85 vs 357 ± 71 (p<0.05), CD4: 425 ± 46 vs 236 ± 48 (p<0.05), CD8: 233 ± 27 vs 128 ± 32 (p<0.05), CD56: 188 ± 28 vs 120 ± 39, cirrhotics vs patients with variceal bleeding respectively]. Conclusions: It seems that the immune systen in septic patients with liver cirrhosis is not affected during infections, while it appears to be compromised in patients with variceal bleeding. The demonstrated depression of T-cell immune response in cirrhotics presented with variceal bleeding reflects immunosupression of the immune system, and these patients should be confronted with the appropriate antibiotic regime.

Thesis (M.D.)—Boston University

INTRODUCTION: Cirrhosis is a significant cause of mortality and morbidity worldwide. Recent studies suggested that cirrhosis is associated with an increased risk of venous thromboembolism (VTE), which disproves the old belief that chronic liver disease coagulopathy is considered protective against VTE. We conducted a retrospective study which is to our knowledge the first of its kind to assess clinical characteristics and outcomes of decompensated cirrhosis (DC) patients admitted with acute pulmonary embolism (APE). METHODOLOGY: We used the National Inpatient Sample database for the years 2016-2019. All adults admitted to the hospitals with a primary diagnosis of APE were included. Patients less than 18 years old, missing race, gender, or age were excluded. Patients were divided into two groups, either having DC or not. A multivariate logistic regression model was built by using only variables associated with the outcome of interest on univariable regression analysis at P < 0.05. RESULTS: 142 million discharges were included in the NIS database between the years 2016 and 2019, of which 1,294,039 met the study inclusion criteria, 6,200 patients (0.5%) had DC. For adult patients admitted to the hospitals with APE, odds of inpatient all-cause mortality were higher in the DC group than in patients without DC; OR of 1.996 (95% CI, 1.691-2.356, P-value < 0.000). Also, vasopressor use, mechanical ventilation, and cardiac arrest were more likely to occur in the DC group, OR of 1.506 (95% CI, 1.254-1.809, P-value < 0.000), OR of 1.479 (95% CI, 1.026-2.132, P-value 0.036), OR of 1.362 (95% CI, 1.050-1.767, P-value 0.020), respectively. In addition, DC patients tend to have higher total hospital charges and longer hospital length of stay, coefficient of 14521 (95% CI, 6752-22289, P-value < 0.000), and a coefficient of 1.399 (95% CI, 0.848-1.950, P-value < 0.000), respectively. CONCLUSION: This study demonstrates that DC is a powerful predictor of worse hospital outcomes in patients admitted with APE. An imbalance between clotting factors and natural anticoagulants produced by the liver is believed to be the primary etiology of thrombosis in patients with DC. The burden of APE can be much more catastrophic in cirrhotic than in non-cirrhotic patients; therefore, those patients require closer monitoring and more aggressive treatment.

published_or_final_version / Physiology / Master / Master of Philosophy

No description available.

No description available.

Introduction: Hepatorenal syndrome (HRS) is a common complication of advanced cirrhosis with a high mortality rate and limited treatment options. Central to its pathogenesis is severe, but potentially reversible, renal vasoconstriction leading to functional renal failure. Current pharmacological treatment using splanchnic vasoconstrictors is suboptimal and prognosis without liver transplantation is dismal. The peptide hormone relaxin (RLN) mediates haemodynamic adaptations to pregnancy including increased renal blood flow (RBF) and glomerular filtration rate (GFR). I hypothesised that exogenous RLN could be used therapeutically to improve RBF and renal function in the context of experimental cirrhosis and HRS. Methods: To address this I generated pathologically distinct rat models of liver cirrhosis with features of human HRS including renal vasoconstriction and renal failure. Compensated cirrhosis was induced in male rats by 16 weeks of i.p. carbon tetrachloride (CCl4) and decompensated cirrhosis by bile duct ligation (BDL). I studied the effects of acute i.v. or sustained (72 hr) s.c. infusion of RLN compared with vehicle on systemic haemodynamics, RBF, GFR and kidney histology. I used blood oxygen dependent-magnetic resonance imaging (BOLD-MRI) to detect changes in kidney parenchymal oxygenation and Doppler ultrasound to monitor changes in RBF (velocity time integral, VTI) and renal arterial resistance (resistive index, RI). Hepatic and renal expression of the relaxin receptor RXFP1 was determined by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Vascular functional responses in isolated renal arteries were assessed by wire myography. Relaxin mediated changes in key vaso-regulatory signalling pathways in the kidney and renal vessels were analysed by qPCR, IHC and ELISA. Results: I showed using in vitro myography that the pathophysiological mechanism that underlies renal vasoconstriction in experimental cirrhosis models is an impairment of endothelium-dependent vasodilatation. Selective targeting of renal vasoconstriction using relaxin improved renal blood flow, tissue oxygenation, and normalized glomerular filtration rate in both compensated and decompensated rat cirrhosis. Furthermore, relaxin treatment restored endothelium-dependent vasodilation in isolated renal vessels from CCl4 cirrhotic rats. Relaxin-induced effects on renal blood flow and glomerular filtration rate were mediated though activation of the AKT/eNOS/nitric oxide signalling pathway in kidney, though systemic nitric oxide levels were unaffected. Crucially for human translation, relaxin did not reduce mean arterial blood pressure even in advanced cirrhosis. Conclusion: My findings identify relaxin as the first potential targeted treatment reversing the vascular dysfunction which causes HRS and directly improving renal function in HRS. Clinical translation in carefully selected populations is warranted.

Made available in DSpace on 2014-06-11T19:31:01Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-05-27Bitstream added on 2014-06-13T20:01:22Z : No. of bitstreams: 1 inoue_rm_dr_botfm.pdf: 589090 bytes, checksum: ea16d419cf739717f9304922ab4c9de5 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A cirrose hepática é definida como um processo difuso de fibrose intersticial associada à formação de nódulos regenerativos e à modificação na fígado, a repercussão da cirrose hepática é sistêmica. Assim, na fase avançada da doença são descritas alterações cerebrais como a encefalopatia hepática, renais ..• como a síndrome hepato-renal, pulmonares como a síndrome porto-pulmonar e cardíacas como a cardiomiopatia cirrótica. Os objetivos do trabalho são caracterizar as alterações hemodinâmicas e cardíacas de pacientes com cirrose hepática e verificar se houve evidência de cardiomiopatia própria da cirrose hepática. Foram estudados 66 pacientes portadores de cirrose hepática (CH), sendo 54 (82 %) homens e 12 (18 %) mulheres. O grupo controle (CONT) foi constituído de 32 indivíduos sadios, sendo 21 (66 %) homens e 11 (34 %) mulheres. Os indivíduos foram submetidos a exames clínicos e cardíacos por meio de doppler-ecocardiograma. As variáveis estudadas foram analisadas pelo teste ANOVA de duas vias considerando-se os fatores sexo (Masc e Fem) e grupo (CH e CONT) seguido pelo teste de comparações múltiplas de Tukey ao nível de significância de 0,05. As médias e desvios padrões das idades (anos) foram: CH Masc = 49 ± 10; CH Fem = 47 ± 14; CONT Masc = 52 ± 9; CONT Fem = 53 ± 8. Não foram observadas diferenças estatisticamente significantes entre os grupos, quanto a idade. As variáveis... / Cirrhosis is a liver disease characterized by diffuse interstitial fibrosis associated with, regenerative nodules and with intra-hepatic circulation changes. Although the primary damage occurs in the liver, cirrhosis is associated with systemic repercussions. For instance, in the advanced stages of the disease, it has been are described hepatic encephalopatphy syndrome, renal failure such as that accompany the hepato-renal syndrome, pulmonary hypertension observed in portopulmonary syndrome and cardiac alterations. The presence of a specific cardiomyopathy related to the cirrhosis is a matter of controversy. The present study was undertaken to evaluete the cardiac and hemodynamic alterations in patientes suffering from hepatic cirrhosis to analyse the evidence of cirrhotic cardiomyopathy... (Complete abstract click electronic access below)

Objectives: The aim of this pilot study was to compare the changes in oral and gut microbiota, endotoxemia, and systemic and local inflammatory markers following oral interventions in subjects with and without cirrhosis. Methods: Study subjects displaying gingivitis or mild/moderate periodontitis were placed into two groups: with cirrhosis (n= 24) and without cirrhosis (n=21). Each subject received nonsurgical periodontal therapy. Serum, stool and saliva samples were collected prior to and 30 days post-therapy and analyzed for stool/saliva microbiome, MELD score, endotoxin and IL-6 levels. Results: There was no difference in age, gender and the periodontal disease status between groups. At day 30 post therapy, there was a significant reduction in MELD score, endotoxin levels, IL-6 levels and oral and stool microbiome dysbiosis in cirrhotic patients. Conclusion: Endotoxemia and systemic inflammation can be reduced following periodontal therapy, which is likely due to improvement in oral-origin microbiota in both saliva and stool in cirrhotic patients.