Objectives: This study investigated a fixed coordinator–directed donor management strategy’s impact on donated liver quality, as determined by definitive biopsy results.
Materials and Methods: We collected donated liver biopsy results from donations both before and after implementing a fixed coordinator-directed donor management strategy. This strategy involved full-time attendance by a donor coordinator and continued resuscitation of brain-dead donors. All donations took place in a single organ procurement unit. We also followed up results of biopsies from the Liver Transplantation Center database of Namazi Hospital in Shiraz, Iran.
Results: We compared biopsy findings of 192 livers donated from 2012 to 2013 (group A) with 276 livers donated from 2015 until August 2016 (group B). Data analysis showed that 67 livers (34.9%) in group A were rejected for transplant owing to severe steatosis in 17 (8.9%), moderate/severe fibrosis in 9 (4.7%), moderate/severe necrosis in 28 (14.6%), and 13 (6.8%) rejected for other pathologies. Among group B livers, 59 (21.4%) were not deemed suitable for transplant owing to severe steatosis in 37 (13.5%), moderate/severe fibrosis in 6 (2.1%), and moderate/severe necrosis in 16 (5.7%). Overall, steatosis was found in 94 livers (49.2%) in group A versus 175 livers (63.3%) in group B (P = .007). Donor age in group A averaged 36.5 years versus 47.9 years in group B (P = .02). Necrosis was found in 33 livers (17.2%) in group A and 22 livers (7.9%) in group B (P = .008). One-month survival rates were 95.3% and 96.3% for groups A and B (P = .08).
Conclusions: Donated liver disqualification before transplant noticeably decreased despite the shift in demographic patterns from 2012 to 2016. In group A, brain-dead liver donors were younger and more often died from trauma, whereas group B donors had more cerebrovascular accident-induced deaths. This achievement took place alongside increased rates of steatosis and decreased rates of necrosis.
Key words : Brain death, Frozen section, Graft dysfunction, Liver necrosis, Liver transplantation
Brain death is a catastrophic molecular and cellular pathophysiologic cascade that can lead to multiple devastating consequences. Hemodynamic instability, the potential for ischemia/reperfusion injury, and concomitant organ failure may result from both the original cause of brain death and the series of events associated with the inflammatory state induced by brain injury.1-3 Donor brain death is a significant risk factor in liver transplant outcomes because marginal liver utilization is associated with higher risk of primary nonfunction of the organ.4,5
In deceased-donor organ transplant, clinicians attempt life-saving procedures by retrieving organs from deceased donors whose activated inflammatory systems can lead to graft dysfunction. However, significant changes in donor demographics and cause of death, in addition to the increasing organ shortage, have exerted tremendous pressure on organ transplant teams. In many transplant centers, the wide availability of organ donations from young deceased donors who died due to trauma has all but ended, and the era of elderly potential donors (above 65 years) whose brain death resulted from cardiovascular or cerebrovascular accidents has begun.6
Although many studies have demonstrated the safety and even advantages of liver transplant from elderly donors when well selected and performed,6,7 we know that the incidence of a variety of liver diseases increases with age, and the ability of the liver to resist external injuries during and after transplant similarly declines. No organ donation and transplant expert has experienced the demographic changes in donors as much as those in Iran. In 2009, the mean age of donors in Iran was 31.7 years, with trauma being the cause of death in the majority (57%) of cases.8 At that time, “advanced age” was used as an excuse by transplant teams to refuse some organ donors—an objection that is now only a historical memory.
In addition to criteria for liver donor selection, many strategies have been proposed and practiced to histologically assess deceased-donor livers both before and after retrieval. Among the well-established protocols is the use of frozen sectioning before organ retrieval, intraoperatively, or before performing transplant surgery. Liver biopsy before organ recovery has been demonstrated to be “logistically feasible” for decreasing futile organ retrieval.9 This method has significantly decreased the proportion of attempted liver recoveries that did not end in transplant (from 31.9% to 8.7%; P = .009).
Because of the special nature of liver donation and transplant in Iran, which involves multiple hospitals that may be located in different cities, histologic examination is performed after organ retrieval and before transplant surgery at the transplant center. Before reaching our organ procurement unit (OPU), potential brain-dead donors are handled medically in nearly 120 covered peripheral hospitals. They get transferred to the intensive care unit of the OPU after clinicians have made a primary determination of neurologic (brain) death, considering primary inclusion and exclusion criteria, and obtaining family consent for organ donation. Until 2014, our practice consisted of primary medical resuscitation of the donor and starting a family interview process that could last from hours to days. The interval between first assessment of the donor and organ retrieval was highly variable using this protocol. During this time, medical management duty would be delegated to intensivists and personnel of those hospitals, which did not have a close connection to the OPU.
Owing to the expansion of human and financial resources in 2014, we executed a new management protocol. Thereafter, the organ donation coordinator was responsible for donor management until either organ retrieval or cardiac arrest, in the case of delay or failure to obtain family consent.
We found no other studies that compared 2 organ donor management strategies based on biopsy findings. For this study, we decided to investigate the impact of the full-time donor management protocol on our donors’ liver biopsy findings as an indicator of the donors’ physiologic condition before brain death and the quality of the medical management.
Materials and Methods
In this retrospective study, we collected donated liver biopsy results from 468 brain-dead donors from January 2012 to December 2013 and from January 2015 to August 2016, after the implementation of a fixed coordinator-directed donor management strategy. All biopsies studies were from frozen sectioning. Fixed coordinator-directed management involves having a full-time, fixed-attendance coordinator and continuing resuscitation of the brain-dead donor by regulating fluids and electrolytes, stabilizing acid-base disturbances, and tapering inotropic agents. All donations took place in the OPU of Masih Daneshvari Hospital in Tehran. We also followed the results of biopsies from the Liver Transplantation Center database of Namazi Hospital in Shiraz. All specimens were interpreted by a single experienced pathologist. The Levine test and t test were performed to assess possible differences in mean values. A Kaplan-Meier study was performed to assess 1-month survival of the organ recipients.
We compared biopsy findings of 192 donated livers sent to Namazi Hospital from 2012 to 2013 (group A) with 276 livers donated from 2015 until August 2016 (group B). Donors’ average age in group A was 36.5 years versus 47.9 in group B (P = .02) (Table 1). Severe steatosis and moderate-to-severe necrosis or fibrosis were reasons for livers being disqualified for transplant. Retrospective data analysis showed that 67 livers (34.8%) in group A were rejected for transplant owing to severe steatosis (17, 8.9%), moderate/severe fibrosis (9, 4.7%), or moderate/severe necrosis (28, 14.6%) and 13 (6.8%) for other pathologies. Among 276 biopsy results of group B livers, 59 (21.3%) were not deemed suitable for transplant owing to severe steatosis in 37 (13.5%), moderate/severe fibrosis in 6 (2.1%), and moderate/severe necrosis in 6 (5.7%). Overall, steatosis was found in 94 livers (49.2%) in group A versus 175 livers (63.3%) in group B (P = .007). Varying degrees of necrosis were found in 3 livers (17.2%) in group A compared with 22 livers (7.9%) in group B (P = .008). Steatosis was the most common finding in both groups, although slightly more prevalent in group B (63.3% vs 49.2%; P = .007).
In comparing the 2 observed study periods, we found that the mean time interval between the first approach for family consent and actual liver donation decreased from 3.4 to 2.2 days (P = .009). The mean duration of intubation of potential donors decreased from 8.6 days in group A to 5.8 days in group B (P = .05). One-month survival rates increased slightly, from 95.3% in group A to 96.3% in group B, based on results from a Kaplan-Meier study (P = .08) (Table 1).
Although the average age of our donors increased significantly from 36.5 years to 47.9 years from 2012 to 2016, surprisingly, the percentage of disqualified livers fell from 34.8% to 21.3%. Because of the growing incidence of potential donor deaths due to cardiovascular or cerebrovascular accident and the decrease in deaths due to trauma, we needed to develop more sophisticated management strategies to meet the increasing demand for organs. Thus, we changed our protocol for the medical management of potential donors to full-time coordinator-directed management until the moment of organ donation.
Serrano and colleagues reported on a fascinating study of the utilization of liver donors aged more than 60 years. They found that the incidence of chronic and acute rejection, vascular complications, and infections did not statistically differ between recipients of livers from elderly or younger donors. The incidence of anastomotic biliary strictures was also similar in the 2 groups, although nonanastomotic biliary strictures were seen more often in the group who received livers from the older donors (17.0% vs 4.9%; OR, 3.9; P = .025).10 Chapman’s group reported similar short- and long-term graft survival data, including from donors older than 70 years.11 More recently, Lué and associates discussed several considerations for older donated livers. They concluded that, although liver function does not seem to decrease with aging alone, the liver’s lack of capacity to resist external injuries makes higher donor age a risk factor for future complications.4 Reese and colleagues described increased donor age as well as cold ischemia times as factors negatively influencing 90-day allograft survival.12 These findings are at variance with our study, in which 30-day survival did not significantly differ between liver transplant recipients of group A and B donors (P = .08). Many studies have shown the inferiority of organs (including liver) obtained from deceased donors to those from living donors.13-15 However, this controversy has only heated up since advanced donor management protocols began to be recommended and applied.16-18
In developing countries, especially in the Middle East, organ transplant is accompanied by casual and difficult-to-manage complications. As a result of weak transplant-amenity structures at many medical centers, donors may be transferred to the OPUs of selected hospitals. Additionally, owing to lack of sufficient knowledge about brain death and organ donation in medical societies, possible donors may be overlooked in many medical centers. To counteract these trends, we took full responsibility for donor resuscitation as well as the persistent care of potential deceased donors. The result was a significant drop in the rate of moderate-to-severe necrosis among donor-liver biopsies: from 14.6% to 5.7% (P < .001).
In our study, 2 livers from pediatric donors were missed as a result of prolonged hospitalization prior to brain death. In these cases, the 13-month-old and 2.5-year-old brain-dead donors had severe acidosis and hemodynamic instability in the course of their hospitalization. Liver biopsy showed severe necrosis, and, consequently, the organs were disqualified for transplant. In contrast, 2 patients with end-stage liver disease received a transplant of a severely steatotic liver (> 60% of macrovesicular change) in an effort to save their lives. Unfortunately, they died shortly after transplant because of primary graft nonfunction.
Although recent studies19,20 have questioned the accuracy of donor liver biopsy results using frozen sectioning before transplant, it appears to be the best tool for conclusively evaluating donated livers. We might have been somewhat negligent about correlating severe necrosis with bad donor management by failing to equalize all possible variables due to limited sample size, but overall improvement of donated livers was a definite observation.
The marked decrease in donated liver disqualification at our center from 2012-2013 to 2015-2016 was a significant achievement. Despite the shift in demographic patterns from young brain-dead donors with trauma to those with cerebrovascular accident-induced death, improved outcomes may be due to the intensive, fixed coordinator-directed medical management of donors until family consent or cardiac arrest and the shorter time between family interview to consent. Despite the increasing age of donors and the accompanying prevalence of steatosis, the prevalence of necrosis has decreased significantly because of intensive management.
Volume : 15
Issue : 1
Pages : 269 - 272
DOI : 10.6002/ect.mesot2016.P135
From the 1Organ Procurement Unit, Lung Transplantation Research Center, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran; and the 2Shiraz Transplant Center, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
Acknowledgements: The authors declare that they have no sources of funding for this study, and they have no conflicts of interest to declare.
Corresponding author: Farahnaz Sadegh Beigee, Organ Procurement Unit, Lung Transplantation Research Center, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Darabad, Niavaran, Tehran, 19569-44413, Iran
Table 1. Liver Donor Demographics and Biopsy Results (N = 468)