John Isaac

Donation After Cardiac Death Liver Transplant Recipients Have an Increased Frequency of Acute Kidney Injury

Donation after cardiac death (DCD) liver transplantation is associated with an increased frequency of hepato‐biliary complications. The implications for renal function have not been explored previously. The aims of this single‐center study of 88 consecutive DCD liver transplant recipients were (1) to compare renal outcomes with propensity‐risk‐matched donation after brain death (DBD) patients and (2) in the DCD patients specifically to examine the risk factors for acute kidney injury (AKI; peak creatinine ≥2 times baseline) and chronic kidney disease (CKD; eGFR <60 mL/min/1.73 m2). During the immediate postoperative period DCD liver transplantation was associated with an increased incidence of AKI (DCD, 53.4%; DBD 31.8%, p = 0.004). In DCD patients AKI was a risk factor for CKD (p = 0.035) and mortality (p = 0.017). The cumulative incidence of CKD by 3 years post‐transplant was 53.7% and 42.1% for DCD and DBD patients, respectively (p = 0.774). Importantly, increasing peak perioperative aspartate aminotransferase, a surrogate marker of hepatic ischemia reperfusion injury, was the only consistent predictor of renal dysfunction after DCD transplantation (AKI, p < 0.001; CKD, p = 0.032). In conclusion, DCD liver transplantation is associated with an increased frequency of AKI. The findings suggest that hepatic ischemia reperfusion injury may play a critical role in the pathogenesis of post‐transplant renal dysfunction.

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. Liver Transpl 20:713‐723, 2014.

A preoperative predictive score of pancreatic fistula following pancreatoduodenectomy

BACKGROUND Various factors are related to the occurrence of postoperative pancreatic fistula (POPF) following pancreatoduodenectomy (PD). Some of the strongest are identified intra- or postoperatively, which limits their utility in predicting this complication. The preoperative prediction of POPF permits an individualized approach to patient consent and selection, and may influence postoperative management. This study sought to develop and test a score to predict POPF. METHODS A post hoc analysis of a prospectively maintained database was conducted. Consecutive patients were randomly selected to modelling and validation sets at a ratio of 2 :1, respectively. Patient data, preoperative blood tests and physical characteristics of the gland (assessed from preoperative computed tomography images) were subjected to univariate and multivariate analysis in the modelling set of patients. A score predictive of POPF was designed and tested in the validation set. RESULTS Postoperative pancreatic fistula occurred in 77 of 325 (23.7%) patients. The occurrence of POPF was associated with 12 factors. On multivariate analysis, body mass index and pancreatic duct width were independently associated with POPF. A risk score to predict POPF was designed (area under the receiver operating characteristic curve: 0.832, 95% confidence interval 0.768-0.897; P < 0.001) and successfully tested upon the validation set. CONCLUSIONS Preoperative assessment of a patients risk for POPF is possible using simple measurements. The present risk score is a valid tool with which to predict POPF in patients undergoing PD.

Scoring System to Predict Pancreatic Fistula After Pancreaticoduodenectomy: A UK Multicenter Study

OBJECTIVE To validate a preoperative predictive score of postoperative pancreatic fistula (POPF). Other risk factors for POPF were sought in an attempt to improve the score. BACKGROUND POPF is the major contributor to morbidity after pancreaticoduodenectomy (PD). A preoperative score [using body mass index (BMI) and pancreatic duct width] to predict POPF was tested upon a multicenter patient cohort to assess its performance. METHODS Patients undergoing PD at 8 UK centers were identified. The association between the score and other pre-, intra-, and postoperative variables with POPF was assessed. RESULTS A total of 630 patients underwent PD with 141 occurrences of POPF (22.4%). BMI, perirenal fat thickness, pancreatic duct width on computed tomography and at operation, bilirubin, pancreatojejunostomy technique, underlying pathology, T stage, N stage, R status, and gland firmness were all significantly associated with POPF. The score predicted POPF (P < 0.001) with a higher predictive score associated with increasing severity of POPF (P < 0.001). Stepwise multivariate analysis of pre-, intra-, and postoperative variables demonstrated that only the score was consistently associated with POPF. A table correlating the risk score to actual risk of POPF was created. CONCLUSIONS The predictive score performed well and could not be improved. This provides opportunities for individualizing patient consent and selection, and treatment and research applications.

First human liver transplantation using a marginal allograft resuscitated by normothermic machine perfusion

Liver transplantation (LT) is plagued by lack of suitable donor organs, and the current waiting list mortality in the United Kingdom approaches 20%. This situation remains unchanged despite progressive expansion of the use of donors previously considered to be too high risk for transplant. Primary nonfunction (PNF) in LT recipients remains the main obstacle to further increasing the use of marginal grafts. The increasing reliance on marginal extended criteria donor livers from older donors, with higher body mass indices or ischemia times is not without consequence. The potential benefit of using these grafts is often offset by post-transplant complications including PNF, delayed graft function, and ischemia-type biliary strictures that are especially seen in recipients of donation after cardiac death (DCD) livers. Therefore, organ discard rates have been increasing, most commonly for degree of graft steatosis, inadequate perfusion, or prolonged warm and/or cold ischemia time. Ischaemia/reperfusion injury is the fundamental cause of graft damage following static cold storage. The detrimental effect of cold storage is greatest in marginal organs, with PNF representing the worst end of the spectrum of graft dysfunction. The actual risk for a particular graft is difficult to predict though the reported incidence for grafts from extended criteria donors, including those from DCD with cold ischemia time exceeding 8 hours, could be as high as 30%. Recipients of DCD grafts are more likely to experience PNF and delayed graft function, and incidence of ischemia-type biliary strictures remains a problem. Over the last decade, machine perfusion technology has been investigated to improve the quality of marginal liver grafts based on the encouraging experimental data and results from the clinical experiences. The most profound impact of normothermic machine liver perfusion (NMLP) is derived from this technology’s unique ability to assess viability during storage. On the basis of our preclinical perfusion experiments on discarded livers, we developed a viability testing protocol for livers deemed not transplantable then subjected to NMLP. Here, we present the first report of transplantation of a graft salvaged by postischemia NMLP with a follow-up period of 15 months.

Is It Time to Extend Liver Acceptance Criteria for Controlled Donors After Cardiac Death

Background. Donation after cardiac death (DCD) has reemerged as potential way to increase donor liver availability. Earlier, programs with DCD liver transplantation used conservative donor criteria to allow safe results. Successful initial outcomes allowed extended DCD criteria to address transplant demand. Methods. A total of 63 DCD liver grafts were used during the study period in carefully selected recipients. These were divided into two groups: “Standard” DCD within conservative criteria (n=33; age ≤60 years, body mass index <30 kg/m2, donor warm ischemia time ≤30 min, and cold ischemia time ≤8 hr) and “Extended” DCD beyond these criteria (n=30). We compared donor and recipient characteristics and postoperative outcomes, including patient and graft survival. Results. Both groups had satisfactory initial function; liver graft function at 1, 7, and 30 days after liver transplantation were similar. Median follow-up period was 25 and 18.5 months for Standard and Extended criteria DCD grafts, respectively, with 1-year patient and graft survival of 88% and 82% for the Standard group vs. 90% and 90% for the Extended. Overall, 8 of 63 (13%) patients developed biliary complications; however, the incidence was not different between the Standard and Extended groups. Seven early deaths occurred, four and three in the Standard and Extended groups, respectively. Conclusions. Recipients of DCDs beyond conventional acceptance criteria have equivalent early outcomes to standard DCD grafts. With careful selection of donors and recipients, these grafts can be safely used to expand the donor pool.

Normothermic Machine Perfusion of Deceased Donor Liver Grafts Is Associated With Improved Postreperfusion Hemodynamics.

Background Graft reperfusion poses a critical challenge during liver transplantation and can be associated with hemodynamic instability/postreperfusion syndrome. This is sequel to ischemia-reperfusion injury and normothermic machine preservation (NMP) may affect hemodynamic changes. Herein, we characterize postreperfusion hemodynamics in liver grafts after NMP and traditional cold preservation. Materials and methods Intraoperative records of patients receiving grafts after NMP (n = 6; NMP group) and cold storage (CS) (n = 12; CS group) were compared. The mean arterial pressure (MAP) was defined as the average pressure in the radial artery during 1 cardiac cycle by invasive monitoring. Postreperfusion syndrome was defined as MAP drop greater than 30% of baseline, lasting for 1 minute or longer within the first 5 minutes from graft reperfusion. Results Donor, recipient, demographics, and surgical parameters were evenly matched. Normothermic machine preservation grafts were perfused for 525 minutes (395-605 minutes) after initial cold ischemic time of 91 minutes (73-117 minutes), whereas in CS group cold ischemic time was 456 minutes (347-685 minutes) (P = 0.001). None developed postreperfusion syndrome in the NMP group against n = 2 (16.7%) in CS group (P = 0.529). Normothermic machine preservation group had better intraoperative MAP at 90 minutes postreperfusion (P = 0.029), achieved with a significantly less vasopressor requirement (P = <0.05) and less transfusion of blood products (P = 0.030) compared with CS group. Conclusions Normothermic machine perfusion is associated with a stable intraoperative hemodynamic profile postreperfusion, requiring significantly less vasopressor infusions and blood product transfusion after graft reperfusion and may have benefit to alleviate ischemia-reperfusion injury in liver transplantation.

Preoperative Thromboelastography as a Sensitive Tool Predicting Those at Risk of Developing Early Hepatic Artery Thrombosis after Adult Liver Transplantation

Background Whilst causes of hepatic artery thrombosis (HAT) after liver transplantation (LT) are multifactorial, early HAT (E-HAT) remains pertinent complication impacting on graft and patient survival. Currently there is no screening tool that would identify patients with increased risk of developing E-HAT. Methods We analyzed the native procoagulant state of LT recipients, identified through pretransplant thromboelastographic (TEG) data among other known risk factors, to identify risk factors for E-HAT. Results The outcomes of 828 adult patients undergoing LT between 2008 and 2013 were analyzed. Overall, 79 (9.5%) patients experienced HAT, E-HAT was diagnosed in 23, and in the remainder this was “late” HAT. The maximum amplitude (MA) on preoperative TEG was significantly higher in patients diagnosed with E-HAT compared with those who did not (71.2 mm vs 57.9 mm; P < 0.0001). Receiver operating characteristic analysis with the cutoff value for MA of 65 mm or greater returned area under the curve of 0.750 (P < 0.001) predicting E-HAT with a sensitivity of 70%. A total of 7% of patients with an MA of 65 mm or greater went on to develop E-HAT (hazard ratio, 5.28; 95% confidence interval, 2.10-12.29; P < 0.001), whereas only 1.2% patients with an MA less than 65 mm experienced E-HAT. Conclusions Preoperative TEG may reliably identify group of recipients at greater risk of developing E-HAT, and intense surveillance and anticoagulation prophylaxis may avoid this serious complication after LT.

Aetio-pathogenesis and the management of spontaneous liver bleeding in the West: a 16-year single-centre experience

BACKGROUND Spontaneous liver bleeding (SLB) is a rare but potentially fatal complication. In contrast to the East, various benign pathologies are the source of SLB in the West. An accurate diagnosis and a timely implementation of appropriate treatment are crucial in the management of these patients. The present study presents a large Western experience of SLB from a specialist liver centre. METHODS A retrospective analysis of patients presented with SLB between January 1995 and January 2011. RESULTS Sixty-seven patients had SLB, 44 (66%) were female and the median age at presentation was 47 years. Abrupt onset upper abdominal pain was the presenting symptom in 65 (97%) patients. The aetiology for SLB was hepatic adenoma in 27 (40%), hepatocellular carcinoma (HCC) in 17 (25%) and various other liver pathologies in the rest. Emergency treatment included a conservative approach in 42 (64%), DSA and embolization in 6 (9%), a laparotomy and packing in 6 (9%) and a liver resection in 11 (16%) patients. Eleven (16%) patients had further planned treatments. Seven (10%) died during the same admission but the mortality was highest in patients with HELLP syndrome. At a median follow-up of 54 months all patients with benign disease are alive. The 1-, 3- and 5-year survival of patients with HCC was 59%, 35% and 17%, respectively. CONCLUSION SLB is a life-threatening complication of various underlying conditions and may represent their first manifestation. The management should include initial haemostasis followed by appropriate staging investigations to provide a definitive treatment for each individual patient.

Vasculobiliary complications following adult right lobe split liver transplantation from the perspective of reconstruction techniques

Split liver transplantation (SLT) compensates for the organ shortage and provides an alternative solution for recipients disadvantaged by a smaller body size. Variations in the hepatic arterial anatomy and reconstructive techniques may lead to more technical complications, and we sought to analyze the incidence and risk factors of vasculobiliary complications with respect to reconstructive techniques. We identified 171 adult right lobe SLT procedures and 1412 whole liver transplantation (WLT) procedures between January 2000 and June 2012 and compared the results of these 2 groups. In the SLT group, arterial reconstruction techniques were classified into 4 subgroups (I‐IV), and biliary reconstruction was classified into 2 groups [duct‐to‐duct (DD) anastomosis and Roux‐en‐Y hepaticojejunostomy (RH)]. Specific surgical complications were analyzed against reconstruction techniques. The overall incidence of vascular and biliary complications in the SLT group was greater than that in the WLT group (P = 0.009 and P = 0.001, respectively). There was no difference in hepatic artery thrombosis (HAT), but we saw a tendency toward early HAT in the presence of multiple hepatic arteries supplying the right lobe graft (group IV; 20%) in comparison with the other arterial reconstruction groups (P = 0.052). No difference was noticed in the overall incidence of biliary complications in either DD or RH recipients across 4 arterial reconstruction groups. When the arterial reconstruction involved a right hepatic artery (groups II and III) combined with a DD biliary anastomosis, there was a significant preponderance of biliary complications (P = 0.04 and P = 0.01, respectively). There was no survival difference between SLT and WLT grafts. In conclusion, the complications of SLT are directly related to arterial and biliary reconstruction techniques, and this classification helps to identify high‐risk reconstructive techniques. Liver Transpl 21:63‐71, 2015.