Ischemic Cholangiopathy Research Articles

The bile duct in donation after cardiac death donor liver transplant.

This review considers the biliary complications associated with liver transplantation using donation after cardiac death (DCD) donor grafts. The increasing use of DCD liver grafts with their increased incidence of biliary complications is discussed. The ethics of this greater use is briefly analysed. Recent animal and human study evidence to support the peribiliary vascular plexus' role in ischaemic cholangiopathy is reviewed. Recent advances in in-vivo and ex-vivo perfusion are explored. In particular, the latest theories regarding perfusion's peribiliary plexus preserving effects and the mechanism by which biliary regeneration may be promoted as a consequence are discussed. This article explores the need for DCD liver graft use and the associated biliary complications. The current theories regarding the cause of DCD biliary complications are reviewed, as are the current strategies to reduce them.

Sanguineous normothermic machine perfusion improves hemodynamics and biliary epithelial regeneration in donation after cardiac death porcine livers.

The effects of normothermic machine perfusion (NMP) on the postreperfusion hemodynamics and extrahepatic biliary duct histology of donation after cardiac death (DCD) livers after transplantation have not been addressed thoroughly and represent the objective of this study. Ten livers (5 per group) with 60 minutes of warm ischemia were preserved via cold storage (CS) or sanguineous NMP for 10 hours, and then they were reperfused for 24 hours with whole blood in an isolated perfusion system to simulate transplantation. In our experiment, the arterial and portal vein flows were stable in the NMP group during the entire reperfusion simulation, whereas they decreased dramatically in the CS group after 16 hours of reperfusion (P < 0.05); these findings were consistent with severe parenchymal injury. Similarly, significant differences existed between the CS and NMP groups with respect to the release of hepatocellular enzymes, the volume of bile produced, and the levels of enzymes released into bile (P < 0.05). According to histology, CS livers presented with diffuse hepatocyte congestion, necrosis, intraparenchymal hemorrhaging, denudated biliary epithelium, and submucosal bile duct necrosis, whereas NMP livers showed very mild injury to the liver parenchyma and biliary architecture. Most importantly, Ki-67 staining in extrahepatic bile ducts showed biliary epithelial regeneration. In conclusion, our findings advance the knowledge of the postreperfusion events that characterize DCD livers and suggest NMP as a beneficial preservation modality that is able to improve biliary regeneration after a major ischemic event and may prevent the development of ischemic cholangiopathy in the setting of clinical transplantation.

Serum Alkaline Phosphatase and Bilirubin Are Early Surrogate Markers for Ischemic Cholangiopathy and Graft Failure After DCD Liver Transplantation.

Transplantation utilizing donation after circulatory death (DCD) donors is associated with ischemic cholangiopathy (IC) and graft loss. Early recognition and re-transplantation may offer the only chance for survival for patients with failing DCD liver grafts. We hypothesized that serial analysis of alkaline phosphatase and bilirubin might identify patients developing progressive ischemic cholangiopathy and at risk for graft loss. The University of Washington DCD experience totals 89 DCD liver transplants performed between 2003 and 2011 with Kaplan-Meier estimated 5 year patient and graft survival rates of 81.6% and 75.6% respectively. 85/89 patients transplanted with DCD livers lived at least 2 months post transplantation and were analyzed. Serum bilirubin and alkaline phosphatase levels at 1 week, 2 week, 1 month and 2 months post transplantation demonstrated that a 2 month alkaline phosphatase value >300 was highly predictive for development of ischemic biliary strictures (84.2%, p<0.001). Furthermore, 100% of jaundiced recipients at 2 months post transplantation (bilirubin >2.5) developed graft failure in the first year. (p<0.0001) Elevated alkaline phosphatase and bilirubin 2 months after transplantation is highly predictive of ischemic cholangiopathy and early graft failure after DCD liver transplantation. Utilization of these early surrogate markers could facilitate prioritization and early re-transplantation for recipients of failing DCD allografts.Figure: No Caption available.Figure: No Caption available.

Normothermic Machine Perfusion (NMP) Promotes Early Graft Function and Biliary Epithelial Regeneration After Transplantation of Porcine Livers Undergoing 1hr Warm Ischemia (WI).

Introduction: In this study we investigated the ability of ex-vivo NMP to prevent primary graft non function of severely injured DCD livers (WI=60 minutes) and to promote biliary epithelium regeneration. Methods: Four porcine livers exposed to 1hr WI were preserved by NMP for 7hrs with whole blood as perfusate, and then transplanted (DCD group). Two livers without WI were transplanted directly as a control group. Results: All 6 recipients presented with excellent early graft function, were extubated after surgery and presented normal kidney function. 2/4 DCD survived more than 5 days. 2/4 survived until POD 2 and were euthanized respectively for tacrolimus neurotoxicity and bowel obstruction. POD2 data are shown in Figure 1.Figure: No Caption available.Aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase of DCD livers presented lower peak values compared to the controls possibly. DCD livers presented with higher lactate peak which returned to normal after POD 1. Of most interest, all livers presented with intact liver parenchyma and extra-hepatic biliary architecture. Ki67 staining revealed regeneration of biliary epithelial cells of DCD livers suggesting active repair.Figure: No Caption available.Conclusion: Our data suggests that early graft function can be achieved in severely injured DCD preserved using NMP. Most importantly ex-vivo perfusion promotes biliary epithelial regeneration, a key factor involved in ischemic cholangiopathy.

Comparison of Short-Term and Long-Term Outcomes After DCD and DBD Donor Liver Transplantation.

Introduction: Liver transplantation (LT) using donation after cardiac death (DCD) allografts has been increased, however the occurrence of primary non-function (PNF) and ischaemic cholangiopathy (IC) has curbed their expansion. Here we compare the outcome of LT with donation after brain death (DBD) and DCD grafts performed in our institution. Study design: Between 2001-2013 we carried out 255 adult controlled DCD LT, which were compared to matched 255 DBD allografts. DCD grafts had a cut-off of maximum 30 min of warm ischaemia and were allocated to recipients with no previous extensive abdominal surgery. Results: There was no difference in gender and recipient's BMI between DBD and DCD transplants, however DBD donors were older and had longer cold ischaemic time. Patients that received DCD grafts presented higher levels of AST (p<0.0005), however, there was no significant difference in Intensive Care Unit or Hospital stay between the 2 groups. PNF was significantly higher in DCD allografts (p<0.0005); nevertheless, there was no statistically significant difference in the incidence of renal replacement therapy, rejection, biliary or vascular complications between the 2 groups. There were no significant differences in PIC occurrence between the 2 groups. Although more patients with hepatocellular carcinoma were allocated (64.06%) to a DCD graft, there was no difference in HCC recurrence. Overall patient and graft survival was higher in the DBD group (p =0.025, p=0.002). When transplants for HCC are excluded, no difference in overall patient and graft survival are observed. Conclusions: The data shows a favourable outcome of liver transplants using DCD allografts. More work is required to explore the impact of DCD status on HCC recurrence. Minimising CIT and optimising donor / recipient matching are crucial in order to achieve good outcome.

Risk Factors Predictive of Ischemic Cholangiopathy in Donation after Circulatory Death Liver Transplants Predict Recipient Morbidity: The 10 Year University of Colorado Experience.

Risk Factors Predictive of Ischemic Cholangiopathy in Donation after Circulatory Death Liver Transplants Predict Recipient Morbidity: The 10 Year University of Colorado Experience.

Etiology and management of hepatic artery thrombosis after adult liver transplantation

Hepatic artery thrombosis (HAT) represents a major cause of graft loss and mortality after liver transplantation. It occurs in up to 9% of adult recipients. The early diagnosis of HAT decreases septic complications, multiorgan failure, and graft loss, and there are better outcomes after treatment. In this study, we reviewed 102 episodes of HAT, which were classified as early hepatic artery thrombosis (E-HAT) when they were diagnosed within the first 21 days after transplantation. The overall incidence of HAT was 7%: 31 episodes (30.4%) were identified as E-HAT, and 71 episodes (69.6%) were identified as late hepatic artery thrombosis (L-HAT). Graft dysfunction was the commonest presentation (30 cases or 29%). Most E-HAT cases were managed with retransplantation (74%), whereas early revascularization was carried out for only 13% with a 75% success rate. The incidence of retransplantation for L-HAT was only 41%, whereas 32% were too ill for relisting and eventually died. Successful conservative management was noted for 13 of the 102 patients (13%) with collateralization and good hepatic perfusion, with biliary complications encountered in 7 cases (54%) subsequently. A multivariate analysis showed that previous episodes of HAT, the number of arterial anastomoses, and a low donor weight were independent risk factors for E-HAT, whereas a history of upper abdominal operations (non-HAT), a previous history of HAT, a low donor weight, and a recipient age < 50 years were independent risk factors for L-HAT. The graft survival rates for HAT patients were 52%, 36.6%, and 27.4% at 1, 3, and 5 years, whereas the corresponding rates were 81.4%, 81.2%, and 76.4% for non-HAT patients. In conclusion, prompt revascularization for E-HAT patients decreases the incidence of serious, irreversible septic complications and graft loss and improves overall outcomes. A significant number of L-HAT patients do not require further intervention despite the high incidence of ischemic cholangiopathy.

P894 PROPHYLAXIS OF DE NOVO HEPATITIS B VIRUS INFECTION WITH LAMIVUDINE IN HBsAg-NEGATIVE NAIVE RECIPIENTS OF HEPATITIS B CORE ANTIBODY-POSITIVE LIVERS: A 13-YEAR SINGLE-CENTER EXPERIENCE

Methods: • Patients: Consecutive outpatient LT recipients between January and December 2012 • Reference group G0: – >2-fold increase in liver function tests (LFT) or unexplained fibrosis >7kPa (Fibroscan) – Excluded: ischemic cholangiopathy, HBV, HVC, HVE post LT infections. • Control groups: – G1:primary LT, normal LFT – G2:primary LT, abnormal LFT – G3: HCV post-LT Patients were tested for donor specific antibodies (DSA) (Luminex SA), and the results expressed in MFI. Comparison of prevalence of DSA and MFI between G0 and control groups was made. Results: 91pts including 22 pts in G0 and 31, 19, 16 pts in G1, G2, G3 were investigated 9.6 yrs after LT. Fourteen (18.7%) pts had been re-transplanted. DSA were found in 95.5% in G0, anti class II in all cases, vs 50.9% in G1-G3 (p < 0.001). Prevalences of DSA in G1, G2 and G3 were 45.2, 52.6 and 68.8% (p =0.003), respectively. In pts with DSA, median MFI was 9916 in G0 vs 3443 in G0-G3 (p =0.02). Conclusions: Prevalence of DSA (95%) and MFI in G0 patients are significantly higher than in control groups. This highly suggests a role of AMR in long-term unexplained liver graft dysfunctions. In HCV positive pts, the prevalence of DSA was also found high and raises the issue of HCV as a contributor anti-HLA sensitization.

Aetiology and risk factors of ischaemic cholangiopathy after liver transplantation.

Liver transplantation (LT) is the best treatment for end-stage hepatic failure, with an excellent survival rates over the last decade. Biliary complications after LT pose a major challenge especially with the increasing number of procured organs after circulatory death. Ischaemic cholangiopathy (IC) is a set of disorders characterized by multiple diffuse strictures affecting the graft biliary system in the absence of hepatic artery thrombosis or stenosis. It commonly presents with cholestasis and cholangitis resulting in higher readmission rates, longer length of stay, repeated therapeutic interventions, and eventually re-transplantation with consequent effects on the patient's quality of life and increased health care costs. The pathogenesis of IC is unclear and exhibits a higher prevalence with prolonged ischaemia time, donation after circulatory death (DCD), rejection, and cytomegalovirus infection. The majority of IC occurs within 12 mo after LT. Prolonged warm ischaemic times predispose to a profound injury with a subsequently higher prevalence of IC. Biliary complications and IC rates are between 16% and 29% in DCD grafts compared to between 3% and 17% in donation after brain death (DBD) grafts. The majority of ischaemic biliary lesions occur within 30 d in DCD compared to 90 d in DBD grafts following transplantation. However, there are many other risk factors for IC that should be considered. The benefits of DCD in expanding the donor pool are hindered by the higher incidence of IC with increased rates of re-transplantation. Careful donor selection and procurement might help to optimize the utilization of DCD grafts.

Liver Transplantation in Children Using Organ Donation After Circulatory Death

While orthotopic liver transplantation (OLT) is a durable life-saving treatment for patients with irreversible liver disease, the waiting list mortality rate for children younger than 6 years is 4 times higher than for children aged 11 to 17 years and adults owing to scarce availability of size-appropriate grafts for transplantation. To compare long-term outcomes for children (aged ≤18 years) undergoing OLT using grafts from donation after circulatory death (DCD) and donation after brain death (DBD). Retrospective study using case-control matched groups at a university transplant center. All patients aged 18 years and younger who underwent OLT using DCD organs between February 1, 1990, and November 30, 2010, at the University of California, Los Angeles, were matched in a 1 to 3 ratio with patients who received primary OLT from DBD donors within a 12-month period. Other matching criteria included recipient age, weight, cause of liver disease, and acuity of illness. Outcomes after OLT were compared for DCD (n = 7) and DBD (n = 21) donors. The median follow-up was 4.5 years. The primary outcome measure was graft failure-free survival; the secondary end point was the development of ischemic cholangiopathy. Comparing DCD and DBD groups, recipient median age (28.4 vs 20.1 months, respectively; P = .80), weight (12.0 vs 11.6 kg, respectively; P = .87), Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease score (19 vs 11, respectively; P = .48), and donor age (24.0 vs 13.1 months, respectively; P = .72) were similar. For the DCD donors, the median donor warm ischemia duration was 24 minutes. Liver test results were similar for both groups at 1 week and 3, 6, and 12 months following OLT. Ten-year patient and graft survival rates for both DCD and DBD were 100%. Neither ischemic cholangiopathy nor vascular complications occurred in the DCD group. Biliary anastomotic strictures occurred in 1 DCD patient and 3 DBD patients. Our study showed excellent long-term outcomes with liver transplantation in children using DCD organs. Use of liver grafts procured after circulatory death is an effective approach to expand the donor pool and remains an untapped resource for children with end-stage liver disease.

Regional perfusion by extracorporeal membrane oxygenation of abdominal organs from donors after circulatory death: A systematic review

Organs from donors after circulatory death (DCDs) are particularly susceptible to the effects of warm ischemia injury. Regional perfusion (RP) by extracorporeal membrane oxygenation (ECMO) is increasingly being advocated as a useful remedy to the effects of ischemia/reperfusion injury, and it has been reported to enable the transplantation of organs from donors previously deemed unsuitable. The MEDLINE, Embase, and Cochrane databases were searched, and articles published between 1997 and 2013 were obtained. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Two hundred ten articles were identified, and 11 were eligible for inclusion. Four hundred eighty-two kidneys and 79 livers were transplanted from regional perfusion-supported donor after circulatory death (RP-DCD) sources. One-year graft survival was lower with uncontrolled RP-DCD liver transplantation, whereas 1-year patient survival was similar. Primary nonfunction and ischemic cholangiopathy were significantly more frequent with RP-DCDs versus donors after brain death (DBDs), but there was no difference in postoperative mortality between the 2 groups. The 1-year patient and graft survival rates for RP-DCD kidney transplantation were better than the rates with standard DCDs and were comparable to, if not better than, the rates with DBDs. At experienced centers, delayed graft function (DGF) for kidney transplantation from RP-DCDs was much less frequent in comparison with all other donor types. In conclusion, RP aids the recovery of DCD organs from ischemic injury and enables transplantation with acceptable survival. RP may help to increase the donor pool, but its benefits must still be balanced with the recognition of significantly higher rates of complications in liver transplantation. In kidney transplantation, significant reductions in DGF can be obtained with RP, and there are potentially important implications for long-term outcomes. Significant ethicolegal issues exist, and they are preventing a worldwide consensus on optimum RP protocols and an accurate appreciation of outcomes.

Left Accessory Hepatic Artery Damage by a Misplaced Gastric Band in a Deceased Liver Donor

During a multiorgan procurement, we noticed that a gastric band was ectopically placed around the hepatogastric ligament and the left accessory hepatic artery (LaHA) instead of being placed just below the gastroesophageal junction (Fig. 1A–D). The donor body mass index was 38.7 and had a history of gastric banding 2 years before without significant weight loss. The left accessory artery was identified during warm dissection and was found to arise from the left gastric artery. It had a diameter of 3 mm (Fig. 1B and 1D). The pulse was strong and there was no evidence of atrophy of the left lobe, and it was kept intact. However, at the back-table dissection, it was noted that the band had been sutured on the arterial wall of the LaHA, and there was diffuse scarring of the surrounding tissue (Fig. 1A). We decided to ligate the LaHA after confirming it was an accessory hepatic artery and not a left replaced hepatic artery. The liver had 10% macrosteatosis and the cold ischemia time was 7 hr and 31 min. Our recipient was a 50 year old, with hepatitis C virus and hepatocellular carcinoma, Model for End-stage Liver Disease 31. The peak of aspartate aminotransferase and alanine aminotransferase (on postoperative day 1) was 1319 and 544 mg/dL, respectively. The patient had an uneventful postoperative course, and now 4 months after the transplantation, he is doing well, with normal liver function tests.FIGURE 1: Gastric band was found to be around the hepatogastric ligament (A) instead of being around the gastroesophageal junction (B). There was severe scarring of the hepatogastric duodenal ligament. The LaHA was compressed by the balloon and stitched to the band. LGA, left gastric artery. C, liver graft before the back-table hilar dissection. The gastric band is found around the hepatogastric duodenal ligament. D, Liver graft after the back table dissection. The left accessory vein is visualized inside the gastric band. Ao, aorta; cHA, common hepatic artery; HGDL, hepatogastric duodenal ligament; LL, left lobe; PV, portal vein; RL, right lobe; SA, splenic artery.Laparoscopic adjustable gastric banding is considered to be a safe and effective method of weight loss. The incidence of complications is extremely low (1). This is, to our knowledge, the first report a gastric band has been placed around the hepatogastric ligament (including the accessory left hepatic artery) instead of the stomach. When present, LaHA originates from the left gastric artery and runs through the pars condensa of the lesser omentum. Its frequency varies from 12% to 34% according to the different study methods: 14% to 27% in anatomical series, 12% to 20% in angiographic studies, 12% to 24% in liver transplantation series, and during laparoscopic operations in 18% to 34% of cases. LaHA supplies a variable liver area ranging from a part of the left lobe to the whole liver in less than 1% of cases. Standard surgical teaching is to attempt reconstruction of an injured LaHA to avoid biliary complications, such as ischemic cholangiopathy. However, due to potential preexisting anastomosis or later collateralization between liver arteries, LaHA ligation is tolerated in most cases with only a transitory elevation of liver enzymes (2–5). In a series of 720 laparoscopic hiatal antireflux procedures, 57 (7.9%) patients had the LaHA divided. None of the patients with divided hepatic arteries had postoperative symptoms related to impaired liver function. Postoperatively, only 2 (11.7%) patients had transient elevated liver enzymes. At a mean follow-up of 28.5±12.8 months, no specific complaints could be identified (6). In our case, before ligating the artery, we first checked if this artery was an accessory and not a replaced artery; second, we visualized back-bleeding into this artery after reperfusion, which may represent a sign of collateral/redundant arterial supply. The postoperative course was uneventful. The dissection of the hepatoduodenogastric ligament in donors with previous operations and adhesions/scarring of this area should be carefully performed to prevent damage to a potential LaHA. In addition, dissection of this area in donation after cardiac death donors should be carried out with extra care because pulsation of this artery cannot be assessed in advance and can be easily mistaken for a nerve of vein. Paulo Ney Aguiar Martins James McDaid James F. Markmann Transplant Division Department of Surgery Massachusetts General Hospital Harvard University Boston, MA

Long-term deleterious effects of aortohepatic conduits in primary liver transplantation: Proceed with caution

Aortohepatic conduits provide a vital alternative for graft arterialization during liver transplantation. Conflicting results exist with respect to the rates of comorbidities, and long-term survival data on primary grafts are lacking. To identify the complications associated with aortohepatic conduits in primary liver transplantation and their impact on survival, we conducted a single-center, retrospective cohort analysis of all consecutive adult (n = 1379) and pediatric primary liver transplants (n = 188) from 1998 to 2009. The outcomes of aortohepatic conduits were compared to those of standard arterial revascularization. Adults with a conduit (n = 267) demonstrated, in comparison with adults with standard arterialization (n = 1112), an increased incidence of late (>1 month after transplantation) hepatic artery thrombosis (HAT; 4.1% versus 0.7%, P < 0.001) and ischemic cholangiopathy (7.5% versus 2.7%, P < 0.001) and a lower 5-year graft survival rate (61% versus 70%, P = 0.01). The adjusted hazard ratio (HR) for graft loss in the conduit group was 1.38 [95% confidence interval (CI) = 1.03-1.85, P = 0.03]. Notably, the use of conduits (HR = 4.91, 95% CI = 1.92-12.58) and a warm ischemia time > 60 minutes (HR = 11.12, 95% CI = 3.06-40.45) were independent risk factors for late HAT. Among children, the complication profiles were similar for the conduit group (n = 81) and the standard group (n = 107). In the pediatric cohort, although the 5-year graft survival rate for the conduit group (69%) was significantly impaired in comparison with the rate for the standard group (81%, P = 0.03), the use of aortohepatic conduits did not emerge as an independent predictor of diminished graft survival via a multivariate analysis. In conclusion, in adult primary liver transplantation, the placement of an aortohepatic conduit should be strictly limited because of the greater complication rates (notably late HAT) and impaired graft survival; for children, its judicious use may be acceptable.

Unrelated allogeneic bone marrow-derived mesenchymal stem cells for steroid-refractory acute graft-versus-host disease: a phase I/II study

We conducted a multicenter phase I/II study using mesenchymal stem cells (MSCs) manufactured from the bone marrow of healthy unrelated volunteers to treat steroid-refractory acute graft-versus-host disease (aGVHD). Fourteen patients with hematological malignancies who suffered from grade II (9 patients) or III aGVHD (5) were treated. Affected organs were gut (10 patients), skin (9 patients), and liver (3 patients). Seven patients had two involved organs. The median age was 52. No other second-line agents were given. MSCs were given at a dose of 2×10(6) cells/kg for each infusion twice a week for 4weeks. If needed, patients were continuously given MSCs weekly for an additional 4weeks. By week 4, 13 of 14 patients (92.9%) had responded to MSC therapy with a complete response (CR; n=8) or partial response (PR; n=5). At 24weeks, 11 patients (10 with CR and 1 with PR) were alive. At 96weeks, 8 patients were alive in CR. A total of 6 patients died, attributable to the following: underlying disease relapse (2 patients), breast cancer relapse (1), veno-occlusive disease (1), ischemic cholangiopathy (1), and pneumonia (1). No clear adverse effects associated with MSC infusion were observed. Third party-derived bone marrow MSCs may be safe and effective for patients with steroid-refractory aGVHD.

Retransplantation of the Liver: Review of Current Literature for Decision Making and Technical Considerations

Liver transplantation (LTx) is an established treatment modality for patients with end-stage liver disease, metabolic disorders, and patients with acute liver failure. When a graft fails after primary LTx, retransplantation of the liver (reLTx) is the only potential cure. ReLTx accounts for 7%–10% of all LTx in the United States. Early causes of graft failure for which reLTx may be indicated include primary graft nonfunction and vascular inflow thrombosis. ReLTx in such cases in the early postoperative period is usually straightforward as long as an appropriate secondary allograft is secured in a timely fashion. Late indications may include ischemic cholangiopathy, chronic rejection, and recurrence of the primary liver disease. ReLTx performed in the late period is often more complex and selection criteria are more stringent due to the persistent shortage of organs. The question of whether to retransplant patients with recurrent hepatitis C remains controversial, but these practices are likely to change as the epidemic progresses and new treatments evolve. We also present recent results with reLTx from Yale–New Haven Transplant Center and early results with the use of living donors for reLTx.

Cholangiopathie ischémique secondaire à des brûlures étendues

Ischemic cholangiopathy is a recently described entity occurring mainly after hepatic grafts. Very few cases after intensive care unit (ICU) for extended burn injury were reported. We report the case of a 73-year-old woman consulting in an hepatology unit, for a jaundice appearing during a hospitalisation in an intensive care unit and increasing from her leaving from ICU, where she was treated for an extended burn injury. She had no pre-existing biological features of biliary disease. Biological tests were normal. Magnetic resonance imaging acquisitions of biliary tracts pointed out severe stenosing lesions of diffuse cholangiopathy concerning intrahepatic biliary tract, mainly peri-hilar. Biopsie from the liver confirmed the diagnosis, showing a biliary cirrhosis with bile infarcts. This case is the fourth case of ischemic cholangiopathy after extended burn injury, concerning a patient without a prior history of hepatic or biliary illness and appearing after hospitalisation in intensive care unit.

Is liver transplantation using organs donated after cardiac death cost‐effective or does it decrease waitlist death by increasing recipient death?

ObjectivesThe aim of this study was to evaluate the cost‐effectiveness in liver transplantation (LT) of utilizing organs donated after cardiac death (DCD) compared with organs donated after brain death (DBD). MethodsA Markov‐based decision analytic model was created to compare two LT waitlist strategies distinguished by organ type: (i) DBD organs only, and (ii) DBD and DCD organs. The model simulated outcomes for patients over 10 years with annual cycles through one of four health states: survival; ischaemic cholangiopathy; retransplantation, and death. Baseline values and ranges were determined from an extensive literature review. Sensitivity analyses tested model strength and parameter variability. ResultsOverall survival is decreased, and biliary complications and retransplantation are increased in recipients of DCD livers. Recipients of DBD livers gained 5.6 quality‐adjusted life years (QALYs) at a cost of US$69 000/QALY, whereas recipients on the DBD + DCD LT waitlist gained 6.0 QALYs at a cost of US$61 000/QALY. The DBD + DCD organ strategy was superior to the DBD organ‐only strategy. conclusionsThe extension of life and quality of life provided by DCD LT to patients on the waiting list who might otherwise not receive a liver transplant makes the continued use of DCD livers cost‐effective.

Improvement of ischemic cholangiopathy in three patients with hereditary hemorrhagic telangiectasia following treatment with bevacizumab

The ischemic biliary phenotype of hereditary hemorrhagic telangiectasia (HHT) is rare but distinct, with progressive biliary tree ischemia usually resulting in an irreversible secondary sclerosing cholangiopathy. When clinically severe, liver transplant is often indicated. We report three patients with marked HHT associated biliary disease, in whom prolonged anti-vascular endothelial growth factor therapy (bevacizumab) notably reversed imaging evidence of biliary disease and clinically obviated need for liver transplantation during the first year of follow-up.

Long-term management of the successful adult liver transplant: 2012 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation

Michael R. Lucey, Norah Terrault, Lolu Ojo, J. Eileen Hay, James Neuberger, Emily Blumberg, and Lewis W. Teperman Division of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI; Gastroenterology Division, Department of Medicine, University of California San Francisco, San Francisco, CA; Division of Nephrology, Department of Medicine, University of Michigan, Ann Arbor, MI; Mayo Clinic, Rochester, MN; Liver Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom; Division of Infectious Diseases, University of Pennsylvania School of Medicine, Philadelphia, PA; and Department of Surgery, NYU Transplant Associates, New York, NY

Successful Treatment of Ischemic Cholangiopathy in Maastricht Type II Donors after Cardiac Death (DCD) Liver Recipients

Introduction: The increased number of patients in the waiting list and the donor shortage leads us to consider alternative sources of organs for our liver transplant candidates. One of these organ sources are donors from cardiac death (DCD). An increased incidence of ischemic cholangiopathy (IC) has been reported when these grafts are transplanted on. This complication could lead to severe graft dysfunction or even graft loss. The aim of our study is to analyze the patient and graft outcomes whenever ischemic cholangiopathy is diagnosed and what available treatment options we can offer these patients. Methods: From January 2006 to December 2010, 289 OLT were performed at our hospital. 44 of them (15.2%) were from DCD Maastrich tipe II. The most common cause of end stage liver disease was Hepatitis C, alone or associated with alcohol abuse and/or hepatocellular carcinoma. We defined ischemic cholangiopathy in patients who developed nonanastomotic strictures and dilatations involving the hepatic confluence or the intrahepatic biliary tree, in the absence of arterial thrombosis. The diagnosis was performed on the basis of radiological tests. Liver biopsy was performed in order to confirm it, when necessary. Thus, 14 patients (31.81%) were diagnosed of ischemic cholangiopathy. The average time between transplantation and diagnosis was 6.15 months (± 4.49). Results: The average age of the recipients and donors were 59.14 (± 8.2) and 40.43 (±10.1) years, respectively. 71.4% of our recipients were male. The average MELD value was 14 (± 3.4). Fourteen patients of 44 transplanted with DCD (31.81%) developed IC. Two of these patients (14.28%) did not require any treatment since no symptom or laboratory test deranging was observed, and other 2 patients (14.28%) required retransplant because of sever graft dysfunction. On the other hand most of these patients (12 recipients, 85.7% of those who were found to suffer IC) required radiological treatment by transparietohepatic cholangiography. Seven of the 14 patients (50%) with IC experienced resolution of the biliary complication at the moment, after an average number of procedures performed of 4.75 (± 4.1). We cannot consider cured 4 of the seven patients which have not experienced radiological resolution yet (28.5%) although a minimal impact on graft function has been observed in these cases. The other 3 patients (21.5%) have died (two of them because of HCV recurrence). The overall recipient and graft survival with IC was at 1, 3 and 5 years of follow up was 85.7%, 78.57%, 71.42%, and 85.7%, 64.28%, 57.14%, respectively. Conclusions: The most important complication in DCD transplant is ischemic cholangiopathy. However, a great number of our patients with ischemic cholangiopathy experiments good outcomes with radiologic treatment and even get cured. Not all the patients with ischemic cholangiopathy require retransplant or treatment, but a good multidisciplinary management may be the best solution of this problem in a great percentage of cases.