Steatosis of the Graft Is a Risk Factor for Posttransplantation Biliary Complications

Baccarani, Umberto; Adani, Gian Luigi; Isola, Miriam; Avellini, Claudio; Lorenzin, Dario; Rossetto, Anna; Currò, Giuseppe; Comuzzi, C.; Toniutto, Pierluigi; Soldano, Franca; Bresàdola, Vittorio; Risaliti, Andrea; Bresadola, F

doi:10.1016/j.transproceed.2009.03.084

Cited by 29 publications

(19 citation statements)

References 8 publications

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“…This was manifested by higher aminotransferases and poor bile production after transplant and equated with excess 3‐month mortality and allograft loss. In the era where the 60‐ to 70‐year‐old organ is not uncommon and where significant donor steatosis is frequent, perhaps one of the consequences is biliary ischemia and hence stricture formation from problems with the biliary microcirculation, as a recent study has suggested 47…”

Section: Discussionmentioning

confidence: 99%

Posttransplant biliary complications in the pre- and post-model for end-stage liver disease era

et al. 2011

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Section: Discussionmentioning

confidence: 99%

Posttransplant biliary complications in the pre- and post-model for end-stage liver disease era

et al. 2011

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“…This increases the WIT of the arterially perfused bile ducts. Simultaneous arterial and portal reperfusion reduced the biliary ischemic time and subsequently also NAS (58,73). However, others failed to prove this correlation (74).…”

Section: Prophylaxis Of Nasmentioning

confidence: 99%

Biliary Complications After Liver Transplantation: Old Problems and New Challenges

Seehofer

Eurich

Veltzke‐Schlieker

et al. 2013

American Journal of Transplantation

252

233

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Due to a vulnerable blood supply of the bile ducts, biliary complications are a major source of morbidity after liver transplantation (LT). Manifestation is either seen at the anastomotic region or at multiple locations of the donor biliary system, termed as nonanastomotic biliary strictures. Major risk factors include old donor age, marginal grafts and prolonged ischemia time. Moreover, partial LT or living donor liver transplantation (LDLT) and donation after cardiac death (DCD) bear a markedly higher risk of biliary complications. Especially accumulation of several risk factors is critical and should be avoided. Prophylaxis is still a major issue; however no gold standard is established so far, since many risk factors cannot be influenced directly. The diagnostic workup is mostly started with noninvasive imaging studies namely MRI and MRCP, but direct cholangiography still remains the gold standard. Especially nonanastomotic strictures require a multidisciplinary treatment approach. The primary management of anastomotic strictures is mainly interventional. However, surgical revision is finally indicated in a significant number of cases. Using adequate treatment algorithms, a very high success rate can be achieved in anastomotic complications, but in nonanastomotic strictures a relevant number of graft failures are still inevitable.

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“…3–7 A further effect of steatosis is the development of post-transplant ischemic-type biliary lesions. 8 Even for normal organs the biliary tree is known as the Achille's heel of OLT. 9–13 The formation of bile depends on the structural and functional integrity of the biliary tree and its impairment results in cholestasis.…”

Section: Introductionmentioning

confidence: 99%

“…18 A single study has related the degree of steatosis to the risk of post-transplantation biliary complications, suggesting that the impaired sinusoidal microcirculation could be responsible of the ischemic damage to the biliary tree. 8 To the best of our knowledge, no study addressed the role of the various compartments of the biliary tree of FLs in the altered production of bile. An adequate histochemical marker is thus necessary to monitoring the functionality and possible alterations of the biliary tree of FL induced by OLT.…”

Section: Introductionmentioning

confidence: 99%

Dipeptidylpeptidase-IV, a key enzyme for the degradation of incretins and neuropeptides: activity and expression in the liver of lean and obese rats

et al. 2012

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Given the scarcity of donors, moderately fatty livers (FLs) are currently being considered as possible grafts for orthotopic liver transplantation (OLT), notwithstanding their poor tolerance to conventional cold preservation. The behaviour of parenchymal and sinusoidal liver cells during transplantation is being studied worldwide. Much less attention has been paid to the biliary tree, although this is considered the Achille's heel even of normal liver transplantation. To evaluate the response of the biliary compartment of FLs to the various phases of OLT reliable markers are necessary. Previously we demonstrated that Alkaline Phosphatase was scarcely active in bile canaliculi of FLs and thus ruled it out as a marker. As an alternative, dipeptidylpeptidase-IV (DPP-IV), was investigated. This ecto-peptidase plays an important role in glucose metabolism, rapidly inactivating insulin secreting hormones (incretins) that are important regulators of glucose metabolism. DPP-IV inhibitors are indeed used to treat Type II diabetes. Neuropeptides regulating bile transport and composition are further important substrates of DPP-IV in the enterohepatic axis. DPP-IV activity was investigated with an azo-coupling method in the liver of fatty Zucker rats (fa/fa), using as controls lean Zucker (fa/+) and normal Wistar rats. Protein expression was studied by immunofluorescence with the monoclonal antibody (clone 5E8). In Wistar rat liver, DPP-IV activity and expression were high in the whole biliary tree, and moderate in sinusoid endothelial cells, in agreement with the literature. Main substrates of DPP-IV in hepatocytes and cholangiocytes could be incretins GLP-1 and GIP, and neuropeptides such as vasoactive intestinal peptide (VIP) and substance P, suggesting that these substances are inactivated or modified through the biliary route. In lean Zucker rat liver the enzyme reaction and protein expression patterns were similar to those of Wistar rat. In obese rat liver the patterns of DPP-IV activity and expression in hepatocytes reflected the morphological alterations induced by steatosis as lipid-rich hepatocytes had scarce activity, located either in deformed bile canaliculi or in the sinusoidal and lateral domains of the plasma membrane. These findings suggest that bile canaliculi in steatotic cells have an impaired capacity to inactivate incretins and neuropeptides. Incretin and/or neuropeptide deregulation is indeed thought to play important roles in obesity and insulin-resistance. No alteration in enzyme activity and expression was found in the upper segments of the biliary tree of obese respect to lean Zucker and Wistar rats. In conclusion, this research demonstrates that DPP-IV is a promising in situ marker of biliary functionality not only of normal but also of fatty rats. The approach, initially devised to investigate the behaviour of the liver during the various phases of transplantation, appears to have a much higher potentiality as it could be further exploited to investigate any pathological or stressful conditions i...

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Steatosis of the Graft Is a Risk Factor for Posttransplantation Biliary Complications

Cited by 29 publications

References 8 publications

Posttransplant biliary complications in the pre- and post-model for end-stage liver disease era

Posttransplant biliary complications in the pre- and post-model for end-stage liver disease era

Biliary Complications After Liver Transplantation: Old Problems and New Challenges

Dipeptidylpeptidase-IV, a key enzyme for the degradation of incretins and neuropeptides: activity and expression in the liver of lean and obese rats

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Steatosis of the Graft Is a Risk Factor for Posttransplantation Biliary Complications

Cited by 29 publications

References 8 publications

Posttransplant biliary complications in the pre- and post-model for end-stage liver disease era

Posttransplant biliary complications in the pre- and post-model for end-stage liver disease era

Biliary Complications After Liver Transplantation: Old Problems and New Challenges

Dipeptidylpeptidase-­IV, a key enzyme for the degradation of incretins and neuropeptides: activity and expression in the liver of lean and obese rats

Contact Info

Product

Resources

About

Dipeptidylpeptidase-IV, a key enzyme for the degradation of incretins and neuropeptides: activity and expression in the liver of lean and obese rats