In living donor liver transplantation (LDLT), the hepatic lobe donor incurs a measurable risk of death.1 Unfortunately, the actual risk of death after a donor hepatectomy is unknown, because of the absence of a sufficient database to allow an accurate determination of this infrequent but devastating outcome. Current estimates of donor death rates are derived from either survey data or single-center reports. The use of survey data (in which transplant programs are retrospectively queried regarding clinical outcomes) is inexact because of incomplete follow-up of all donor outcomes and bias toward reporting favorable results. Single-center reports are likely to provide more complete follow-up data, but are limited by the relatively small numbers of cases. In the absence of a definitive means to record all donor deaths, the medical literature has become replete with anecdotal reports of deaths that in many cases are based on verbal communications, circular references, or frankly unsubstantiated outcomes.2, 3 As a result, the actual number of donor deaths after LDLT is the subject of considerable speculation. The purpose of this analysis is to provide the most complete, although likely imperfect, estimate and description of the documented deaths of hepatic lobe donors after LDLT.
The actual risk of death in hepatic lobe donors for living donor liver transplantation (LDLT) is unknown because of the lack of a comprehensive database. In the absence of a definitive estimate of the risk of donor death, the medical literature has become replete with anecdotal reports of donor deaths, many of which cannot be substantiated. Because donor death is one of the most important outcomes of LDLT, we performed a comprehensive survey of the medical and lay literature to provide a referenced source of worldwide donor deaths. We reviewed all published articles from the medical literature on LDLT and searched the lay literature for donor deaths from 1989 to February 2006. We classified each death as “definitely,” “possibly,” or “unlikely” related to donor surgery. We identified 19 donor deaths (and one additional donor in a chronic vegetative state). Thirteen deaths and the vegetative donor were “definitely,” 2 were “possibly,” and 4 were “unlikely” related to donor surgery. The estimated rate of donor death “definitely” related to donor surgery is 0.15%. The rate of donor death which is “definitely” or “possibly” related to the donor surgery is 0.20%. This analysis provides a source document of all identifiable living liver donor deaths, provides a better estimate of donor death rate, and may provide an impetus for centers with unreported deaths to submit these outcomes to the liver transplantation community. Liver Transpl 12:1485-1488, 2006. © 2006 AASLD.
MATERIALS AND METHODS
We reviewed all articles from the PubMed electronic biomedical search and retrieval system for all articles regarding donor outcomes for LDLT published from 1989 to February 2006.4 In addition, we used the Internet to search the lay literature through 2 other Web sites to locate donor deaths that may have not been reported in the medical literature.5, 6 We recorded all published donor deaths and classified each as “definitely,” “possibly,” and “unlikely” related to the donor operation. Deaths that were “definitely” linked to the operation resulted from a surgical complication that could be attributed to the hepatectomy, i.e., sepsis or liver failure. Deaths that were “possibly” linked to donor surgery included those where the patient died of suicide, including self-inflicted drug overdose, which could possibly be related to psychological changes induced by the donation process. Deaths that were deemed “unlikely” to be related to the donor operation occurred more than a year after the procedure and were from causes that seemed to be unrelated to any conceivable complication of the surgery. The date of death for each donor was based on the date of the associated publication or, if available, the actual year of death. Additional information for selected cases from Europe was provided by one of the authors (R.A.) through the European Liver Transplantation Registry. Estimates of donor death rate were made from U.S. (United Network for Organ Sharing [UNOS]; http://www.unos.org/data/about/viewDataReports.asp) and European (European Liver Transplantation Registry, provided by one of the authors [R.A.]).
We found 19 deaths of living hepatic lobe donors and one donor in a chronic vegetative state for over 1.5 years after surgery. Thirteen deaths (and one additional donor in a chronic vegetative state) were “definitely” related to the donor surgery, 2 were “possibly” related, and 4 were “unlikely” related. Brief vignettes of each event abstracted from the available literature are provided in Table 1. The total estimated number of LDLTs performed in the United States and Europe is 4598 (Table 2). The estimated rate of donor death “definitely” related to donor surgery is 7 (0.15%) of 4598. The rate of donor death “definitely” (7 patients) or “possibly” (2 patients) related to the donor surgery is 9 (0.20%) of 4598. The median/mean time from transplantation to death was 11/37.9 days in the donors whose deaths were “definitely” related to surgery. The most common cause of deaths “definitely” related to surgery was sepsis (5 patients), followed by liver failure (2 patients), unknown (2 patients), myocardial infarction, cerebral hemorrhage, pulmonary embolus, and peptic ulcer disease (1 patient each).
|Donor deaths “definitely” related to donor hepatectomy|
|11||2003||Japan||A mother in her late 40s donated a right lobe and died 9 months later from complications of hepatic failure.|
|12||2002||USA||A 57-year-old brother donated a right lobe and developed gastric gas gangrene and Clostridium perfringens infection 3 days after surgery and died.|
|13||2005||Brazil||A 31-year-old female right lobe donor of unknown relationship to the recipient died 7 days after surgery from a subarachnoid hemorrhage.|
|14||2003||India||A donor of unknown age and unknown relationship to the recipient donated an unknown lobe and died 10 days after surgery of unknown causes.|
|15||2003||India||A 52-year-old wife donated an unknown lobe and became comatose 48 hours after surgery from unknown causes and remains in chronic vegetative state.|
|16–18||1993||Germany||A 29-year-old mother donated a left lateral lobe and died of a pulmonary embolus 48 hours after surgery.|
|18, 19||2000||Germany||A 38-year-old father donated a right lobe, and 32 days after developing progressive hepatic failure, died during transplantation of acute cardiac failure. The cause of the donor's death was attributed to Berardinelli-Seip syndrome, a lipodystrophy syndrome characterized by loss of body fat, diabetes, hepatomegaly, and acanthosis nigricans.|
|18, 20||2000||France||A 32-year-old brother donated a right lobe and developed sepsis and multiple organ system failure 11 days after surgery and died of septic shock 3 days later.|
|18||2000||Europe||A 57-year-old wife donated a right lobe and died of sepsis and multiple organ system failure 21 days after surgery.|
|21, 22||1999||USA||A 41-year-old half-brother donated a right lobe and died of pancreatitis and sepsis 1 month later.|
|22, 23||1997||USA||A mother of unknown age donated an unknown lobe to a pediatric recipient and died 3 days after surgery of unknown causes.|
|24||2005||Asia||A 50-year-old mother donated a right hepatic lobe. She had no history of peptic ulcer disease and received a 2-week course of H2 antagonist. She died 10 weeks after surgery from an autopsy-proven duodenal ulcer with a duodenocaval fistula causing air embolism.|
|25||2006||Asia||A 39-year-old male “close relative” who donated an unknown lobe died of a myocardial infarction 4 days after donation. The patient reportedly had a preoperative electrocardiogram and treadmill test.|
|26||2005||Egypt||A brother of unknown age who donated a right lobe died of complications of sepsis from a bile leak 1 month after donation.|
|Donor deaths “possibly” related to donor hepatectomy|
|27||2005||USA||A 35-year-old brother donated a right lobe and died of a self-induced drug overdose 23 months later.|
|27||2005||USA||A 50-year-old uncle donated a right lobe and died of a self-inflicted gunshot wound to the head 22 months after donation.|
|Donor deaths “unlikely” to be related to donor hepatectomy|
|28||2003||Asia||A donor of unknown age and relationship to the recipient who donated an unknown lobe died of unknown causes during exercise 3 years after donation.|
|27, 29||2002||USA||A 35-year-old boyfriend donated a right lobe and died in a nonsuicidal occupational pedestrian-train accident 2 years after donation. A lone railroad car rolling at high speed struck and killed the donor while he was on duty at his job for the railroad.|
|16||2003||Germany||A 30-year-old father donated a left lateral segment and died of complications of amyotrophic lateral sclerosis 11 years after successful donation.|
|30||2003||Japan||A male donor in his 40s of unknown relationship to the recipient donated an unknown lobe died 10 years postoperatively after an apparently unrelated surgery.|
|Location||Reference||Estimated number of living donor liver transplantations|
This report describes all of the documented donor deaths that we were able to identify after an extensive search of the medical and lay literature. As such, this report provides the most comprehensive description of all known worldwide donor deaths after LDLT. However, the available documentation surrounding the circumstances of some of these cases is sketchy at best. In addition, we acknowledge that this report does not likely include all living donor deaths after LDLT. There are likely other deaths that we were unable to locate in the literature or deaths that have not been reported, because Asia and the United States have not had ongoing mandatory reporting systems in place to record outcomes for all living donors. However, data from Europe may be more complete because the European Liver Transplantation Registry performs random audits each year at contributing centers.7 Recently, UNOS has mandated that U.S. liver transplant centers must report outcomes of living donors who are taken to the operating room for the purpose of donation. However, this data set has not been in place long enough to record any undiscovered donor deaths. We did not access non-English language search engines. As a result, there may be reports of deaths in non-English sources that we have not discovered.
We found that most of the deaths occurred from apparent complications of the surgery. However, 2 self-inflicted deaths occurred more than 1 year after the donation. Although the relationship between these 2 deaths and the donor operation is unclear, we believe these outcomes are notable because donor candidates are carefully screened for psychiatric problems and score the same or better than the general population on health status surveys.8–10 We suggest that these 2 self-inflicted deaths could have been caused by the stress associated with donation, or could reflect previously unrecognized emotional instability.
This analysis has 3 purposes: to provide a referenced source of all documented living donor deaths after LDLT; to perhaps provide a better estimate of the donor death rate associated with this procedure; and to provide an impetus for centers with knowledge of unreported deaths to submit these outcomes for review by the liver transplantation community.