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Biliary complications in liver transplantation: role of the hepatic ischaemia-reperfusion injury
Full text linkIntroduction
Liver transplantation is currently the only effective therapy for patients with end stage acute or chronic liver failure. The increasing request of organs has led to the more extensive use of the so-called marginal donors, in particular donors after circulatory death (DCD).
Within this model of donation, a more severe degree of ischaemia-reperfusion injury (IRI) is occurring, that seems to play a role on the pathogenesis of local and remote organ complications.
This research will focus on the influence of liver graft injury on the pathogenesis of local and remote organ complications, evidencing the role of IRI leading to biliary complications and development of systemic inflammatory response associated with the occurrence of acute kidney injury (AKI).
Aim of the study was to assess the role of IRI in two different models of ischaemia, DCD and donation after brain death (DBD), in liver transplanted grafts, on the pathogenesis of local and remote organ complications.
We evaluated the development of biliary complications and its association with the degree of donor liver graft bile duct injury after liver reperfusion.
Moreover, the development of AKI after liver transplantation was considered, as consequence of IRI and systemic inflammatory response.
Methods
Retrospective single-centre study of adult patients who underwent liver transplantation at University Hospital Birmingham (UHB) National Health Service (NHS) Foundation Trust from January 2007 to December 2014.
Characteristics of recipient at transplant, recipient renal and liver function in the immediate pre-transplant period, donor and graft variables, intra-operative parameters, indicators of initial graft function and renal function in the post-transplant period were considered.
Primary end points were the occurrence of biliary complications, in particular ischaemic cholangiopathy (IC), and development of AKI. Secondary end point was the evaluation of IRI damage on the basis of transaminases, bilirubin and INR over the first week post-transplant and the appearance of bile duct retrieved after liver reperfusion on histological examination.
Severity of donor bile duct injury was assessed and scored on the basis of biliary epithelial cell loss, mural stroma necrosis, inflammation, peribiliary vascular plexus (PVP) damage, arteriolonecrosis, thrombosis, periluminal and deep peribiliary glands (PBGs) damage.
Cholangiocyte apoptosis in periluminal and deep PBGs was evaluated by quantitative terminal deoxy-nucleotidyl transferase dUTP-mediated nick-end labeling (TUNEL) analysis on bile duct sections. Cholangiocyte proliferation was studied in bile duct sections by PCNA immunohistochemical expression.
Results
One thousand and 60 liver transplant recipients (813 from DBD and 247 from DCD) were considered.
Recipients from DCD had higher ALT and AST in the first 7 days after transplant, compared to DBD. The occurrence of biliary complications was higher in DCD liver transplant recipients (85/247; 34%) compared to DBD (166/813; 20%) (p<0.001), in particular IC incidence was significantly higher in DCD.
The incidence of AKI was 59.3% (629/1060 recipients) and was significantly higher in DCD (160/247, 64.8%) compared to DBD (469/813, 57.7%) recipients (p=0.047).
Sixty-two patients comparable with the entire cohort, had the bile duct sample available for histological evaluation. A significantly higher number of DCD patients presented necrosis >50% of the bile duct wall [DCD 14/28 (50%), DBD 9/34 (26.5%) p=0.056], PVP damage [DCD 8/28 (29%), DBD 3/34 (9%); p=0.053] and periluminal PBGs damage [DCD 20/28 (71%), DBD 14/34 (41%); p=0.016]. These features defined the occurrence of severe histological injury, that was significantly more frequent in DCD liver transplant patients [15/28 (53.6%)] compared to DBD [7/34 (20.6%)] (p=0.007). A significant increased apoptosis and decreased proliferation was evidenced in both periluminal (Tunel assay p=0.029; PCNA expression p=0.029) and deep PBGs (Tunel assay p=0.002; PCNA expression p=0.006) from bile duct sample with severe histological injury.
Discussion
A more severe degree of IRI is occurring within DCD, as evidenced by greater graft dysfunction and increasing peak perioperative transaminases, likely related to the added donor warm ischaemia time.
The IRI seems to play a role on the pathogenesis of local and remote organ complications, evidencing the role exerted in DCD leading to biliary complications and development of systemic inflammatory response associated with the occurrence of AKI.
This study also shows an early picture of microscopic damage at the level of the bile duct soon after reperfusion of liver graft during transplantation. Bile duct samples retrieved from DCD grafts expressed more severe injury at the histological level, as evidenced by the increased incidence of mural stroma necrosis, PBP damage and PBG damage, defining the new feature of severe histological injury.
Bile ducts with severe histological injury showed increased apoptosis and reduced proliferation, as evaluated by Tunel assay and PCNA expression, both on periluminal and deep PBG cholangiocytes.
The higher incidence of IC development in DCD strongly suggests a relation between the occurrence of severe histological injury and alteration in bile duct repair mechanisms, raising hypothesis to further evaluate those mechanisms leading to the development of bile duct non-anastomotic strictures
Signalling Language Choice in Anglo-Saxon and Frankish Charters, c.700–c.900
Full text linkThough Germanic vernaculars enjoyed different statuses in relation to Latin in England and on the continent, authors of documents in both regions made specific choices concerning their use of language. This chapter explores how these linguistic decisions were sometimes signalled and what they imply through a comparative study of self-conscious language-use in Anglo-Saxon and Frankish legal documents, including both royal diplomas and ‘private’ (i.e. non-royal) charters, between c.700 and c.900. The enquiry focuses on significant cases of code-switching between Latin and Germanic vernacular. We identify and compare how charter scribes signalled a switch in language, as for instance in documents where Latin prose is interrupted with a qualifying phrase to describe something in a Germanic language. In addition, we examine instances of specific linguistic awareness in charters, including explicit references to the theodisca (usually continental Germanic language) and saxonica (usually Old English) languages.
These code switches and identifications of language reveal an acute linguistic consciousness on the part of the draftsmen and offer an opportunity for direct comparison between two cultures whose diplomatic practices have often seemed to be markedly different. In both regions the most frequent use of Germanic vernacular in charters came in descriptions of land and boundaries (though in England, Old English could also be employed for other purposes and in different sections of a charter). While acknowledging the pragmatism of transmitting certain pieces of information in the vernacular, we argue that the use of the vernacular in descriptions of landscape and property was often also an assertion of territoriality and a meaningful representation of identity. The status of Latin as the standard language of written communication in both regions has hitherto tended to lead scholars to suppose that Germanic insertions and qualifying phrases were included in charters purely to facilitate communication in societies with relatively low Latin literacy. Our study, by contrast, shows that the vernacular could be invoked quite deliberately, that it could be exploited as a means of engendering social inclusion or exclusion, and that it ultimately conveyed intentions and meanings which went far beyond simple clarification
Itinerari del destino. Incontri con il Codice Cospi
No full textIl testo illustra la storia dell'incontro tra l'autore e il Codice Cospi, manoscritto mesoamericano precoloniale conservato presso la Biblioteca Universitaria di Bologn
Liver transplantation: role of immunosuppression, renal dysfunction and cardiovascular risk factors
No full textIn the past decades, advances in immunosuppression, organ preservation, surgical techniques and better management of post-transplantation complications have led to improvement in survival of liver transplant patients. Such extended survival of liver graft recipients in their fifties and sixties has resulted in a greater prevalence of complications, in particular chronic kidney (CKD) and cardiovascular diseases (CVD). Renal failure and cardiovascular complications in the setting of liver transplantation are associated to an increase of morbidity and mortality. A 4-fold increased risk of death is reported among patients developing post-transplant CKD, and CVD is the leading cause of death with a functioning allograft, accounting for as much as 30% of post-transplant mortality. The onset is multifactorial, with pre-transplant conditions involved, including pre-transplant renal insufficiency, hepatitis C virus infection and pretransplant diabetes. Acute renal dysfunction in the setting of transplantation is also responsible of post-transplant CKD. Immunosuppressive therapy is primarily responsible for the development of CKD. Metabolic syndrome and its individual components, including diabetes mellitus, systemic hypertension, dyslipidemia, and obesity, are increasingly being identified as closely related to immunosuppressive therapy and actively contribute to cardiovascular morbidity and mortality in transplant patients. Treatment of modifiable risk factors is mandatory aiming to prevent the development and progression of serious complications. Early recognition, prevention and treatment of these conditions may further improve long-term survival after liver transplantation
Sapienza ovvero l’arte di andare oltre
No full textNell'ambito di questa raccolta di "dichiarazioni d'amore" per i libri, scaturita dall'esperienza pluriennale del seminario "Ex Libris" presso la Biblioteca di Discipline Umanistiche di Bologna, in collaborazione con l'Alma Mater, ogni contributore è stato chiamato a svelare un tassello librario per lui importante, caro, significativo per la propria vita, carriera, esperienza personale. Il mio pezzo ricorda la figura di Modesta, affascinante e contraddittoria protagonista del coraggioso romanzo "L'arte della gioia" di Goliarda Sapienza
Irnerio e il suo maestro in faccia all'oceano
No full textRoberto di Torigni è credibile, nella sua Cronaca, quando indica Lanfranco da Pavia maestro di Irnerio in Normandi
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