Nonanastomotic Biliary Strictures Research Articles

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.

Simultaneous Lung-abdominal Organ Procurement From Donation After Circulatory Death Donors Reduces Donor Hepatectomy Time.

Prolonged organ procurement time impairs the outcome of donation after circulatory death (DCD) and liver transplantation (LiT). Our transplant team developed a simultaneous, rather than sequential, lung-abdominal organ explantation strategy for DCD donation to prioritize liver procurement. We evaluated whether this change in strategy effectively reduced donor hepatectomy time (dHT), without affecting donor pneumonectomy time (dPT), and influenced LiT and lung transplantation outcome. All lung-abdominal and abdominal-only transplant procedures between 2010 and 2020 were analyzed in this retrospective cohort study. Relationships were assessed between the year of transplant and dHT and dPT (univariate linear regression), 1-y patient and graft survival, primary graft dysfunction, and nonanastomotic biliary strictures (univariate logistic regression). Fifty-two lung-abdominal and 110 abdominal-only DCD procedures were analyzed. A significant decrease in dHT was noted in lung-abdominal (slope -1.14 [-2.14; -0.15], P = 0.026) but not in abdominal-only procedures; dPT did not increase. There were no significant associations between the year of transplant and nonanastomotic biliary strictures frequency, primary graft dysfunction incidence, 1-y patient, and graft survival. Simultaneous organ procurement in multiorgan lung-abdominal DCD procedures is feasible, and effectively shortened dHT without affecting lung transplantation outcome. No impact on LiT outcome was observed; however, larger multicenter studies are needed.

Late occurrence of nonanastomotic biliary stricture after liver transplantation

Late occurrence of nonanastomotic biliary stricture after liver transplantation

Effects of machine perfusion strategies on different donor types in liver transplantation: a systematic review and meta-analysis.

The increasing use of extended criteria donors (ECD) sets higher requirements for graft preservation. Machine perfusion (MP) improves orthotopic liver transplantation (OLT) outcomes, but its effects on different donor types remains unclear. The authors' aim was to assess the effects of hypothermic machine perfusion (HMP), normothermic machine perfusion (NMP), or normothermic regional perfusion (NRP) versus static cold storage (SCS) on different donor types. A literature search comparing the efficacy of MP versus SCS in PubMed, Cochrane, and EMBASE database was conducted. A meta-analysis was performed to obtain pooled effects of MP on ECD, donation after circulatory death (DCD), and donor after brainstem death. Thirty nine studies were included (nine randomized controlled trials and 30 cohort studies). Compared with SCS, HMP significantly reduced the risk of non-anastomotic biliary stricture (NAS) [odds ratio (OR) 0.43, 95% confidence interval (CI) 0.26-0.72], major complications (OR 0.55, 95% CI 0.39-0.78), and early allograft dysfunction (EAD) (OR 0.46, 95% CI 0.32-0.65) and improved 1-year graft survival (OR 2.36, 95% CI 1.55-3.62) in ECD-OLT. HMP also reduced primary non-function (PNF) (OR 0.40, 95% CI 0.18-0.92) and acute rejection (OR 0.62, 95% CI 0.40-0.97). NMP only reduced major complications in ECD-OLT (OR 0.56, 95% CI 0.34-0.94), without favorable effects on other complications and survival. NRP lowered the overall risk of NAS (OR 0.27, 95% CI 0.11-0.68), PNF (OR 0.43, 95% CI 0.22-0.85), and EAD (OR 0.58, 95% CI 0.42-0.80) and meanwhile improved 1-year graft survival (OR 2.40, 95% CI 1.65-3.49) in control DCD-OLT. HMP might currently be considered for marginal livers as it comprehensively improves ECD-OLT outcomes. NMP assists some outcomes in ECD-OLT, but more evidence regarding NMP-ECD is warranted. NRP significantly improves DCD-OLT outcomes and is recommended where longer non-touch periods exist.

Post-transplant biliary complications using liver grafts from deceased donors older than 70 years: Retrospective case-control study.

The shortage of liver grafts and subsequent waitlist mortality led us to expand the donor pool using liver grafts from older donors. To determine the incidence, outcomes, and risk factors for biliary complications (BC) in liver transplantation (LT) using liver grafts from donors aged > 70 years. Between January 1994 and December 31, 2019, 297 LTs were performed using donors older than 70 years. After excluding 47 LT for several reasons, we divided 250 LTs into two groups, namely post-LT BC (n = 21) and without BC (n = 229). This retrospective case-control study compared both groups. Choledocho-choledochostomy without T-tube was the most frequent technique (76.2% in the BC group vs 92.6% in the non-BC group). Twenty-one patients (8.4%) developed BC (13 anastomotic strictures, 7 biliary leakages, and 1 non-anastomotic biliary stricture). Nine patients underwent percutaneous balloon dilation and nine required a Roux-en-Y hepaticojejunostomy because of dilation failure. The incidence of post-LT complications (graft dysfunction, rejection, renal failure, and non-BC reoperations) was similar in both groups. There were no significant differences in the patient and graft survival between the groups. Moreover, only three deaths were attributed to BC. While female donors were protective factors for BC, donor cardiac arrest was a risk factor. The incidence of BC was relatively low on using liver grafts > 70 years. It could be managed in most cases by percutaneous dilation or Roux-en-Y hepaticojejunostomy, without significant differences in the patient or graft survival between the groups.

Machine perfusion techniques for liver transplantation - A meta-analysis of the first seven randomized-controlled trials

Machine perfusion is increasingly being tested in clinical transplantation. Despite this, the number of large prospective clinical trials remains limited. The aim of this study was to compare the impact of machine perfusion vs. static cold storage (SCS) on outcomes after liver transplantation. A systematic search of MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials (CENTRAL) was conducted to identify randomized-controlled trials (RCTs) comparing "post-transplant" outcomes following machine perfusion vs. SCS. Data were pooled using random effect models. Risk ratios (RRs) were calculated for relevant outcomes. The quality of evidence was rated using the GRADE-framework. Seven RCTs were identified (four on hypothermic oxygenated [HOPE] and three on normothermic machine perfusion [NMP]), including a total number of 1,017 patients. Both techniques were associated with significantly lower rates of early allograft dysfunction (NMP: n= 41/282, SCS: n= 74/253, RR 0.50, 95% CI 0.30-0.86, p=0.01, I2= 39%; HOPE: n= 45/241, SCS: n= 97/241, RR 0.48, 95% CI 0.35-0.65, p<0.00001, I2= 5%). The HOPE approach led to a significant reduction in major complications (Clavien Grade ≥IIIb; HOPE: n= 90/241; SCS: n= 117/241, RR 0.76, 95% CI 0.63-0.93, p=0.006, I2= 0%), "re-transplantation" (HOPE: n= 1/163; SCS: n= 11/163; RR 0.21, 95% CI 0.04-0.96, p=0.04; I2= 0%) and graft loss (HOPE: n= 7/163; SCS: n= 19/163; RR 0.40, 95% CI 0.17-0.95, p=0.04; I2= 0%). Both perfusion techniques were found to 'likely' reduce overall biliary complications and non-anastomotic strictures. Although this study provides the highest current evidence on the role of machine perfusion, outcomes remain limited to a 1-year follow-up after liver transplantation. Comparative RCTs and large real-world cohort studies with longer follow-up are required to enhance the robustness of the data further, thereby supporting the introduction of perfusion technologies into routine clinical practice. CRD42022355252. For a decade, two dynamic perfusion concepts have increasingly been tested in several transplant centres worldwide. We undertook the first systematic review and meta-analysis and identified seven published RCTs, including 1,017 patients, evaluating the effect of machine perfusion (hypothermic and normothermic perfusion techniques) compared to static cold storage in liver transplantation. Both perfusion techniques were associated with lower rates of early allograft dysfunction in the first week after liver transplantation. Hypothermic oxygenated perfusion led to a reduction in major complications, lower "re-transplantation" rates and better graft survival. Both perfusion strategies were found to 'likely' reduce overall biliary complications and non-anastomotic biliary strictures. This study provides the highest current evidence on the role of machine perfusion. Outcomes remain limited to a 1-year post-transplant follow-up. Larger cohort studies with longer follow-up and clinical trials comparing the perfusion techniques are required. This is especially relevant to provide clarity and optimise implementation processes further to support the commissioning of this technology worldwide.

Treatment of Non-Anastomotic Biliary Strictures after Liver Transplantation: How Effective Is Our Current Treatment Strategy?

Non-anastomotic biliary strictures (NAS) are a common cause of morbidity and mortality after liver transplantation. All patients with NAS from 2008 to 2016 were retrospectively analyzed. The success rate and overall mortality of an ERCP-based stent program (EBSP) were the primary outcomes. A total of 40 (13.9%) patients with NAS were identified, of which 35 patients were further treated in an EBSP. Furthermore, 16 (46%) patients terminated EBSP successfully, and nine (26%) patients died during the program. All deaths were caused by cholangitis. Of those, one (11%) patient had an extrahepatic stricture, while the other eight patients had either intrahepatic (3, 33%) or combined extra- and intrahepatic strictures (5, 56%). Risk factors of overall mortality were age (p = 0.03), bilirubin (p < 0.0001), alanine transaminase (p = 0.006), and aspartate transaminase (p = 0.0003). The median duration of the stent program was 34 months (ITBL: 36 months; IBL: 10 months), and procedural complications were rare. EBSP is safe, but lengthy and successful in only about half the patients. Intrahepatic strictures were associated with an increased risk of cholangitis.

A randomized-controlled trial of ischemia-free liver transplantation for end-stage liver disease

Ischemia-reperfusion injury (IRI) has thus far been considered as an inevitable component of organ transplantation, compromising outcomes, and limiting organ availability. Ischemia-free organ transplantation is a novel approach designed to avoid IRI, with the potential to improve outcomes. In this randomized, controlled clinical trial, recipients of livers from donors after brain death were randomly assigned to receive either an ischemia-free or a 'conventional' transplant. Primary end point was the incidence of early allograft dysfunction. Secondary end points included complications related to graft IRI. 65 out of 68 randomized patients underwent transplants and were included in the analysis. 32 patients received ischemia-free liver transplantation (IFLT), and 33 received conventional liver transplantation (CLT). Early allograft dysfunction occurred in 2 (6%) randomized to IFLT and in 8 (24%) randomized to CLT (difference, -18%; 95% CI, -35% to -1%; P=.044). Post-reperfusion syndrome occurred in 3 (9%) randomized to IFLT and in 21 (64%) randomized to CLT (difference, -54%; 95% CI, -74% to -35%; P < .001). Non-anastomotic biliary strictures diagnosed with protocol magnetic resonance cholangiopancreatography at 12 months were observed in 2 recipients (8%) randomized to IFLT and in 9 recipients (36%) randomized to CLT (difference, -28%; 95% CI, -50% to -7%; P = .014). The comprehensive complication index at one year after transplantation was 30.48 (95% CI, 23.25-37.71) in the IFLT group vs 42.14 (95% CI, 35.01-49.26) in the CLT group (difference, -11.66; 95% CI, -21.81 to -1.51; P = .025). Among patients with end-stage liver disease, IFLT, compared with conventional approach, significantly reduced complications related to ischemia reperfusion injury. Chictr.org. ChiCTR1900021158 IMPACT AND IMPLICATIONS: Ischemia reperfusion injury has thus far been considered as an inevitable event in organ transplantation, compromising outcomes and limiting organ availability. Ischemia-free liver transplantation is a novel approach of transplanting donor livers without interruption of blood supply. We showed that in patients with end-stage liver disease, ischemia-free liver transplantation, compared with conventional approach led to reduced complications related to ischemia reperfusion injury in this randomized trial. This new approach is expected to change the current practice in organ transplantation improving transplant outcomes, increasing organ utilization, while providing a clinical model to delineate the impact of organ injury on alloimmunity.

Individualized Biliary Reconstruction Techniques in Liver Transplantation: Five Years’ Experience of a Single Institution

BackgroundTo summarize the experience of individualized biliary reconstruction techniques in deceased donor liver transplantation and explore potential risk factors for biliary stricture. MethodsWe retrospectively collected medical records of 489 patients undergoing deceased donor liver transplantation at our center between January 2016 and August 2020. According to anatomical and pathological conditions of donor and recipient biliary ducts, patients’ biliary reconstruction methods were divided into six types. We summarized the experience of six different reconstruction methods and analyzed the biliary complications’ rate and risk factors after liver transplantation. ResultsAmong 489 cases of biliary reconstruction methods during liver transplantation, there were 206 cases of type I, 98 cases of type II, 96 cases of type III, 39 cases of type IV, 34 cases of type V, and 16 cases of type VI. Biliary tract anastomotic complications occurred in 41 cases (8.4%), including 35 cases with biliary stricture (7.2%), 9 cases with biliary leakage (1.8%), 19 cases with biliary stones (3.9%), 1 case with biliary bleeding (0.2%), and 2 cases with biliary infection (0.4%). One of 41 patients died of biliary tract bleeding and one died of biliary infection. Thirty-six patients significantly improved after treatment, and 3 patients received secondary transplantation. Compared with patients without biliary stricture, a higher warm ischemic time was observed in patients with non-anastomotic stricture and more leakage of bile in patients with an anastomotic stricture. ConclusionThe individualized biliary reconstruction methods are safe and feasible to decrease perioperative anastomotic biliary complications. Biliary leakage may contribute to anastomotic biliary stricture and cold ischemia time to non-anastomotic biliary stricture.

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.

Normothermic Machine Perfusion for Declined Livers: A Strategy to Rescue Marginal Livers for Transplantation.

Organ waste is a major cause of the donor liver shortage. Roughly 67% of recovered organ donors have liver utilization annually. A new technology called normothermic machine perfusion (NMP) offers a way to recover marginal and declined livers for transplant. We report interim results of the RESTORE trial (FDA investigational drug exemption trial NCT04483102) that aims to transplant NMP-treated livers that would otherwise be discarded. Declined livers were screened for NMP eligibility (eg donation after circulatory death [DCD] grafts with warm ischemic time <40 minutes, donation after brain death [DBD] grafts with cold ischemic time <8 hours). Livers meeting pre-NMP eligibility criteria received NMP using the OrganOx metra device for a minimum of 4 hours. All NMP-treated livers meeting the viability criteria were transplanted to consented recipients. Over 22 months, 60 declined livers from three organ procurement organizations (OPOs; 40 DCD and 20 DBD donor livers) were offered, and 22 livers (10 DCD and 12 DBD livers) met the pre-NMP eligibility. After NMP, 16 of 22 livers passed viability testing and were transplanted into needy recipients (median Model for End-Stage Liver Disease [MELD] score of 8, range 6 to 24), resulting in a 72.7% rescue rate (50% DCD, 91.7% DBD). The rate of early allograft dysfunction was 31.3%, but there were no graft-related deaths, primary nonfunction, or instances of nonanastomotic biliary strictures. Interim results of the RESTORE trial suggest that a sizable number of declined livers can be reclaimed. They are safe for transplantation and can enable lower MELD patients at high risk of morbidity and mortality to receive lifesaving grafts while offering OPOs a way to allocate more livers and reduce organ waste.

Cholangioscopy in Recurrent Cholangitis after Liver Transplantation: Selective Guidewire Cannulation of Non-anastomotic Biliary Stricture

Cholangioscopy in Recurrent Cholangitis after Liver Transplantation: Selective Guidewire Cannulation of Non-anastomotic Biliary Stricture

PERFUSION PROGRAMMES START-UP AND VIABILITY ASSESSMENT: A PRACTICAL GUIDE TO EX-SITU NORMOTHERMIC MACHINE PERFUSION IN LIVER TRANSPLANTATION

Machine perfusion of the liver has been an increasingly adopted approach to overcome the shortcomings of static cold storage, that are most prominent in extended criteria donors. Normothermic machine perfusion (NMP) safety and efficacy were demonstrated in several prospective trials and multiple cohort series. The real-world benefits of this approach are liver functional assessment and extended preservation times. In this review, we aim to provide information regarding the practical aspects of starting an NMP programme and pragmatic guidance towards assessing liver viability for teams new to this field. There are two key areas of focus in assessing liver viability, examining both the hepatocyte and cholangiocyte compartments. Analysis of these areas can predict risk of primary non-function and non-anastomotic biliary strictures, respectively. There is a learning curve in adopting and gaining confidence with the NMP technology. Viability assessment allows transplantation of more marginal livers, but a cautious approach is advised for new centres entering the field.

HYPOTHERMIC MACHINE PERFUSION OF THE LIVER. THE REASONS FOR SUCCESS

Machine perfusion is an attractive preservation technique to improve outcomes after transplantation. Based on underlying protective mechanisms two main concepts are described today, both with the same goal to provide oxygen to ischemic tissue. While normothermic machine perfusion (NMP) is rather labor intense and conveys its highest effect when performed instead of cold storage, the concept of hypothermic machine perfusion (HMP) is simpler and used after cold storage in the recipient centre. During re-oxygenation mitochondria immediately initiate the inflammatory cascade of ischemia-reperfusion-injury (IRI), although those features appear significantly less pronounced under cold conditions. In contrast to a normothermic perfusion, hypothermic techniques lead to a functional recovery of the respiratory chain and the Krebs cycle, thereby reloading cellular energy and metabolizing toxic metabolites, including Succinate. Although the preconditioning of mitochondria with cold oxygenation prior to transplantation is repeatedly described since the early days of organ transplantation, an increasing body of supportive literature is seen only recently. Newly published randomized controlled trials confirm this protection and demonstrate less organ injury, less complications including non-anastomotic biliary strictures, lower acute rejection rates and better graft survivals with the use of hypothermic oxygenated perfusion (HOPE). Of great interest is also the simplicity of HOPE, particularly when applied through the portal vein only, enabling the performance of a liver split during perfusion without the risk of arterial injury. In addition, there is increasing evidence how to assess liver viability during HMP through real-time spectroscopy of mitochondrial metabolism. Perfusate levels of Flavin mononucleotide (FMN), released from complex-I during reperfusion correlate with posttransplant complications and graft survival. This review article describes all features of HMP and addresses remaining challenges of this beneficial preservation technique.

Endoscopic therapy using a self-expandable metallic stent with an anti-migration system for postorthotopic liver transplantation anastomotic biliary stricture.

BACKGROUNDEndoscopic therapy using multiple plastic stents (MPSs) is the standard therapy for postorthotopic liver transplantation (p-OLT) anastomotic biliary stricture (ABS). However, this approach demands repeated procedures. Recent studies using fully covered self-expandable metallic stents (FCSEMS) have shown encouraging results, but migration occurs in 10% to 40% of cases. The objective of this retrospective study was to evaluate the efficacy of endoscopic treatment using FCSEMS with an anti-migration system (Am-FCSEMS) in patients with p-OLT ABS.AIMTo evaluate the efficacy of endoscopic treatment using an Am-FCSEMS in patients with p-OLT ABS.METHODSThis study was conducted in a private tertiary care centre in São Paulo, Brazil and was approved by our institution's Human Research Committee. From April 2018 to October 2020, regardless of previous endoscopic treatment (MPS or FCSEMS), 17 patients with p-OLT ABS and indications for endoscopic therapy were included in this study. The exclusion criteria were pregnancy, nonanastomotic biliary or hilar stricture, hepatic artery stenosis/thrombosis, isolated biliary fistulae, a distance shorter than 2 cm from the stricture to the hepatic hilum, and patient refusal. The primary endpoint was the efficacy of p-OLT ABS endoscopic treatment using an Am-FCSEMS that remained in place for a 12-mo period. Biliary sphincterotomy was performed in patients with native papilla, and an Am-FCSEMS (10 mm in final diameter and 60 or 80 mm in length) was placed (HanarostentTM MI Tech, Co). Balloon stricture dilation was performed only if necessary to introduce the stent.RESULTSThree patients were excluded due to loss to follow-up before stent removal. Among the 14 patients included and followed, 7 were women, and the average age was 56 years (range: 28-76). The average period of Am-FCSEMS placement was 362 ± 109 d. Technical success occurred in all 14 patients (100%). There were no cases of distal stent migration. Complete resolution of the stricture occurred in 13/14 patients (92.85%). Adverse events occurred in 3/14 patients (21.42%): 2 patients with mild acute pancreatitis (14.28%) and 1 patient (7.14%) with stent dysfunction (occlusion by biliary sludge and stones, which was treated endoscopically without the need for stent removal). No deaths occurred related to therapy. All stents were removed using foreign body forceps or snares without difficulty. After Am-FCSEMS removal, all 13 patients who had ABS resolution were followed-up for an average of 411 ± 172 d, and there was no stricture recurrence or need for further endoscopic therapy.CONCLUSIONIn this retrospective study, endoscopy therapy using an Am-FCSEMS for p-OLT ABS was safe and effective, with a high stricture resolution rate that was probably due to the absence of stent migration.

Machine Perfusion as "Comfort Zone": What Are Key Challenges of Liver Viability Assessment Today?

Machine Perfusion as "Comfort Zone": What Are Key Challenges of Liver Viability Assessment Today?

Predicting Early Allograft Function After Normothermic Machine Perfusion.

Normothermic ex situ liver perfusion is increasingly used to assess donor livers, but there remains a paucity of evidence regarding criteria upon which to base a viability assessment or criteria predicting early allograft function. Perfusate variables from livers undergoing normothermic ex situ liver perfusion were analyzed to see which best predicted the Model for Early Allograft Function score. One hundred fifty-four of 203 perfused livers were transplanted following our previously defined criteria. These comprised 84/123 donation after circulatory death livers and 70/80 donation after brain death livers. Multivariable analysis suggested that 2-h alanine transaminase, 2-h lactate, 11 to 29 mmol supplementary bicarbonate in the first 4 h, and peak bile pH were associated with early allograft function as defined by the Model for Early Allograft Function score. Nonanastomotic biliary strictures occurred in 11% of transplants, predominantly affected first- and second-order ducts, despite selection based on bile glucose and pH. This work confirms the importance of perfusate alanine transaminase and lactate at 2-h, as well as the amount of supplementary bicarbonate required to keep the perfusate pH > 7.2, in the assessment of livers undergoing perfusion. It cautions against the use of lactate as a sole indicator of viability and also suggests a role for cholangiocyte function markers in predicting early allograft function.

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.

CEUS detection of biliary ischaemia during the first 4 weeks after liver transplantation predicts non-anastomotic biliary stricture

Biliary ischaemia is an important factor in the pathogenesis of non-anastomotic biliary stricture (NAS) after liver transplantation (LT). Contrast-enhanced ultrasound (CEUS) can be used to detect biliary ischaemia, but no study has examined the utility of CEUS in predicting NAS. To evaluate whether repeated CEUS as a non-invasive method of biliary ischaemia can identify NAS. Consecutive LT patients who underwent CEUS examinations at 1-4 weeks after LT from September 2012 to December 2015 at our institution were included. The CEUS images and clinical data were analysed. Among 116 eligible LT patients, 39 (33.6%) were diagnosed with NAS within 1 year after LT. The patients with NAS had a significantly higher CEUS score at weeks 2-4 (all P < 0.05) and a higher slope of CEUS score progression (0.480 vs -0.044, P < 0.001). The accuracy of CEUS in identifying NAS improved over time after LT, reaching its maximum at week 4, with a sensitivity of 66.7%, a specificity of 87.9%, a positive predictive value (PPV) of 75.9%, a negative predictive value (NPV) of 82.3%, and an accuracy of 80.2%in the full cohort when a CEUS score≥3 was used as the cut-off. Multivariate analysis identified gamma-glutamyl transpeptidase (GGT), alanine transaminase (ALT) and the CEUS score at week 4 as independent predictors of NAS. In the task of identifying NAS, an NAS score combining the above 3 variables at week 4 showed areas under the receiver operating characteristic curve of 0.88 (95%CI, 0.78-0.99) in the estimation group (n = 60) and 0.82 (95%CI, 0.69-0.96) in the validation group (n = 56). An NAS score cut-off of 0.396 identified 87.2%of NAS cases in the estimation group, with a PPV of 93.3%; and 75.0%of NAS cases in the validation group, with a PPV of 58.8%. CEUS examination during the first 4 weeks is useful in assessing the risk of NAS within 1 year after LT. In particular, an NAS score combining the CEUS score, GGT level, and ALT level at week 4 can be used to accurately predict the risk of NAS in LT patients.