Incidence Of Nonanastomotic Biliary Strictures Research Articles

Normothermic regional perfusion in controlled DCD liver procurement: Outcomes of the Swedish national implementation protocol.

Liver transplantation (LTX) using donors after controlled circulatory death (cDCD) is associated with poorer graft survival and increased incidence of nonanastomotic biliary strictures (NASs) compared to livers procured from brain-dead donors (DBD). The use of normothermic regional perfusion (NRP) during cDCD procurement may improve posttransplant outcomes and reduce the incidence of NAS. In Sweden, cDCD LTX was introduced through a national pilot protocol with mandatory NRP. This study aims to evaluate the outcome of cDCD LTX during the pilot period. Donor and recipient data were collected on all cDCD liver transplants during the pilot period between January 2020 to December 2022. Outcome on NAS, patient and graft survival, early allograft dysfunction, acute kidney injury, and comprehensive complication index was compared to a matched cohort of 28 patients transplanted with a DBD liver between 2018 and 2022. Eighteen patients were transplanted with a liver from a cDCD donor after using NRP. The mean functional warm ischemia time was 29 ± 6 minutes. The mean lactate reduction during NRP was 8.7 ± 2.4mmol/L, and the end NRP perfusate alanine aminotransferase was 1.4 ± 1µkat/L. When comparing recipients of cDCD liver transplant to DBD, no significant differences were observed in the incidence of NAS, patient and graft survival, comprehensive complication index, early allograft dysfunction, or acute kidney injury. Study protocol magnetic resonance cholangiopancreatography in cDCD patients showed no signs of subclinical biliary strictures. Evaluation of the Swedish national pilot of cDCD LTX with mandatory NRP shows comparable outcomes to a matched DBD cohort with 94.4% 1-year patient and graft survival and no incidence of NAS within the first year.

Hypothermic oxygenated perfusion in liver transplantation: a meta-analysis of randomized controlled trials and matched studies.

Hypothermic oxygenated machine perfusion (HOPE) is a novel organ-preservation technology designed to optimize organ quality. However, the effects of HOPE on morbidity and mortality after liver transplantation remain unclear. This meta-analysis evaluated the potential benefits of HOPE in liver transplantation. The Embase, Web of Science, PubMed, Cochrane Library, and Scopus databases were searched for articles published up to 15 June 2023 (updated on 12 August 2023). Mean differences (MDs), risk ratios (RRs), and 95% confidence intervals were calculated. Eleven studies encompassing five randomized controlled trials and six matched studies were included, with a total of 1000 patients. HOPE did not reduce the incidence of major postoperative complications (RR 0.80), primary non-function (PNF) (RR 0.54), reperfusion syndrome (RR 0.92), hepatic artery thrombosis (RR 0.92), renal replacement therapy (RR 0.98), length of hospital stay (MD, -1.38 days), 1-year recipient death (RR 0.67), or intensive care unit stay (MD, 0.19 days) after liver transplantation. HOPE reduced the incidence of biliary complications (RR 0.74), non-anastomotic biliary strictures (NAS) (RR 0.34), early allograft dysfunction (EAD) (RR 0.54), and acute rejection (RR 0.54). In addition, HOPE improved the retransplantation (RR 0.42) and 1-year graft loss rates (RR 0.38). Compared with static cold storage (SCS), HOPE can reduce the incidence of biliary complications, NAS, EAD, and acute rejection and retransplantation rate after liver transplantation and improve the 1-year graft loss rate. These findings suggest that HOPE, when compared to SCS, can contribute to minimizing complications and enhancing graft survival in liver transplantation. Further research is needed to investigate long-term outcomes and confirm the promising advantages of HOPE in liver transplantation settings.

Prognostic Factors for Non-anastomotic Biliary Strictures Following Adult Liver Transplantation: A Systematic Review and Meta-Analysis.

The development of non-anastomotic biliary strictures (NAS) following orthotopic adult liver transplantation (OLT) is associated with significant morbidity. We performed a systematic review and meta-analysis to identify all prognostic factors for the development of NAS. A systematic review was conducted following preferred reporting items for systematic reviews and meta-analyses (PRISMA) and the meta-analysis of observational studies in epidemiology (MOOSE) guidelines. We used the Newcastle-Ottawa scale to assess the quality of the included studies. Using the random-effects model, we calculated the weighted pooled odds ratios (OR), mean differences (MD), hazard ratios (HR), and 95% confidence intervals (CI) of the risk factors. Based on 19 international studies that included a total of 8269 adult LT patients, we calculated an 8% overall incidence of NAS. In this study, 7 potential prognostic factors were associated with a statistically significant hazard ratio for NAS in pooled analyses including (1) DCD donors compared to DBD donors (2) PSC as an indication for a liver transplant (3) Roux-en-Y bile duct reconstruction compared to duct-to-duct reconstruction (4) hepatic artery thrombosis (5) longer cold ischemia time (6) longer warm ischemia time (7) and total operative times. In this systematic review and meta-analysis, we identified 7 prognostic factors for the development of NAS following OLT. These findings might lay the groundwork for development of diagnostic algorithms to better risk stratify patients at risk for development of NAS.

Reducing cold ischemia time by donor liver "back-table" preparation under continuous oxygenated machine perfusion of the portal vein.

IntroductionCold ischemia time is a well‐known risk factor for the development of non‐anastomotic biliary strictures (NAS) after liver transplantation. End‐ischemic hypothermic oxygenated machine perfusion (HOPE) of DCD liver grafts reduces the incidence of NAS, and has the potential to reduce cold ischemia times. We hypothesized that if a part of the back‐table procedure could be performed under continuous HOPE, cold ischemia times would be reduced.MethodsIn this prospective observational cohort study, all nationwide declined livers that underwent DHOPE‐NMP between July 1st 2021 and January 1st 2022 were included. The back‐table of ten consecutive high‐risk donor livers was performed with ongoing HOPE. Sixty DHOPE‐NMP procedures (August 1st 2017–July 1st 2021) with a conventional back‐table procedure functioned as a control group.ResultsCompared to the control group, this technique led to a decrease in non‐oxygenated back‐table time from median 74 min (IQR 58–92 min) to median 25 min (IQR 21–31 min), p < .01. Median total cold preservation times were reduced from 279 min (IQR 254–297) to 214 min (IQR 132–254), p < .01.ConclusionCold ischemia time of liver grafts can be successfully reduced by over one hour by using portal vein only HOPE during back‐table preparation.

In situ normothermic regional perfusion versus ex situ normothermic machine perfusion in liver transplantation from donation after circulatory death.

In situ normothermic regional perfusion (NRP) and ex situ normothermic machine perfusion (NMP) aim to improve the outcomes of liver transplantation (LT) using controlled donation after circulatory death (cDCD). NRP and NMP have not yet been compared directly. In this international observational study, outcomes of LT performed between 2015 and 2019 for organs procured from cDCD donors subjected to NRP or NMP commenced at the donor center were compared using propensity score matching (PSM). Of the 224 cDCD donations in the NRP cohort that proceeded to asystole, 193 livers were procured, resulting in 157 transplants. In the NMP cohort, perfusion was commenced in all 40 cases and resulted in 34 transplants (use rates: 70% vs. 85% [p=0.052], respectively). After PSM, 34 NMP liver recipients were matched with 68 NRP liver recipients. The two cohorts were similar for donor functional warm ischemia time (21 min after NRP vs. 20 min after NMP; p=0.17), UK-Donation After Circulatory Death risk score (5 vs. 5 points; p=0.38), and laboratory Model for End-Stage Liver Disease scores (12 vs. 12 points; p=0.83). The incidence of nonanastomotic biliary strictures (1.5% vs. 2.9%; p > 0.99), early allograft dysfunction (20.6% vs. 8.8%; p=0.13), and 30-day graft loss (4.4% vs. 8.8%; p=0.40) were similar, although peak posttransplant aspartate aminotransferase levels were higher in the NRP cohort (872 vs. 344 IU/L; p < 0.001). NRP livers were more frequently allocated to recipients suffering from hepatocellular carcinoma (HCC; 60.3% vs. 20.6%; p < 0.001). HCC-censored 2-year graft and patient survival rates were 91.5% versus 88.2% (p=0.52) and 97.9% versus 94.1% (p=0.25) after NRP and NMP, respectively. Both perfusion techniques achieved similar outcomes and appeared to match benchmarks expected for donation after brain death livers. This study may inform the design of a definitive trial.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

Hypothermic Machine Perfusion in Liver Transplantation — A Randomized Trial

BackgroundTransplantation of livers obtained from donors after circulatory death is associated with an increased risk of nonanastomotic biliary strictures. Hypothermic oxygenated machine perfusion of livers may reduce the incidence of biliary complications, but data from prospective, controlled studies are limited.MethodsIn this multicenter, controlled trial, we randomly assigned patients who were undergoing transplantation of a liver obtained from a donor after circulatory death to receive that liver either after hypothermic oxygenated machine perfusion (machine-perfusion group) or after conventional static cold storage alone (control group). The primary end point was the incidence of nonanastomotic biliary strictures within 6 months after transplantation. Secondary end points included other graft-related and general complications.ResultsA total of 160 patients were enrolled, of whom 78 received a machine-perfused liver and 78 received a liver after static cold storage only (4 patients did not receive a liver in this trial). Nonanastomotic biliary strictures occurred in 6% of the patients in the machine-perfusion group and in 18% of those in the control group (risk ratio, 0.36; 95% confidence interval [CI], 0.14 to 0.94; P=0.03). Postreperfusion syndrome occurred in 12% of the recipients of a machine-perfused liver and in 27% of those in the control group (risk ratio, 0.43; 95% CI, 0.20 to 0.91). Early allograft dysfunction occurred in 26% of the machine-perfused livers, as compared with 40% of control livers (risk ratio, 0.61; 95% CI, 0.39 to 0.96). The cumulative number of treatments for nonanastomotic biliary strictures was lower by a factor of almost 4 after machine perfusion, as compared with control. The incidence of adverse events was similar in the two groups.ConclusionsHypothermic oxygenated machine perfusion led to a lower risk of nonanastomotic biliary strictures following the transplantation of livers obtained from donors after circulatory death than conventional static cold storage. (Funded by Fonds NutsOhra; DHOPE-DCD ClinicalTrials.gov number, NCT02584283.)

Normothermic Regional Perfusion or Normothermic Machine Perfusion in Liver Transplantation from Donation after Circulatory Death: A First Comparative Study

Purpose: In-situ normothermic regional perfusion (NRP) and ex-situ normothermic machine perfusion (NMP) aim to improve outcomes of liver transplantation (LT) using donors after circulatory death (DCD). However, these two dynamic preservation strategies have not been compared yet. The aim of this study was to compare outcomes of DCD grafts exposed to NRP with subsequent static cold storage (SCS) versus continuous NMP commenced at the donor centre after a short period of SCS. Method: This international multicentre retrospective study included DCD donor livers that had been subjected to either NRP or NMP. The NRP cohort was transplanted in six French centres participating in the national NRP organ retrieval programme. The NMP cohort was enrolled by four UK and one Belgian centres as part of a multinational randomised controlled trial (COPE). Study endpoints were liver utilisation rate, 2-year patient and graft survival, 30-day graft loss, incidence of clinically manifest biliary strictures, early allograft dysfunction and peak aspartate aminotransferase (AST) levels. Results: Overall, 157 NRP and 34 NMP livers were transplanted, resulting in organ utilisation rates of 70% vs 85% (p = 0.056). The donor and recipient characteristics were similar, including the donor functional warm ischemic time (22 vs 20 min; p = 0.170), UK-DCD risk score (6 vs 5 points; p = 0.15) and lab-MELD scores (12 vs 12 points; p=0.99). NRP livers were more frequently allocated to recipients suffering from hepatocellular carcinoma (62 vs 21%; p < 0.001). HCC-censored 2-year graft and patient survival were 89% vs 88% (p = 0.78) and 93% vs 94% (p = 0.865) after NRP and NMP, respectively, with similar 30-day graft loss (5% vs 9%; p=0.416). The incidence of non-anastomotic biliary strictures (1% vs 3%; p = 0.357) and early allograft dysfunction (20% vs 9%; p = 0.139) were also similar, although peak post-transplant AST levels were lower in the NMP cohort (865 vs 344 IU/l; p < 0.001). Conclusion: Outcomes for both in-situ NRP and continuous ex-situ NMP of DCD grafts appear to match benchmarks expected for DBD livers. This study may inform the appropriate design of a prospective randomised trial comparing the efficacy of both preservation strategies in DCD liver transplantation.PRIZE.01_TablePostoperative outcomesNMP (n=34)NRP (n=157)P30-day graft loss3 (8.8)8 (5.1)0.41630-day patient death2 (5.9)4 (2.5)0.290Early allograft dysfunction3 (8.8)32 (20.4)0.114AST peak 7 days (IU/L)344 (216-701)847 (532-1422)<0.001INR level day 71.1 (1.0-1.2)1.1 (1.0-1.2)0.779Total bilirubin day 7 (mmol/l)29 (16-57)21 (12-40)0.122Non-anastomotic biliary strictures1 (2.9)2 (1.3)0.447Anastomotic stricture6 (17.6)14 (8.9)0.134Hepatic artery thrombosis1 (2.9)4 (2.6)1.000Values are expressed in numbers (percentages) or median (interquartile range) Open table in a new tab Values are expressed in numbers (percentages) or median (interquartile range)

Nonanastomotic Biliary Strictures After Liver Transplantation.

Biliary strictures constitute a major source of morbidity and mortality following liver transplantation (LT). However, studies on the impact of nonanastomotic biliary strictures (NABS) on grafts after LT are limited. 649 patients who underwent LT between January 2013 and June 2017 at our center were retrospectively analyzed and 2.6% (n = 17) of the recipients developed NABS following LT. There were no differences between recipients with and without NABS in indication of LT, graft ischemia time, and type of biliary anastomosis. The incidence of post-LT hepatic artery thrombosis (HAT) (odds ratio [OR]: 15.75, P < .001) and the use of livers from donation after cardiac death (DCD) donors (OR: 8.292, P = .004) were identified as independent significant predictors of NABS by multivariate analysis. Graft survival in those with NABS was significantly worse than in patients without NABS (1-, 3-, and 5-years survival: 64.7%, 57.5%, 0%, vs. 89.8%, 84.0%, 76.4%, P < .001). In conclusion, while the incidence of NABS in our study was relatively low compared to previous reports, NABS was still found to be associated with poor graft survival. Special attention should be paid to NABS occurrence in grafts that develop HAT as well as those from DCD donors.

Study protocol for a multicenter randomized controlled trial to compare the efficacy of end-ischemic dual hypothermic oxygenated machine perfusion with static cold storage in preventing non-anastomotic biliary strictures after transplantation of liver grafts donated after circulatory death: DHOPE-DCD trial

BackgroundThe major concern in liver transplantation of grafts from donation after circulatory death (DCD) donors remains the high incidence of non-anastomotic biliary strictures (NAS). Machine perfusion has been proposed as an alternative strategy for organ preservation which reduces ischemia-reperfusion injury (IRI). Experimental studies have shown that dual hypothermic oxygenated machine perfusion (DHOPE) is associated with less IRI, improved hepatocellular function, and better preserved mitochondrial and endothelial function compared to conventional static cold storage (SCS). Moreover, DHOPE was safely applied with promising results in a recently performed phase-1 study. The aim of the current study is to determine the efficacy of DHOPE in reducing the incidence of NAS after DCD liver transplantation.MethodsThis is an international multicenter randomized controlled trial. Adult patients (≥18 yrs. old) undergoing transplantation of a DCD donor liver (Maastricht category III) will be randomized between the intervention and control group. In the intervention group, livers will be subjected to two hours of end-ischemic DHOPE after SCS and before implantation. In the control group, livers will be subjected to care as usual with conventional SCS only. Primary outcome is the incidence of symptomatic NAS diagnosed by a blinded adjudication committee. In all patients, magnetic resonance cholangiography will be obtained at six months after transplantation.DiscussionDHOPE is associated with reduced IRI of the bile ducts. Whether reduced IRI of the bile ducts leads to lower incidence of NAS after DCD liver transplantation can only be examined in a randomized controlled trial.Trial registrationThe trial was registered in Clinicaltrials.gov in September 2015 with the identifier NCT02584283.

The role of graft reperfusion sequence in the development of non-anastomotic biliary strictures following orthotopic liver transplantation: A meta-analysis

BackgroundLiver transplant is a potential cure for liver failure and hepatic malignancy but there are many techniques which have been described for vascular reconstruction. This study was to compare the prevalence of non-anastomotic biliary stricture and other surgical complications based on Clavien-Dindo scoring system, in initial portal reperfusion (sequential) versus simultaneous or initial artery reperfusion. Data sourcesMeta-analysis of published studies comparing the outcomes of both techniques was carried out. Data search was conducted across the major databases and studies were selected under the guidance of the Cochrane guidelines for systematic reviews and meta-analysis. ResultsSeven studies were included to address the primary and the secondary outcomes. No statistical difference was found in the incidence of non-anastomotic biliary strictures (OR = 0.40; P = 0.14), regardless of reperfusion technique. The pooled estimate of the Clavien-Dindo grading of complications was not significantly different between the techniques, though Clavien-Dindo II complications were higher in the simultaneous or initial artery reperfusion group than the initial portal reperfusion group (OR = 2.73; P = 0.01). Similarly, there was no difference in the operative time, hospital stay and other outcomes addressed in this report. ConclusionsThe available evidence suggests that there is no significant difference demonstrated in the rate of non-anastomotic biliary strictures or other complications, between the two techniques, except for Clavien-Dindo II complications.

Long-term results after transplantation of pediatric liver grafts from donation after circulatory death donors.

BackgroundLiver grafts from donation after circulatory death (DCD) donors are increasingly accepted as an extension of the organ pool for transplantation. There is little data on the outcome of liver transplantation with DCD grafts from a pediatric donor. The objective of this study was to assess the outcome of liver transplantation with pediatric DCD grafts and to compare this with the outcome after transplantation of livers from pediatric donation after brain death (DBD) donors.MethodAll transplantations performed with a liver from a pediatric donor (≤16 years) in the Netherlands between 2002 and 2015 were included. Patient survival, graft survival, and complication rates were compared between DCD and DBD liver transplantation.ResultsIn total, 74 liver transplantations with pediatric grafts were performed; twenty (27%) DCD and 54 (73%) DBD. The median donor warm ischemia time (DWIT) was 24 min (range 15–43 min). Patient survival rate at 10 years was 78% for recipients of DCD grafts and 89% for DBD grafts (p = 0.32). Graft survival rate at 10 years was 65% in recipients of DCD versus 76% in DBD grafts (p = 0.20). If donor livers in this study would have been rejected for transplantation when the DWIT ≥30 min (n = 4), the 10-year graft survival rate would have been 81% after DCD transplantation. The rate of non-anastomotic biliary strictures was 5% in DCD and 4% in DBD grafts (p = 1.00). Other complication rates were also similar between both groups.ConclusionsTransplantation of livers from pediatric DCD donors results in good long-term outcome especially when the DWIT is kept ≤30 min. Patient and graft survival rates are not significantly different between recipients of a pediatric DCD or DBD liver. Moreover, the incidence of non-anastomotic biliary strictures after transplantation of pediatric DCD livers is remarkably low.

Flushing the liver with urokinase before transplantation does not prevent nonanastomotic biliary strictures.

The aim of the present study was to assess whether flushing the donor liver with urokinase immediately before implantation reduces the incidence of nonanastomotic biliary strictures (NASs) after liver transplantation, without causing increased blood loss, analyzed as a historical cohort study. Between January 2005 and October 2012, all liver (re-)transplantations were included. Of the 185 liver transplant recipients included, 63 donor livers between January 2010 and October 2012 received urokinase (study group), whereas the donor liver of 122 consecutive recipients, who served as a historical control group, between January 2005 and January 2010 did not receive urokinase. Basic donor (Eurotransplant donor risk index) and recipient (age, body mass index, laboratory Model for End-Stage Liver Disease score) characteristics did not significantly differ in both groups. Thirty-three recipients developed NASs: 22 in the control group (18%) and 11 (17.5%) in the study group (P = 0.68). Analyzed separately for donation after circulatory death (P = 0.42) or donation after brain death (P = 0.89), there was no difference between the groups in incidence of NAS. Of all the recipients developing NAS, 7 (21%) needed retransplantation and all others were treated conservatively. Autologous blood transfusion requirements did not differ significantly between both groups (P = 0.91), whereas interestingly, more heterologous blood transfusions were needed in the control group (P < 0.001). This study has its limitations by its retrospective character. A multi-institutional prospective study could clarify this issue. In conclusion, arterial flushing of the liver with urokinase immediately before implantation did not lead to a lower incidence of NAS in this study, nor did it lead to increased blood loss.

The Long-Term Prognosis and Treatments of Biliary Complications After Living Donor Liver Transplantation.

Purpose: Biliary complications after living donor liver transplantation (LDLT) are classified as hepaticojejunostomy anastomotic strictures (HJS) and non-anastomotic biliary strictures (NAS). We present a retrospective analysis of the long-term prognosis and treatsments of biliary complications in hepaticojejunostomy. Methods: Between May 2001 and May 2011, 199 LDLTs were performed using S2 monosegment, lateral segment or left lobe grafts. The median age and body weight at LDLT were 1.6 years (0.1-19.5 years) and 9.8 kg (2.6-65.0 kg), respectively. The median observation period was 6.8 years (2.7-12.7 years) after LDLT. Results: The overall incidence of HJS was 18.1% (36/199). Multivariate analysis revealed that left lobe grafts were an independent risk factor for HJS (p=0.034). There were 2 surgical reconstructions, 18 percutaneous biliary drainages (PTBD), 14 double balloon enteroscopies (DBE) and 2 rendezvous penetration procedures were performed for recipients with HJS. The incidence of recurrent HJS was 36.1% (13/36). The graft survival of recipients with and without HJS was 97.2% and 91.4% (p=0.532), respectively, and the graft failures were not due to complications associated with HJS. The overall incidence of NAS was 2.5% (5/199). The causes of NAS were hepatic arterial thrombosis in 1 recipient, intrahepatic bile duct injury associated with ABO-incompatible LDLT in 1 recipient, intrahepatic bile duct injury associated with acute cellular rejection in 2 recipients and unknown etiology in 1 recipient. PTBD were performed for all recipients with NAS, but 1 recipient underwent re-transplantation eight months after the first LDLT due to graft failure secondary to refractory cholangitis. Four recipients were able to undergo PTBD tube removal, but 2 recipients suffered from liver dysfunction. Conclusions: Although HJS occurs even in a late period after LDLT, the long-term prognosis is good because graft failure can be avoided by early diagnosis and treatment. However, NAS can develop into graft failure and suffers from a poor long-term prognosis.

Matrix metalloproteinase 2 genotype is associated with nonanastomotic biliary strictures after orthotopic liver transplantation

Nonanastomotic biliary strictures (NAS) are a serious complication after orthotopic liver transplantation (OLT). Matrix metalloproteinases (MMPs) are involved in connective tissue remodelling in chronic liver disease and complications after OLT. To evaluate the relationship between MMP-2 and MMP-9 gene polymorphisms and NAS. MMP-2 (-1306 C/T) and MMP-9 (-1562 C/T) gene promoter polymorphisms were analysed in 314 recipient-donor combinations. Serum levels of these MMPs were determined in subgroups of patients as well. NAS were identified with various radiological imaging studies performed within 4 years after OLT and defined as any stricture, dilation or irregularity of the intra- or extrahepatic bile ducts of the liver graft followed by an intervention, after exclusion of hepatic artery thrombosis and anastomotic strictures. The average incidence of NAS was 15%. The major clinical risk factor for the development of NAS was PSC in the recipient. The presence of the MMP-2 CT genotype in donor and/or recipient was associated with a significantly higher incidence of NAS, up to 29% when both donor and recipient had the MMP-2 CT genotype (P=0.003). In the multivariate analyses, pre-OLT PSC (hazard ratio 2.1, P=0.02) and MMP-2 CT genotype (hazard ratio 3.5, P=0.003) were found to be independent risk factors for the development of NAS after OLT. No obvious association was found between NAS and the MMP-9 genotype and serum levels of the MMPs. MMP-2 CT genotype of donor and recipient is an independent risk factor, in addition to PSC, for the development of NAS after OLT.

The combination of primary sclerosing cholangitis and CCR5‐Δ32 in recipients is strongly associated with the development of nonanastomotic biliary strictures after liver transplantation

The role of the immune system in the pathogenesis of nonanastomotic biliary strictures (NAS) after orthotopic liver transplantation (OLT) is unclear. A loss-of-function mutation in the CC chemokine receptor 5 (CCR5-Δ32) leads to changes in the immune system, including impaired chemotaxis of regulatory T cells. To investigate the impact of the CCR5-Δ32 mutation on the development of NAS. In 384 OLTs, we assessed the CCR5 genotype in donors and recipients and correlated this with the occurrence of NAS. The CCR5-Δ32 allele was found in 65 (16.9%) recipients. The cumulative incidence of NAS at 5 years was 6.5% in wild-type (Wt) recipients vs 17.2% for carriers of the CCR5-Δ32 allele (P<0.01). In recipients with CCR5-Δ32, 50% of all NAS occurred >2 years after OLT, compared with 10% in the Wt group. In multivariate regression analysis, the adjusted risk of developing NAS was four-fold higher in recipients with CCR5-Δ32 (P<0.01). The highest risk of NAS was seen in patients transplanted for primary sclerosing cholangitis (PSC), who also carried CCR5-Δ32 (relative risk 5.4, 95% confidence interval 2.2-12.9; P<0.01). Donor CCR5 genotype had no impact on the occurrence of NAS. Patients with the CCR5-Δ32 mutation have a four-fold higher risk of developing NAS, compared with Wt recipients. This risk is even higher in patients with CCR5-Δ32 transplanted for PSC. Late development of NAS is significantly more present in patients with CCR5-Δ32. These data suggest that the immune system plays a critical role in the development of NAS after OLT.

Liver transplantation following donation after cardiac death: An analysis using matched pairs

Grafts from donation after cardiac death (DCD) donors are used to increase the number of organs available for liver transplantation. There is concern that warm ischemia may impair graft function. We compared our DCD recipients with a case-matched group of donation after brain death (DBD) recipients. Between January 2002 and April 2008, 39 DCD grafts were transplanted. These were matched with 39 DBD recipients on the basis of identified variables that had a significant impact on mortality. These were used to individually match DCD and DBD patients with similar predictive mortality. We compared patient/graft survival, primary non-function (PNF), and rates of complications. Of all liver transplants, 6.1% were DCD grafts. PNF occurred twice in the DCD group. The incidence of nonanastomotic biliary strictures (NABS; 20.5% versus 0%, P = 0.005) and hepatic artery stenosis (HAS; 12.8% versus 0%, P = 0.027) in the DCD group was higher. One-year (79.5% versus 97.4%, P = 0.029) and 3-year (63.6% versus 97.4%, P = 0.001) graft survival was lower in the DCD group. Three-year patient survival was also lower (68.2% versus 100%, P < 0.0001). Our study is the first to use case-matched patients and compare groups with similar predictive mortality. There was a higher incidence of NABS and HAS in the DCD group. NABS were likely a result of warm ischemia. HAS may have been due to ischemia or arterial injury during retrieval. The DCD group had significantly poorer outcomes, but DCD grafts remain a valuable resource. With careful donor/recipient selection, minimization of ischemia, and good postoperative care, acceptable results can be achieved.

Is Roux-en-Y choledochojejunostomy an independent risk factor for nonanastomotic biliary strictures after liver transplantation?

Biliary reconstruction using Roux-en-Y choledochojejunostomy has been suggested as a risk factor for the development of nonanastomotic biliary strictures (NAS) after liver transplantation. Roux-en-Y reconstruction, however, is preferentially used in patients transplanted for primary sclerosing cholangitis (PSC), and the disease itself is also associated with a higher incidence of NAS. The aim of this study was to determine whether Roux-en-Y reconstruction is really an independent risk factor for NAS. A series of 486 consecutive adult liver transplants were studied. Biliary reconstruction in patients transplanted for PSC was either by Roux-en-Y choledochojejunostomy or by duct-to-duct anastomosis, depending on the quality of the recipient's extrahepatic bile duct. Univariate and multivariate statistical analyses were used to identify risk factors for the development of NAS. The overall incidence of NAS was 16.5% (80/486). In univariate analyses, the following variables were significantly associated with NAS: PSC as the indication for transplantation, type of biliary reconstruction (Roux-en-Y versus duct-to-duct), and postoperative cytomegalovirus infection. After multivariate logistic regression analysis, PSC as the indication for transplantation (odds ratio, 2.813; 95% confidence interval, 1.624-4.875; P < 0.001) and postoperative cytomegalovirus infection (odds ratio, 2.098; 95% confidence interval, 1.266-3.477; P = 0.004) remained as independent risk factors for NAS. Biliary reconstruction using Roux-en-Y choledochojejunostomy was not identified as an independent risk factor for NAS. In conclusion, the association between Roux-en-Y choledochojejunostomy and NAS observed in previous studies can be explained by the more frequent use of Roux-en-Y reconstruction in patients with PSC. Roux-en-Y reconstruction itself is not an independent risk factor for NAS. Liver Transpl 15:924-930, 2009. (c) 2009 AASLD.

Biliary Complications After Liver Transplantation From Maastricht Category-2 Non-Heart-Beating Donors

There are unresolved issues regarding the security of liver transplantation with non-heart-beating donors (NHBDs). Recently, an increased incidence of biliary complications, mainly intrahepatic ischemic-type biliary strictures, has been described after controlled NHBDs. We studied the incidence and risk factors for biliary complications among uncontrolled NHBDs recipients compared with a large population of HBD recipients. Overall, 16.8% of patients in the HBD group and 41.7% of patients in the NHBD group suffered any type of biliary complication (P=0.66). However, the incidence of nonanastomotic biliary strictures was significantly greater in the NHBD group (P<0.001). Multivariate analysis showed that independent risk factors for nonanastomotic strictures were hepatic artery thrombosis (relative risk; 98.7) and receiving a liver from a NHBD (relative risk; 47.1). If this type of donors is accepted as a source of liver organs, the high incidence of biliary complications should be considered and efforts should be made to decrease ischemic injury.

THE POTENTIAL ROLE OF CLASS II ANTIGENS IN RECURRENCE OF PSC FOLLOWING LIVER TRANSPLANTATION.

143 Background: The etiology of PSC remains unknown; however, the association of PSC with the autoimmune HLA haplotype DR3 has given support to the hypothesis that related gene products may act directly in the pathogenesis of the disease. Reviewing 169 consecutive liver transplant recipients with PSC since March 1985, we found a significantly increased frequency of HLA DR3 and DR6 (48.5% and 42%) compared to a contemporary group of 827 organ donors (23.3% and 29%). In addition, we found a high incidence of non-anastomotic biliary strictures (NAS) in PSC patients, which has led us to the conclusion that PSC recurs frequently following liver transplantation (OLT). Aim: To determine whether Class II antigens are associated with NAS following OLT in PSC patients. Methods: In order to determine the role of HLA DR3 and DR6 in the development of NAS post OLT in the UW era, 77 PSC patients with HLA DR3 and/or DR6 were compared with a control group of 289 non-PSC patients. Results: The incidence of NAS in all 77 PSC patients was 17% compared to 6.2% in the Non-PSC control group (p<0.003). However, in 16 PSC patients without DR3 and DR6 antigens, the incidence of NAS was only 6.3%, which is not different from the control group. In contrast in 61 PSC patients with DR3 and/or DR6, the incidence of NAS was 19.7%. (Table)Table: NAS and HLA DR3, DR6: Conclusions: We found that PSC patients who expressed the DR3 and/or DR6 antigens have an increased incidence of non-anastomotic biliary strictures compared to PSC patients who lack these antigens. These findings suggest that HLA DR3 and DR6 are either markers for recurrence of PSC, or their gene products may act directly in the development of this disease process.