Dissertations / Theses on the topic 'Liver'
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1
Tian, Yinghua. "Liver and partial liver transplantation : new models and mechanisms of partial liver graft regeneration /." Zürich, 2005. http://opac.nebis.ch/cgi-bin/showAbstract.pl?sys=000253387.
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Tector, A. Joseph. "Discordant liver xenotransplantation in recipients with liver failure." Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=84439.
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Liver xenotransplantation could eliminate the liver donor shortage, but currently it is not possible because of a lack of understanding of liver xenograft rejection. Hyperacute xenograft rejection is initiated by the binding of preformed naturally occurring xenoreactive antibodies (XNA) to the xenograft endothelium. The XNA bind to the xenograft endothelium, leading to complement-mediated endothelial injury.Liver xenotransplantation will be initially offered to patients with severe liver failure as a bridge to a human liver transplantation. The hypothesis tested in this thesis is that hyperacute rejection of liver xenografts placed into recipients with liver failure will be diminished because of the complement deficiency that accompanies liver failure. The experiments described in this thesis detail the development of an in vitro pig-to-human liver xenotransplant model incubating cultured pig hepatic endothelial cells (PHEC) and human serum in culture. We showed that either classical or alternative complement pathways could initiate endothelial injury. Next we developed the dog-to-pig liver xenograft model and characterized the lethal coagulopathy that results from hyperacute rejection. The coagulopathy results from the lack of function of platelets as well as their disappearance from the circulation. We then used the galactosamine induced liver injury model in porcine recipients of canine liver xenografts to demonstrate that hyperacute rejection in the setting of liver failure is diminished. We showed that; tissue injury, coagulopathy and platelet defect, and endothelial injury were diminished. Our experiments suggested that the cause of the decreased injury was the lack of complement in the pigs with galactosamine induced liver injury since the XNA levels were no different than in control animals. Our final experiments evaluated serum from patients with liver failure and compared the injury caused by incubation with PHEC. Serum from the liver failure patients had similar levels of XNA when compared with normal subjects, but had less complement activity, and less C3 and C4. Incubation of liver failure serum with PHEC caused much less injury and complement activation than serum from control subjects. The results in this thesis suggest that liver failure will have a significant impact on liver xenograft rejection, helping to diminish hyperacut
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He, Qing. "Liver regeneration in rats after liver resection and small for size liver transplantation from living donors." [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=972086595.
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Lindfelt, Jan O. W. "Hepatic nerves in hemostasis and glucose metabolism :." Lund : Dept. of Surgery, Lund University, 1993. http://catalog.hathitrust.org/api/volumes/oclc/39654187.html.
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Hart, Nils Arnaud 't. "Improving liver preservation new strategies in liver procurement and preservation /." [S.l. : Groningen : s.n. ; University Library Groningen] [Host], 2007. http://irs.ub.rug.nl/ppn/30406856X.
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Bikhchandani, Jai. "Extracorporeal liver perfusion as liver support device : a pilot study." Thesis, University of Leicester, 2012. http://hdl.handle.net/2381/11038.
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Introduction: A liver support device can bridge a patient in acute liver failure safely to transplant. An extracorporeal perfused porcine liver (ECLP) circumvents the limitations of hepatocyte based bioartificial liver, but its clinical application has been limited so far due to the potential risk of transmission of porcine endogenous retroviruses. Aim of this study was to develop an ECLP model that can provide artificial hepatic support across a semi-permeable membrane which should block porcine viruses due to its pore size. Methods: 50-60 Kg white landrace pigs treated with standard abattoir animal procedures were used as donors. The liver was perfused with normothermic autologous oxygenated blood using Medtronic BioMedicus BP560 driven centrifugal pump for 6 hours. This ECLP system was used to support a surrogate patient circulation across the filter Evaclio EC4A. Substances like galactose, ammonia, midazolam and para-aminobenzoic acid, were infused into the surrogate patient and their clearance was calculated. The study was designed as test (n=15) vs. control (n=5); with control experiments having no liver in the circuit. Results: After the optimization phase (n=23), we successfully perfused 15 porcine livers with the mean hepatic artery pressure of 87 mm Hg and flows of 1.2 L /min. Retention of Indocyanine green at 15 minutes was 11% in test and 96% in controls. Mean ammonia clearance of 945 mg/min/kg, galactose Vmax of 111.7 mg/min/Kg, hippurate ratio of 91% and a variable midazolam clearance was seen in the test experiments. Conclusion: The study was successful in proving the feasibility of an ECLP model based on abattoir animals that can be utilised for future research work. This model was able to provide adequate support to the surrogate patient across a hollow filter. Further work is needed to show that an ECLP system can be used in an anhepatic animal prior to application in human trials.
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Triantafyllou, Evangelos. "Mechanisms of immune-mediated liver injury in acute liver failure." Thesis, King's College London (University of London), 2017. https://kclpure.kcl.ac.uk/portal/en/theses/mechanisms-of-immunemediated-liver-injury-in-acute-liver-failure(e3e4fdce-9d38-4bdf-b1b4-979f35aef0ae).html.
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Background: Acute liver failure (ALF) is characterized by overwhelming hepatocyte death and liver inflammation where the infiltration of myeloid cells in areas of necrosis is contrasted by immune cell depletion and dysregulation in the systemic circulation. The mechanisms underlying resolution of acute hepatic inflammation are largely unknown to date. In this thesis, I used both human and murine experimental models in order to investigate the impact of Mer Tyrosine Kinase (MerTK) during ALF and examine how the micro-environmental mediator, Secretory Leukocyte Protease Inhibitor (SLPI), governs this immunological response. Methods: Flow cytometry, immunohistochemistry, confocal imaging and gene expression analyses determined the phenotypic, functional and transcriptomic profile and tissue topography of MerTK+ monocytes and macrophages in ALF, healthy and disease controls. The temporal evolution of macrophage MerTK expression and its impact on hepatic resolution was examined in APAP-induced acute liver injury using wild-type (WT) and Mer-deficient (Mer−/−) mice. Furthermore, SLPI effects on hepatic myeloid cells were determined in vitro and in vivo using APAP-treated WT mice. Results: I demonstrate a significant expansion of resolution-like MerTK+HLA-DRhigh cells in both circulatory and tissue compartments of ALF patients. Compared to WT mice, that show an increase of MerTK+MHCIIhigh hepatic macrophages during the resolution phase in ALF, APAP-treated Mer−/− mice exhibit persistent liver injury and inflammation, characterized by a decreased proportion of liver-resident Kupffer cells and increased number of hepatic neutrophils. Both in vitro and in APAPtreated mice, SLPI reprograms macrophages towards resolution responses through induction of a MerTK+HLA-DRhigh phenotype which promotes neutrophil apoptosis and their subsequent clearance. Conclusions: The work presented in this thesis has identified a prorestorative, MerTK+, macrophage phenotype that evolves during the resolution phase of APAP-induced ALF and represents a novel immunotherapeutic target to promote resolution responses following acute liver injury.
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Foss, Aksel. "Liver regeneration and partial liver transplantation an experimental study in the rat /." Lund : Dept. of Surgery, Lund University, 1992. http://books.google.com/books?id=d_BqAAAAMAAJ.
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Li, Jiangning. "Functional genomics and liver regeneration : transcriptional regulation on rapid liver regeneration /." Thesis, Connect to this title online; UW restricted, 2006. http://hdl.handle.net/1773/6351.
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Kung, Janet Wui Cheung. "Investigating the liver progenitor cell niche in the developing human liver." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/25953.
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Liver cirrhosis places an increasing burden on healthcare worldwide. Currently the only treatment is liver transplantation. Whilst liver transplant has a relatively good five-year survival, donor organ shortage costs many lives every year and results in lifelong immunosuppression. Alternative treatments are thus urgently needed. It is with this background that there is understandable interest for the development of stem cell therapies for liver regeneration. The identification of putative liver stem cells has brought closer the previously separate fields of liver ontology, regeneration, and carcinogenesis. Significant overlaps in the regulation of these processes are now being described. For example, studies in embryonic liver development have already provided the basis for directed differentiation of human embryonic stem cells and induced pluripotent stem cells into hepatocyte-like cells. As a result, the understanding of the cell biology of proliferation and differentiation in the liver has been improved. This knowledge can be used to improve the function of hepatocyte-like cells for drug testing, bio-artificial livers, and transplantation. In parallel, the mechanisms regulating cancer cell biology are now clearer, providing fertile soil for novel therapeutic approaches. Recognition of the relationships between development, regeneration, and carcinogenesis, and the increasing evidence for the role of stem cells in all of these areas, has sparked fresh enthusiasm in understanding the underlying molecular mechanisms and has led to new targeted therapies for liver cirrhosis and primary liver cancers. Human liver progenitor cells (LPCs) have therapeutic potential but their in vitro culture results in inadequate differentiation, function, and phenotypic instability reflecting an incomplete understanding of in vivo processes. LPCs can be robustly isolated from second trimester human foetal livers by immunoselection for EpCAM+/CD29+/CD49d+/CD49e–/CD235a–/CD45– cells. Expression profiling of mRNA and microRNA in human foetal LPCs was performed and compared with mature human hepatocytes and human embryonic stem cells undergoing hepatocytic differentiation. Foetal LPCs exhibit a distinct transcriptome profile consistent with a stem cell signature, cell division, and some liver-specific functions. Bioinformatic integration of microRNA and mRNA datasets revealed that microRNAs up-regulated in LPCs targeted genes involved in metabolic processes implying repression of the mature hepatocyte phenotype. Control of LPC gene expression therefore occurs at both transcriptional and, via microRNAs, post-transcriptional levels. Furthermore, transcription factor binding site analyses revealed enriched E2F1 motif in gene and microRNA promoters suggesting feedback control in determining LPC fate. Foetal LPCs were capable of differentiation to a hepatocytic phenotype in the presence of appropriate paracrine signals provided by EpCAM– non-parenchymal cells (NPCs), which consist mainly of endothelial cells and hepatic stellate cells. Fibronectin, despite being produced in abundance by EpCAM– NPCs, had no effect on LPC synthetic function in vitro. The expression of fibronectin in the perisinusoidal space suggests its potential role of modulating cross-talk between hepatoblasts/hepatocytes, liver sinusoidal endothelial cells, and hepatic stellate cells. Fibronectin expression in the portal vein mesenchyme and laminin α5 expression along the ductal plate suggest that both matrix molecules, located in close proximity to LPCs, may be important in supporting the LPC niche. Findings in this work provide insight into the regulation of the human foetal LPC functional phenotype, bringing stem cell-based therapies for liver disease one step closer.
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Chan, See-ching. "Donor perspective of right lobe adult-to-adult live donor liver transplantation." Click to view the E-thesis via HKUTO, 2005. http://sunzi.lib.hku.hk/hkuto/record/B34736414.
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Chan, See-ching, and 陳詩正. "Donor perspective of right lobe adult-to-adult live donor liver transplantation." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B34736414.
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Mathur, Sachin. "Studies of prognosis and nutritional intervention in liver cirrhosis and liver transplantation." Thesis, University of Auckland, 2010. http://hdl.handle.net/2292/6892.
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In patients with chronic liver disease protein-energy malnutrition (PEM) is a common finding. These patients are predisposed to higher rates of in-hospital mortality, hepatic encephalopathy and infectious complications. In cirrhotic patients awaiting orthotopic liver transplantation (OLT), a strong correlation is noted between worsening PEM and higher post-transplant complications and reduced survival. Some gaps in the literature exist with regard to PEM in cirrhosis. This thesis aimed to address some of these issues: the prognostic utility of markers of PEM; the therapeutic benefit of a specialised immunonutritional supplementation in the peri-OLT setting; and whether PEM returns to normal in the long term, following successful OLT. To assist with these aims, accurate assessment of PEM is required. The body composition laboratory (BCL) offers state of the art methods to assess nutritional status. Dual-energy x-ray absorptiometry (DXA) and in vivo neutron activation analysis (INAA) allow for accurate assessment of body weight, fat, protein and water content, all of which are deranged in cirrhotic patients. In a longitudinal analysis of cirrhotic patients’ serum sodium, hydration state and resting energy expenditure (REE) independently predicted transplant-free survival (TFS) when compared to the Child-Pugh and MELD scores, which are the established prognostic tools in liver cirrhosis. Impact (Nestle), a form of immunonutrition (IN) containing omega-3 fatty acids, arginine and nucleotides, was provided to cirrhotic patients awaiting liver transplantation in a double-blind randomised controlled trial (RCT). When compared to an isocaloric isonitrogenous control feed, pre-OLT body protein gain, post-OLT body composition changes and clinical outcomes were similar. A sub-group of patients also underwent whole-body protein turnover measurements to establish any underlying mechanism of action for IN. Patients were catabolic, which did not improve significantly after fourteen days of IN. Finally, in a cohort of patients followed for three or more years after OLT, body composition had returned to normal, although quality of life (QOL) was reduced when compared to the normal population. In conclusion, the studies from this thesis have shown serum sodium, hydration and REE to be significant predictors of TFS in cirrhotic patients. IN was not superior to an iso-caloric iso-nitrogenous control feed in the peri-OLT setting, and long-term survivors after OLT were restored to normal nutritional status.
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Poli, G. "Biochemical studies on CC14̲-induced liver injury using isolated rat liver cells." Thesis, Brunel University, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.379250.
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Urdzik, Jozef. "Colorectal Cancer Liver Metastases : Effects of Chemotherapy on Liver Parenchyma and Resections." Doctoral thesis, Uppsala universitet, Institutionen för kirurgiska vetenskaper, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-233790.
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Current multimodal treatment of colorectal cancer liver metastasis often combines liver resections with preoperative chemotherapy with a 5-year survival of 40-50%. Preoperative chemotherapy includes conversion of initially non-resectable situation and control of micrometastatic disease. Despite its potential advantages also problems with associated steatosis, steatohepatitis and sinusoidal injury has been discussed. Paper I focused on prospective steatosis evaluation prior to resections using proton MR spectroscopy, most sensitive non-invasive method. Proton MR spectroscopy showed high concordance with digital quantification of steatosis and was also able to predict steatohepatitis with 100% sensitivity and 89% specificity without knowing lobular inflammation or hepatocyte ballooning. Paper II focused on portal vein hemodynamics changes in patients treated with oxaliplatin-based treatment and with sinusoidal injury. Magnetic resonance imaging flowmetry demonstrated portal vein dilatation associated with oxaliplatin treatment. Patients with SI showed a tendency towards decreased mean portal flow velocity. Portal vein flow was not changed. This may indicate that SI is associated with an increased resistance to blood flow in the liver parenchyma and stasis in splanchnic system. Paper III attempted to enlighten the effects of FOLFOX treatment on human liver tissue 6 weeks after treatment cessation by quantification of protein expression changes using label-free global proteome analysis. Deep proteome analysis identified 5891 proteins, where machine learning algorithm identified 3% of classifying proteins, associated with changes in DNA replication through upregulation of the minichromosome maintenance complex and with the innate immune response. Significant changes were observed in 1% of proteins, associated with DNA replication and cell cycle entry. Results support the hypothesis that liver has already regenerated from the FOLFOX treatment injury after 6 weeks. Paper IV aimed to identify possible patient, disease and chemotherapy characteristics associated with liver specific and severe general complications in a retrospective single centre cohort composed of 516 consecutive resections. Chemotherapy with more than 4 cycles of oxaliplatin was associated with post-hepatectomy hemorrhage. Underlying liver disease and diabetes mellitus were associated with 90-day mortality. Size of resection, intraoperative blood loss and transfusions were verified as independent predictors of liver specific complications to resections.
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Spanos, Christos. "Quantitative liver proteomics for biomarker discovery in non-alcoholic fatty liver disease." Thesis, University of Surrey, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.616323.
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Non-alcoholic fatty liver disease (NAFLD) is now the most common liver disease worldwide. Given that NAFLD can progress from steatosis to non-alcoholic steatohepatitis (NASH), fibrosis and potentially hepatocellular carcinoma, early diagnosis and accurate disease staging are primary clinical concerns. Hypothesizing that a subset of liver proteins will exhibit differential expression in NAFLD and that these proteins may represent candidate disease biomarkers; the aims of this project were to use proteomics to identify differentially expressed proteins both in an in vitro and an in vivo model of NASH. Preliminary studies developed and characterised both models used here; experiments utilized a relative quantitative proteomic approach with isobaric tags for relative and absolute quantitation labelling combined with nano-liquid chromatography and tandem mass spectrometry.
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Guthrie, Joy D. "Assessing Doppler-Derived Pressure Gradients and Liver Echogenicity to Predict Liver Disease." ScholarWorks, 2011. https://scholarworks.waldenu.edu/dissertations/969.
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Liver disease causes an estimated 36,000 deaths in the United States each year. Currently, to detect liver disease, an invasive biopsy is required. Other, less invasive diagnostic alternatives are needed. The purpose of this study was to assess the efficacy of a modified form of sonographic screening, including portal, hepatic, and splenic venous pressure, hepatic venous waveform analysis, portal vein diameter, and echogenicity of liver parenchyma in predicting liver disease. The study was based on conversion of a velocity measurement to a pressure gradient, allowing a fluid comparison between known catheterization venous pressures and sonographic Doppler-derived pressure gradients. This study was a secondary data analysis of a data set from 546 patients who received abdominal sonograms at a medical facility in the western United States between March 2010 and December 2010. The dependent variable was liver disease and the independent variables were ECHOGRADE, hepatic venous waveform (HVW), splenic vein pressure gradient (SVPG), modified portal vein pressure gradient (MPVPG), and hepatic vein pressure gradient (HVPG). Logistic regression was used to analyze the data. ECHOGRADE, HVW, and MPVPG in males were found to be statistically significant in detecting liver disease, supporting the theoretical framework and thus documenting a novel use of Doppler for the detection of liver disease. The social change significance of these results is to provide clinicians with an alternative, noninvasive method of diagnosing early liver disease before it progresses into chronic liver disease. With earlier detection, severe adverse health outcomes leading to irreversible liver cirrhosis may be avoided.
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Lopez, Alexandre. "Liver preservation : New markers of viability for normal and steatotic liver grafts." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS067.
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Les foies dits "marginaux" sont utilisés pour répondre à la pénurie d’organes et à l’augmentation du nombre de patients sur liste d’attente. Tout l’enjeu aujourd’hui est de réussir à diminuer les complications post-opératoires souvent associées à ces greffons en améliorant la qualité de leur préservation. L’estimation de la qualité d’un foie, afin de prédire sa reprise de fonction, est souvent réalisée chez le donneur. Cependant, bien qu’elle influe directement sur la qualité du foie, les conséquences liées à la période d’ischémie ne sont que très rarement considérées car il n’existe pas de marqueurs spécifiques pour les évaluer en dehors d’un système de perfusion normothermique.Le glycocalyx, une couche polysaccharidique présente à la surface des cellules endothéliales, a déjà démontré son potentiel comme biomarqueur pour évaluer la qualité des foies. Chez des foies stéatosiques de rats, une diminution des lésions d'ischémie-reperfusion a été observée lorsque les composants du glycocalyx étaient mieux préservés avec la solution IGL-1, potentiellement due à la présence de l'agent oncotique PEG35. Ces résultats ont été confirmés en préservation dynamique, chez des foies non-steatosiques de rats, avec une protection améliorée des foies soumis à une perfusion hypothermique oxygénée (HOPE) avant la phase d'ischémie froide. Dans un contexte pré-clinique, nous avons pu démontrer qu’après 6h de perfusion normothermique, 3 foies humains sur 11, initialement refusés pour la transplantation, auraient potentiellement pu être transplantés en se basant sur des critères de viabilité évalués au cours de la perfusion.Une meilleure évaluation de la préservation des greffons hépatiques grâce au glycocalyx, tout en diminuant les risques associés aux foies marginaux grâce aux machines de perfusion normothermiques, pourrait permettre de faire face aux besoins croissant d’organes"Marginal" livers are used to respond to the shortage of organs and the increase in the number of patients on the waiting list. The challenge is to successfully reduce the post-operative complications associated with these grafts by improving the quality of organ preservation. Assessing the quality of a liver to predict its function recovery is often performed while the organ is still in the donor. However, although the ischemia period directly affects the quality of the liver, the consequences of that period for the liver are rarely considered. No markers exist to evaluate those consequences, beyond a system of perfusion.Glycocalyx, a polysaccharidic layer at the surface of endothelial cells, has already proven its potential as a biomarker to evaliate the quality of livers. In steatotic rat livers, ischemia-repefusion injury decreased when glycocalyx components were better preserved in static conditions with preservation solution IGL-1, potentially due to the oncotic agent PEG35. These results were confirmed in dynamic preservation, with an improved liver protection when livers were subjected to hypothermic oxygenated perfusion (HOPE) before static cold storage. In pre-clinical settings, we also demonstrated that after 6h of normothermic perfusion, 3 out of 11 human livers, originally discarded for the transplantation, could have been potentially transplanted based on their viability criteria during perfusion.Better evaluation of hepatic graft preservation using glycocalyx, together with reducing the risks associated with marginal livers using normothermic perfusion machines, could help to meet the growing need for organs
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Thomas, Cynthia W. "The lives of liver recipients in the long-term : a descriptive-exploratory study /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2008.
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Thesis (Ph.D. in Nursing) -- University of Colorado Denver, 2008.Typescript. Includes bibliographical references (leaves 192-203). Free to UCD Anschutz Medical Campus. Online version available via ProQuest Digital Dissertations;
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Niemelä, Onni. "Aminoterminal propeptide of type III procollagen and basement related antigens in alcoholic liver disease." Oulu : University of Oulu, 1985. http://catalog.hathitrust.org/api/volumes/oclc/14472875.html.
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Sanders, Jennifer Ann. "Regulation of the c-Myc/Max/Mad network during liver development and regeneration /." View online version; access limited to Brown University users, 2005. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:3174671.
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Pike, Kenneth Charles. "Allocating life : the selection of liver transplant patients /." Thesis, Connect to this title online; UW restricted, 1996. http://hdl.handle.net/1773/8917.
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Poon, Tung-ping Ronnie. "Surgical strategies to improve long-term survival after hepatectomy for hepatocellular carcinoma." Hong Kong : University of Hong Kong, 1999. http://sunzi.lib.hku.hk/hkuto/record.jsp?B20933915.
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Lo, Chung-mau. "Application of living donor liver transplantation to adult recipients in Hong Kong /." Hong Kong : University of Hong Kong, 1998. http://sunzi.lib.hku.hk/hkuto/record.jsp?B20017492.
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Huda, Amina. "Employment after liver transplantation." Diss., Search in ProQuest Dissertations & Theses. UC Only, 2010. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3398878.
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Quant, Patti A. "Control of liver ketogenesis." Thesis, University of Cambridge, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.293878.
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Jamieson, N. V. "Liver preservation for transplantation." Thesis, University of Cambridge, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.605054.
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Grover, Vijay Paul Bob. "Neuroimaging in liver disease." Thesis, Imperial College London, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.520951.
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Al-Nbaheen, May Salem. "Liver specific gene expression." Thesis, University of Bath, 2002. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.760790.
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Bayard, Max, Jim Holt, and Eileen Boroughs. "Nonalcoholic Fatty Liver Disease." Digital Commons @ East Tennessee State University, 2006. https://dc.etsu.edu/etsu-works/6487.
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Tirnitz-Parker, Janina Elke Eleonore. "Primary culture and immortal cell lines as in vitro models to evaluate the role of TWEAK signalling in hepatic oval cells /." Connect to this title, 2007. http://theses.library.uwa.edu.au/adt-WU2008.0039.
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AOKI, KUNIO, RYUICHIRO SASAKI, and ZHU-MIN HUANG. "Trends in Mortality from Primary Liver Cancer, Cirrhosis of the Liver, Virus Hepatitis, and Other Liver Diseases 1968-1984 in Japan." Nagoya University School of Medicine, 1987. http://hdl.handle.net/2237/17497.
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CATALANO, GIORGIA. "Human liver stem cells and derived products in experimental models of liver ischemia reperfusion injury and of liver isolated normothermic perfusion." Doctoral thesis, Politecnico di Torino, 2018. http://hdl.handle.net/11583/2711047.
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Ischemia reperfusion injury (IRI) is an antigen-independent inflammatory event that affects several
clinical settings, including surgical procedures such as liver resection and liver transplantation. IRI
is still a major concern in the transplantation setting, causing up to 10% of early graft failure and
leading to a higher incidence of acute and chronic rejection. IRI is initiated by Kuppfer cells and
hepatocytes through a massive production of reactive oxygen species (ROS) during the ischemic
phase and, in a major degree, during the post-reperfusion phase. ROS directly damage hepatocytes and endothelial cells and promote the recruiment of neutrophils and T-cells, starting an inflammatory cascade that triggers apoptosis and necrosis.
Human Liver Stem Cells (HLSC) have been identified as a population of pluripotent resident liver
cells able to express markers characteristic of the mesenchymal lineage (CD73, CD90, CD29,
CD44) together with hepatic markers (alpha-fetoprotein, cytokeratin 18, cytokerain 8 and albumin),
suggesting a partial hepatic commitment. HLSC share self-renewal properties with mesenchymal
stem cells and can actively take part to tissue remodeling and liver regeneration. We found that
HLSC are able to localize within the injured tissue and promote liver regeneration in a murine
model of fulminant liver failure and to generate a functional “humanized liver-like tissue” when
injected in rat acellular liver scaffolds. Growing evidence suggests that the biological effects of
stem cells on neighboring cells are mediated by paracrine mechanisms including the release of
extracellular vesicles (EV). EV are an heterogeneous population of cell-secreted vesicles
originating from the endosomal compartment or from direct budding of plasma membrane that are
able to modify the phenotype and function of neighboring cells. The regenerative effects of EV are
well documented and ascribed to a horizontal transfer of proteins, lipids and, above all, specific
subsets of mRNA and miRNA. In a rat model of 70% hepatectomy, animals treated with Human
Liver Stem Cells-derived Extracellular Vesicles (HLSC-EV) revealed a significant reduction of
liver injury and higher regeneration rate of the remnant liver after surgery .
The effect of HLSC-EV was investigated on two different experimental models:
First Project
We set up a short-duration model of ex vivo isolated rat liver Normothermic Machine Perfusion
(NMP) in which oxygen delivery was kept suboptimal through a low hemoglobin
content in the perfusate. In this model, we investigated whether adding HLSC-EV to the circuit
could result in i) their rapid uptake by the liver, and ii) an appreciable reduction of the hypoxic
tissue injury.
Second Project
An in-vivo model of IRI was set up in mice. The aim of this study was to investigate the effects of
systemic administration of HLSC-EV on tissue injury after partial clamping of the hepatic hilum
(70%) .
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Lam, Shi. "The significance of hepatic stellate cell activation in small-for-size fatty liver graft injury /." View the Table of Contents & Abstract, 2007. http://sunzi.lib.hku.hk/hkuto/record/B3829686X.
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Fan, Sheung-tat. "Adult-to-adult live donor liver transplantation using right lobe graft : toward a perfect technical design /." Hong Kong : University of Hong Kong, 2002. http://sunzi.lib.hku.hk/hkuto/record.jsp?B2520581x.
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Warren, Alessandra. "Hepatic sinusoidal cells in liver immunology and ageing." Thesis, The University of Sydney, 2005. https://hdl.handle.net/2123/27902.
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The liver has a key role both from a metabolic and an immunological viewpoint. It is involved in the metabolism, or degradation of different molecules absorbed by the intestine, including xenobiotics, drugs and lipids, the synthesis and turnover of plasma proteins, the production of bile and the storage of glycogen and vitamin A. Unique amongst solid organs, the sinusoidal endothelium of the liver is perforated with pores, or fenestrations,
and is not separated from hepatocytes by a basal lamina. It has been proposed that the fenestrations, also termed the ’liver sieve’, function as a bio-filter allowing free diffusion of small molecules (less than 100 nm in diameter) from the blood to the hepatocytes and Vice versa. Changes in these structures, as seen in ageing, could have important effects on hepatic function and in particular lipid metabolism.
The liver also has unique immunological functions including T-cell
activation and tolerance. This thesis explores potential new roles of the
fenestrated sinusoidal endothelium in some aspects of liver immunology and
ageing.
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Söderdahl, Gunnar. "Liver transplantation and the role of adjuvant therapy for advanced primary liver tumours /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-579-8/.
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Akingbasote, J. A. "The potential role of liver sinusoidal endothelial cells in drug-induced liver injury." Thesis, University of Liverpool, 2016. http://livrepository.liverpool.ac.uk/3005113/.
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Liver sinusoidal endothelial cells (LSEC) constitute a unique population of endothelial cells with specialised liver-specific morphologic features and functions. LSEC are the only endothelial cells with fenestrations and which lack an organised basement membrane. They are involved in hepatic stellate cell (HSC) quiescence, endocytosis of small particles, selective transfer of substances from the blood, in the hepatic sinusoid, to the parenchymal cells and in liver regeneration. As the group of cells that form the inner lining of the capillaries of the liver sinusoids, and being the first to be in contact with blood-borne particles, pathogens, and xenobiotics, they are prone to the deleterious effects of these. The aims of this thesis were to investigate the unique features of human liver sinusoidal endothelial cells (HLSEC) in comparison with endothelial cells from other vascular beds, evaluate the sensitivities of HLSEC to a range of hepatotoxic drugs, including small-molecule receptor tyrosine kinase inhibitors (RTKIs), such as regorafenib, and to explore the role of HLSEC in a triculture human liver microtissue. Results obtained from this study showed that HLSEC expressed phenotypic features of vascular and lymphatic endothelial cells, particularly vascular endothelial growth factor receptor 2 (VEGFR-2) which could be activated by VEGF-A to stimulate cell proliferation, migration and tubular morphogenesis. HLSEC also expressed functional VEGFR-3. Transcriptomic analysis indicated that HLSEC expressed specialised genes, such as plasmalemma vesicle associated protein (PLVAP), that support its liver-specific structure and functions. HLSEC were more sensitive to a range of small-molecule receptor tyrosine kinase inhibitors than other hepatic cells. (primary human hepatocytes [PHH] and human hepatic fibroblasts [HHF]) and endothelial cells from other vascular beds (human dermal microvascular endothelial cells and human dermal lymphatic endothelial cells). Regorafenib inhibited the activation of VEGFR-2 thereby abrogating cell proliferation, migration, tubular morphogenesis as well as upregulation of angiocrine factors involved in liver regeneration following activation by vascular endothelial growth factor A (VEGF-A). Regorafenib also caused a disruption of cytoskeletal structure of HLSEC and induced apoptosis via activation of caspase 3. Triculture liver microtissues formed with PHH, HLSEC and HHF were vascularised with higher expression of liver-specific drug-metabolising enzymes in comparison with the same combination of cells cultured as a monolayer. However, metabolic competence of triculture liver microtissues was significantly lower than in their monoculture counterparts (consisting of PHH only). This study has further confirmed the uniqueness of HLSEC as a specialised endothelial cell adapted to its anatomical role, which could respond to a range growth factors to initiate endothelial cell-specific functions. It has also been demonstrated that HLSEC are a direct target of hepatotoxic drugs. Triculture liver microtissues generated with PHH, HLSEC and HHF showed less metabolic competence than their PHH-only counterparts. Future studies need to investigate the role of RTKIs in vascular toxicity using in vivo models of sinusoidal obstruction syndrome (SOS) and liver regeneration. Finally, it would be informative to investigate the possibility of identifying HLSEC-specific biomarkers of liver toxicity.
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Yasuda, Katsutaro. "A nonhuman primate model of liver fibrosis towards cell therapy for liver cirrhosis." Kyoto University, 2020. http://hdl.handle.net/2433/258975.
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Yamagami, Kazuhiko. "Heat shock preconditioning ameliorates liver injury following normothermic ischemia-reperfusion in steatotic rat livers." Kyoto University, 1999. http://hdl.handle.net/2433/181689.
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Ibrahim, Sara [Verfasser], Achim [Akademischer Betreuer] Göpferich, and Thomas S. [Akademischer Betreuer] Weiß. "The role of liver regeneration-associated protein ALR, Augmenter of Liver Regeneration, in cholestatic liver diseases / Sara Ibrahim ; Achim Göpferich, Thomas S. Weiß." Regensburg : Universitätsbibliothek Regensburg, 2019. http://d-nb.info/1201884012/34.
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Barnes, Mark Aaron Jr. "MACROPHAGE MIGRATION INHIBITORY FACTOR AND LIVER DISEASE: THE ROLE OF MIF IN ALCOHOL-INDUCED LIVER INJURY AND CARBON TETRACHLORIDE (CCI4)-INDUCED LIVER FIBROSIS." Case Western Reserve University School of Graduate Studies / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=case1396429556.
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Kyriakides, Michael. "Metabolic phenotyping applied to pre-clinical drug induced liver injury and acute liver failure." Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/29110.
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Liver disease is a prevalent clinical challenge caused by a variety of factors including viral infections and xenobiotic overdose. Improving our mechanistic understanding of disease development will lead to an improved stratification of patients and ultimately a better prognosis. This thesis addresses the role of metabonomics in providing insight into a variety of preclinical models and a clinical study. The metabolic phenotype of preclinical models of paracetamol (APAP) and methotrexate (MTX) toxicity were characterised, together with the study of clinical samples from decompensated cirrhosis, acute on chronic liver failure (ACLF) and acute liver failure (ALF) patients. A comparative metabonomic approach was applied to study the metabolic consequences following administration of APAP and its non-hepatotoxic isomer; N-acetyl-m-aminophenol (AMAP), in mice. The analysis revealed an APAP-induced hepatotoxicity through mitochondrial dysfunction which was characterized by an upregulation of glycolysis as well as the inhibition of beta-oxidation and the Krebs cycle. The metabolic and toxic effects of MTX were investigated in healthy rats and in a model of non-alcoholic steatohepatitis (NASH; as modelled by the methionine choline deficient diet). MTX was shown to have an enhanced toxicity in the context of NASH, which was associated with unique metabolic changes. The clinical work revealed that the serum metabolic phenotypes of clinical decompensated cirrhosis, ACLF and ALF patients were also each characterized by unique metabolic perturbations. The ALF phenotype was associated with the most metabolic changes and consisted of markers of oxidative and energetic stress, as well as markers of amino acid metabolism dysfunction. Subsequently, the novel serum metabolic profiling of the hepatic vein, hepatic portal vein and peripheral artery of patients during liver transplantation aimed to characterize the hepatic disease microenvironment, which was discovered to mainly consist of a perturbed amino acid metabolism.
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Orbach, Sophia Michelle. "Multi-Cellular Organotypic Liver Models for the Investigation of Chemical Toxicity and Liver Fibrosis." Diss., Virginia Tech, 2018. http://hdl.handle.net/10919/93313.
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The liver is responsible for lipid and glucose metabolism, protein and bile synthesis and the biotransformation of xenobiotics. These functions, performed by hepatocytes, are dependent on heterotypic interactions with other liver cell types and the stratified microarchitecture of the organ. In vitro liver models provide insights into the role of each cell type and perturbations upon external stimuli. Despite the dissimilarities to in vivo and rapid dedifferentiation, most liver studies utilize hepatocyte monocultures. These models lack heterotypic interactions causing inaccurate assessments of toxicity and disease. Only a limited number of 3D hepatic models incorporate the major liver cell types, and these cultures primarily focus on the hepatocyte response. We have developed 3D liver models that include all major hepatic cell types and recapitulate the layered architecture of the organ. These models maintain hepatic functions for up to four weeks and can be used to isolate the role and response of each cell type. We used these models to study two critical aspects of the organ -- acute hepatotoxicity and liver fibrosis.
There are tens of thousands of chemicals with undetermined effects on the human body. High concentrations of xenobiotics can cause acute liver damage and failure. Liver impairment can result in multiple organ failure, hepatic encephalopathy and death. Therefore, it becomes critically important to investigate hepatotoxicity in a time, cost and resource effective manner. Our 3D liver models were validated for hepatotoxicity testing with acetaminophen, a prototypic drug. We then adapted and optimized the models for high-throughput hepatotoxicity testing with automated procedures and primary human hepatic cells.
Liver fibrosis and cirrhosis are well-established consequences of chronic chemical exposure, infection and alcoholism. The initiating factors, end stages and resolution of fibrosis have been extensively studied. However, there is minimal information on the role of the local microenvironment in the progression of the disease from diseased to healthy tissue. We designed 3D liver cultures with a mechanical gradient to gradually model this transition through spatial and temporal perspectives. These findings demonstrate the versatility and accuracy of these 3D hepatic models in the investigation of liver toxicity and fibrosis.Ph. D.
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Maetani, Yoji. "Factors influencing liver regeneration following living-donor liver transplantation of the right hepatic lobe." Kyoto University, 2003. http://hdl.handle.net/2433/148765.
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Köhn, Julia. "Characterisation of liver progenitor cells and their microenvironment during chronic liver disease and hepatocarcinogenesis." Thesis, Curtin University, 2016. http://hdl.handle.net/20.500.11937/48824.
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The studies in this thesis aimed to characterise liver progenitor cells and their microenvironment during chronic liver injury conditions. A comprehensive comparison of the two common murine chronic liver disease models, CDE versus TAA, was performed. Parameters such as hepatocyte health, inflammation, fibrosis and the LPC response were investigated during stages of injury induction, establishment, maintenance, progression and carcinogenesis. Furthermore, the relationship between LPCs and HCC development in humans was investigated in a retrospective study.
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Germani, Giacomo. "Predicting acute cellular rejection after liver transplantation: form liver function test to immune monitoring." Doctoral thesis, Università degli studi di Padova, 2013. http://hdl.handle.net/11577/3426180.
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In recent years, the main end point of immunosuppressive therapy after liver transplantation has moved from the prevention of acute cellular rejection (ACR) toward the preservation of long-term graft function and prevention of immunosuppression-related side effects. This approach requires an optimal management of immunosuppressive therapy according to patient risk factors. However, the concentration of immunosuppressive drugs in the serum of patients, which is generally used as a surrogate for the level of immunosuppression, does not provide information about the magnitude of suppression of the immune system. Therefore a reliable marker for the development of ACR, or to predict patients who could tolerate reduced immunosuppression, would be crucial for improving post-transplant management of liver transplanted patients.
The aims of the studies presented in this thesis were: 1) to assess the incidence of ACR after liver transplantation, to identify potential risk factors for ACR, and to evaluate the impact of ACR and its histological severity on outcomes; 2) to evaluate the role of liver function tests and blood eosinophil count as potential biomarkers for ACR after liver transplantation, with special attention on prediction
of histologically proven moderate and severe ACR; 3) to evaluate the expression of specific immunological markers for ACR in patients before and after liver transplantation.
The results of the studies showed that patient and graft survival at 1, 5 and 10 years after liver transplantation were not different with respect to presence or absence of ACR. Only untreated moderate/severe ACR was associated with increased death/graft loss using adjusted Cox regression analysis, whereas mild ACR, whether treated or not, had no effect. With regards to the evaluation of potential markers of ACR, despite peripheral eosinophilia was not sufficiently predictive of moderate/severe ACR, the delta in eosinophil count between the first and second biopsies was the only independent predictor of histological improvement, irrespective of whether bolus steroids were used.
Lastly, we demonstrated that the increased expression of C28 and C38 on both CD4+ and CD8+ T cells and the increased levels of IL-17. These alterations of immune system could be used routinely in clinical practice to assess the immune status of liver transplanted patients and to properly manage immunosuppressive therapyLo scopo principale della terapia immunosoppressiva dopo trapianto di fegato è passato dalla prevenzione del rigetto acuto alla preservazione della funzionalità a lungo termine dell’organo trapiantato e alla prevenzione degli effetti collaterali dovuti alla terapia immunosoppressiva. Per perseguire tale scopo è necessaria una gestione ottimale della terapia immunosoppresiva stessa. Tuttavia, la misurazione dei livelli ematici dei farmaci immunosoppressori, generalmente utilizzati come surrogato dei livelli di immunosoppressione, non fornisce informazioni relative alla reale intensità della soppressione del sistema immunitario. Pertanto l’individuazione di marcatori biologici di rigetto acuto e/o di tolleranza risulta fondamentale per poter migliorare la gestione della terapia immunosoppressiva dopo-trapianto di fegato. Gli scopi degli studi riportati in questa tesi sono: 1) determinare l’incidenza e gli eventuali fattori di rischio di rigetto acuto dopo trapianto di fegato, valutare in che l’influenza del rigetto acuto e della sua severità istologica sulla sopravvivenza dell’organo e del paziente dopo trapianto di fegato; 2) valutare il ruolo degli indici di funzionalità epatica e della conta eosinofilica ematica come potenziali marcatori biologici di rigetto acuto dopo trapianto di fegato, in particolare di grado moderato/severo; 3) valutare, prima e dopo trapianto di fegato l’espressione di specifici marcatori immunologici di rigetto acuto. I risultati degli studi condotti hanno evidenziato come pazienti con diagnosi di rigetto acuto alla biopsia di protocollo presentino una sopravvivenza di organo e paziente, a 1, 5 e 10 anni dal trapianto di fegato, del tutto sovrapponibile a quella di pazienti senza evidenza istologica di rigetto acuto alla biopsia di protocollo. L’insorgenza di rigetto acuto di grado moderato/severo non sottoposto a trattamento farmacologico è tuttavia associata ad aumentata incidenza di decesso o perdita dell’organo post-trapianto. Nel valutare potenziali marcatori biologici di rigetto acuto, abbiamo dimostrato che nonostante la conta eosinofilica periferica non sia sufficientemente predittiva per lo sviluppo di rigetto acuto post-trapianto, la differenza nella conta eosinofilica tra la prima e la seconda biopsia epatica può essere considerato un fattore predittivo di miglioramento istologico, indipendentemente dall’utilizzo o meno di terapia con boli steroidei. Non è stata invece evidenziata alcuna associazione tra l’alterazione degli indici di funzionalità epatica e l’insorgenza di rigetto acuto. Infine, è stato dimostrato che l’insorgenza di rigetto acuto risulta associata ad aumentata espressione di CD28 e CD38 sia sui linfociti T CD4+ che CD8+ e ad un aumento dei livelli di IL-17. Tali alterazioni del sistema immunitario potrebbero essere utilizzate nella pratica clinica per valutare lo stato di soppressione del sistema immunitario in pazienti sottoposti a trapianto di fegato con il fine ultimo di una gestione ottimale e personalizzata della terapia immunooppressiva
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Aguiar, Maria Ãsis Freire de. "Liver transplantation: the meaning for those that live the wait for the surgical procedure." Universidade Federal do CearÃ, 2007. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=626.
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CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel SuperiorO objetivo do transplante de fÃgado à aumentar a sobrevida de pacientes portadores de doenÃas hepÃticas irreversÃveis agudas e crÃnicas, alÃm de proporcionar melhor qualidade de vida. O interesse em prestar uma atenÃÃo em saÃde mais qualificada ao paciente em espera pelo transplante de fÃgado nos instigaram a nos aproximar mais da realidade vivenciada por ele, considerando que a compreensÃo da situaÃÃo vivida favorece uma assistÃncia mais humanizada e individualizada, contribuindo, ainda, para a construÃÃo do conhecimento em enfermagem e para a transformaÃÃo da prÃtica do enfermeiro. Objetivamos apreender o significado do transplante de fÃgado para o paciente em prÃ-transplante, atravÃs da caracterizaÃÃo dos pesquisados nos aspectos sÃcio-demogrÃficos e padrÃes clÃnicos; da identificaÃÃo dos sentimentos, crenÃas, valores e atitudes vivenciadas; e da identificaÃÃo de estratÃgias de enfrentamento para condiÃÃo vivenciada. Pesquisa de abordagem qualitativa, tendo como referencial teÃrico-metodolÃgico a Teoria HumanÃstica de Paterson e Zderad. Participaram do estudo dezoito pacientes inscritos no programa de transplante de fÃgado e acompanhados no Centro de Transplantes de FÃgado do Cearà â CTFC. Os dados foram coletados atravÃs de prontuÃrios, observaÃÃo nÃo-participante e entrevista. A anÃlise dos dados teve por base os preceitos do processo da Enfermagem FenomenolÃgica, utilizando quatro fases: a preparaÃÃo para vir-a-conhecer os pacientes que aguardam um transplante de fÃgado, conhecendo intuitivamente os pacientes, conhecendo cientificamente os pacientes e sÃntese complementar das realidades conhecidas. Desse processo, emergiram as unidades temÃticas com as categorias histÃria da doenÃa, sentimentos, enfrentando a condiÃÃo vivenciada, significado, expectativas e percepÃÃo do futuro. Identificamos o termo ânova vidaâ como a unidade de sentido de maior significÃncia para os informantes, designando um perÃodo diferente do que estÃo vivenciando atualmente e a necessidade de retornar suas atividades cotidianas e hÃbitos de vida relacionados à alimentaÃÃo, educaÃÃo, trabalho e lazer, resgatando assim sua autonomia e dignidade. O significado atribuÃdo ao transplante foi desvelado nÃo apenas como uma possibilidade de cura, mas a melhoria da qualidade de vida. Os pacientes revelaram o desejo de retribuir todo apoio recebido pela famÃlia durante esta fase crÃtica que vivenciam com a evoluÃÃo da doenÃa hepÃtica. A insuficiÃncia hepÃtica irreversÃvel à uma condiÃÃo patolÃgica de grande impacto na vida das pessoas, levando a necessidade de transplante de fÃgado como Ãnica possibilidade de reversÃo do quadro terminal, trazendo conseqÃÃncias diretas na qualidade de vida, com repercussÃes a nÃvel biolÃgico, psicolÃgico e social. As transformaÃÃes e limitaÃÃes impostas pela condiÃÃo crÃnica e pela necessidade de listagem para o transplante trazem a necessidade de adaptaÃÃo a uma nova realidade, tendo que se ajustarem as mudanÃas nos vÃrios campos da sua vida. Buscar o sentido e o significado que os pacientes atribuem à experiÃncia vivida no perÃodo prÃ-transplante à de suma importÃncia para o processo do cuidar, bem como conhecer suas histÃrias e experiÃncias vividas transcorridas em seu mundo, promovendo um ambiente assistencial mais humano.
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Clèries, Soler Ramon. "Geographic Variability in Liver Cancer." Doctoral thesis, Universitat Autònoma de Barcelona, 2006. http://hdl.handle.net/10803/4627.
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At the beginning of the 21st century, primary liver cancer (PLC) remains the fifth most common malignancy in men worldwide, and the eighth in women. Central Africa and South East of Asia are high risk geographic areas for PLC, whereas developed countries appear to be generally low risk. Infections with hepatitis B (HBV) and C (HCV) viruses are the main risk factors for PLC, accounting for well over 80% of PLC cases detected worldwide. The recently detected increase in both incidence and mortality by PLC in developed countries is strongly related to these viral infections. The evaluation of PLC time trends needs to take into consideration the geographic distribution and effect of these viruses. This thesis presents three studies which the aim to describe PLC incidence and mortality issues in different geographic areas, each addressing several epidemiological and methodological issues. For each study, different statistical methods on the basis of the Bayesian inference have been proposed, evaluated and discussed in order to cope with extra-Poisson variability. The first study, entitled "Meta-analysis of cohort studies of risk of liver cancer death among HBV carriers", evaluates the variability in PLC mortality reported in 11 cohort studies of male HBV carriers, taking into consideration the effects of geographic area and the choice of the general population versus a more comparable group such as HBV-negative workers or blood donors as the comparison group. The statistical methods of this study focuses on mixtures of Poisson distributions. The "stickbreaking" method has been used to estimate the number of components of the mixture of Poisson distributions, and, thus to obtain a pooled relative risk (RR) of death for PLC among male HBV carriers. The pooled RR of death by PLC related to HBV infection was 23.5 (95% Credibility Interval (CRI): 14.9 - 44.5). Studies carried out in high risk areas for PLC (China and Taiwan) showed RRs 2 to 5-fold higher than those of studies carried out in Europe, Japan and the U.S.. In low risk areas for PLC, studies which used workers or blood donors as comparison groups had RRs 1.9-fold higher (95% CRI: 1.2 - 3.1) than studies which used the general population. However, in high risk areas, the ratio of RRs was 5.3-fold (95% CRI: 3.4 - 7.9). This is the first time that a "healthy donor effect" has been quantified in longitudinal studies.
The second study, entitled "Geographic distribution of primary liver cancer in Europe in 2002" evaluates the effect of HBV and HCV seroprevalence in 38 European countries on PLC incidence and mortality. Mixed Poisson models based on Bayesian inference have been used to smooth Standardized Incidence (SIR) and Mortality (SMR) ratios for PLC accounting for the effect of HBV and HCV prevalences. This approach enabled us to both examine the effect of different levels of HBV and HCV, and to identify remaining variability in PLC after accounting for infection rates. Bayesian inference allowed the determination of posterior probabilities for the somoothed SIRs and SMRs (hereafter RRs). The Deviance Information Criterion (DIC) and the "effective number of parameters" (pD) have been used as tools for model choice. The highest mortality and incidence PLC RRs were found in Southern European countries (RR range 0.9-2.4), whereas Northern European countries showed the lowest RRs (RR range: 0.3-0.9). The effect of HBV infection was not found to be statistically significant in the model which accounted for both HBV and HCV prevalence. Countries with a prevalence of HCV higher than 2% (e.g.: Italy and Spain) had a higher risk of incidence and mortality (RR range: 1.28 - 1.78) than countries with HCV prevalence below 1%. Thus, the high risk of PLC detected in Southern Europe appears to be explained, in part, by HCV infection. The high HCV seroprevalence in this area could be associated with exposure 30-50 years ago. There may be an underestimation of PLC incidence and mortality rates in Eastern European countries given the low PLC RRs reported, despite high HBV and HCV seroprevalences observed. The implementation of population-based cancer registries in Eastern European countries is warranted, as well as HCV prevalence studies across Europe, to better determine the distribution of PLC in Europe and its relationship with that virus.
The last study, entitled "Time trends in liver disease in Spain during the period 198397", describes incidence and mortality trends in hepatocellular carcinoma and cholangiocarcinoma as well as mortality trends in liver cirrhosis in Spain. Autoregressive age-period-cohort (APC) models have been used to evaluate the time trends. We found that APC models performed well for those liver diseases with large number of cases, whereas the age-period models did for those liver diseases with low number of cases. We found an increase in incidence and mortality of hepatocellular carcinoma in Spain (annual percent change (APCH) in men's incidence: 6.6%, 95% CRI: 5.8, 8.1: APCH in women's incidence: 4.5%, 95% CRI: 1.4%, 7.3%; APCH in men's mortality: 6.8%, 95% CRI: 5.8%, 8.1%; APCH in women's mortality: 5.1%, 95% CRI: 3.5%, 6.3%), that appear to be related to HCV exposure 30 years ago, as described in other studies of PLC. We also found an increasing trend in cholangiocarcinoma mortality (APCH in men: 17.1%, 95% CRI: 13.5%, 21.2%; APCH in women: 15.0%, 95% CRI: 11.5%, 19.5%) similar to that found in some developed countries, that could be attributed to improvement in diagnosis resulting from better imaging and diagnostic techniques. However, we did not detect a significant increasing trend in cholangiocarcinoma incidence, perhaps due to the low number of cases reported by the Spanish cancer registries. We have observed a decreasing trend in cirrhosis mortality in both sexes during the study period (APCH in men: -3.1%, 95% CRI: -5.1, -1.9%; APCH in women: -2.9%; 95% CRI: -6.2%, -1.3%), although younger cohorts did not show this pattern. This cohort effect suggests the possibility that younger cohorts could be exposed to some additional risk factors besides alcohol consumption. HIV and HCV or HBV co-infection and intravenous drug addiction could explain the increase in liver cirrhosis mortality among younger cohorts.
The flexibility of the Bayesian approach allowed us to cope with extra-Poisson variability in three statistical analyses, applying different models, and addressing relevant methodological aspects specific to each problem. Challenging statistical issues in the framework of Bayesian applied modelling are: i) the selection of prior distributions for model parameters, which is related to convergence of the model; and ii) model selection procedures, and these remain important considerations for future research.
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Tacon, Geoffrey Reginald Russell. "Mathematical modelling of liver kinetics /." [St. Lucia, Qld.], 2005. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe19399.pdf.
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