M. Thamara P. R. Perera

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.

Liver transplantation: Issues for the next 20 years

The growing numbers of potential transplant recipients on waiting lists is increasingly disproportionate to the supply of cadaveric donor organs. The hope for the next 20 years is that supply will satisfy demand. This requires both a reduction in indications for the procedure and an increase in the transplants performed. A multi‐pronged approach is needed to increase cadaveric organ donation, generating enthusiasm for donation among both the general public and hospital staff. Accurate assessment of marginal grafts with stringent criteria known to predict graft function will diminish wastage of organs. Methods of rehabilitating marginal grafts during extracorporeal perfusion will increase organ availability. Supply of non‐heart beating donors can be greatly expanded and protocols developed with ethical consent to optimize their initial function despite warm ischemia. Splitting livers that fulfill selection criteria, thus providing for two recipients, should be universally applied with acceptable incentives to those units who do not directly benefit. A proportion of recipients, though not those transplanted for autoimmune disease, will be spared the side‐effects of immunosuppression thanks to immune tolerance. Protocols for close monitoring of those patients for rejection during treatment withdrawal must be carefully observed. In addition to gene therapy, it is highly likely that hepatocyte transplantation will replace orthotopic grafting in patients without cirrhosis, especially for inherited metabolic diseases. It is much more difficult to envisage that heterologous stem cell transplantation or xenotransplantation will have clinical impact in the next 20 years, although research in those areas has obvious long‐term potential.

Specialist Early and Immediate Repair of Post-laparoscopic Cholecystectomy Bile Duct Injuries Is Associated With an Improved Long-term Outcome

Introduction:A majority of bile duct injuries (BDI) sustained during laparoscopic cholecystectomy require formal surgical reconstruction, and traditionally this repair is performed late. We aimed to assess long-term outcomes after repair, focusing on our preferred early approach. Methods:A total of 200 BDI patients [age 54(20–83); 64 male], followed up for median 60 (5–212) months were assessed for morbidity. Factors contributing to this were analyzed with a univariate and multivariate analysis. Results:A total of 112 (56%) patients were repaired by specialist hepatobiliary surgeons [timing of repair: immediate, n = 28; early (<21 days), n = 43; and late (>21 days) n = 41], whereas 45 (22%) underwent repair by nonspecialist surgeons before specialist referral [immediate, n = 16; early, n = 26 and late, n = 03]. Outcomes after immediate and early repairs were comparable to late repairs when performed by specialists [recurrent cholangitis:11%, 12%, and 10%; P = 0.96, NS; re-stricture:18%,5%, and 29%; P = 0.01; nonsurgical intervention: 14%, 5%, and 24%; P<0.03; redo surgery: 4%, 2%, and 5%; P = 0.81, NS; overall morbidity: 21%, 14%, and 39%; P<0.02]. On multivariate analysis, immediate and early repairs done by nonspecialist surgeons were independent risk factors (P < 0.05) for recurrent cholangitis [50% and 27%], re-stricturing (75% and 61%), redo reconstructions (31% and 61%), and overall morbidity (75% and 84%). Conclusion:Immediate and early repair after BDI results in comparable, if not better long-term outcomes compared to late repair when performed by specialists.

A randomized trial of normothermic preservation in liver transplantation

Liver transplantation is a highly successful treatment, but is severely limited by the shortage in donor organs. However, many potential donor organs cannot be used; this is because sub-optimal livers do not tolerate conventional cold storage and there is no reliable way to assess organ viability preoperatively. Normothermic machine perfusion maintains the liver in a physiological state, avoids cooling and allows recovery and functional testing. Here we show that, in a randomized trial with 220 liver transplantations, compared to conventional static cold storage, normothermic preservation is associated with a 50% lower level of graft injury, measured by hepatocellular enzyme release, despite a 50% lower rate of organ discard and a 54% longer mean preservation time. There was no significant difference in bile duct complications, graft survival or survival of the patient. If translated to clinical practice, these results would have a major impact on liver transplant outcomes and waiting list mortality.Normothermic machine perfusion of the liver improved early graft function, demonstrated by reduced peak serum aspartate transaminase levels and early allograft dysfunction rates, and improved organ utilization and preservation times, although no differences were seen in graft or patient survival.

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.

Clinical practice: management of biliary atresia.

Biliary atresia is a rare, serious and challenging disease in newborn children. Its aetiology remains unknown. Optimal management at specialist centres with resultant better overall outcomes is achieved through a multidisciplinary team approach. The Kasai portoenterostomy performed early in life remains the only surgical repair procedure. Two thirds of patients will clear their jaundice after a Kasai procedure, but only about one third will retain their livers after the first decade of life. Failure of this procedure leaves liver transplantation as the only chance for survival, and this disease is the commonest indication for liver transplantation in children. With modern medical care and refinements in surgical techniques, survival after either or both of these procedures is about 90%. Early referral to specialist centres and long-term specialist care remains the key to successful treatment of this condition.

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.

Pre-emptive liver transplantation for primary hyperoxaluria (PH-I) arrests long-term renal function deterioration

BACKGROUND Primary hyperoxaluria-I (PH-I) is a serious metabolic disease resulting in end-stage renal disease. Pre-emptive liver transplantation (PLT) for PH-I is an option for children with early diagnosis. There is still little information on its effect on long-term renal function in this situation. METHODS Long-term assessment of renal function was conducted using Schwartzs formula (estimated glomerular filtration rate-eGFR) in four children (Group A) undergoing PLT between 2002 and 2008, and a comparison was done with eight gender- and sex-matched controls (Group B) having liver transplantation for other indications. RESULTS All patients received a liver graft from a deceased donor. Median follow-up for the two groups was 64 and 94 months, respectively. One child in Group A underwent re-transplantation due to hepatic artery thrombosis, while acute rejection was seen in one. A significant difference was seen in eGFR at transplant (81 vs 148 mL/min/1.73 m(2)) with greater functional impairment seen in the study population. In Group A, renal function reduced by 21 and 11% compared with 37 and 35% in Group B at 12 and 24 months, respectively. At 2 years post-transplantation, there was no significant difference in eGFR between the two groups (72 vs 100 mL/min/1.73 m(2), respectively; P = 0.06). CONCLUSIONS Renal function remains relatively stable following pre-emptive LTx for PH-I. With early diagnosis of PH-I, isolated liver transplantation may prevent progression to end-stage renal disease and the need for renal 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.

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.