Estimates of Early Death, Acute Liver Failure, and Long-term Mortality Among Live Liver Donors

Article Outline

• Abstract
• Subjects and Methods
  • Study Population
  • Outcome Ascertainment
  • Matched Live Kidney Donors
  • Matched National Health and Nutrition Examination Survey III Participants
  • Statistical Analysis
• Results
  • Characteristics of Live Liver Donors and Recipients
  • Trends in LDLT
  • Early Death
  • Catastrophic Events
  • Long-term Mortality
• Discussion
• Acknowledgments
• Supplementary material
• References
• Copyright

Background & Aims

We sought to estimate the risk of perioperative mortality or acute liver failure for live liver donors in the United States and avoid selection or ascertainment biases and sample size limitations.

Methods

We followed up 4111 live liver donors in the United States between April 1994 and March 2011 for a mean of 7.6 years; deaths were determined from the Social Security Death Master File. Survival data were compared with those from live kidney donors and healthy participants of the National Health and Nutrition Examination Survey (NHANES) III.

Results

Seven donors had early deaths (1.7 per 1000; 95% confidence interval [CI], 0.7–3.5); risk of death did not vary with age of the liver recipient (1.7 per 1000 for adults vs 1.6 per 1000 for pediatric recipients; P = .9) or portion of liver donated (2.0 per 1000 for left lateral segment, 2.8 per 1000 for left lobe, and 1.5 per 1000 for right lobe; P = .8). There were 11 catastrophic events (early deaths or acute liver failures; 2.9 per 1000; 95% CI, 1.5–5.1); similarly, risk did not vary with recipient age (3.1 per 1000 adult vs 1.6 per 1000 pediatric; P = .4) or portion of liver donated (2.0 per 1000 for left lateral segment, 2.8 per 1000 for left lobe, and 3.3 per 1000 for right lobe; P = .9). Long-term mortality of live liver donors was comparable to that of live kidney donors and NHANES participants (1.2%, 1.2%, and 1.4% at 11 years, respectively; P = .9).

Conclusions

The risk of early death among live liver donors in the United States is 1.7 per 1000 donors. Mortality of live liver donors does not differ from that of healthy, matched individuals over a mean of 7.6 years.

Keywords:  Liver Donation , Risk of Death , Complication , LDLT

Abbreviations used in this paper:  BMI, body mass index, CI, confidence interval, DDLT, deceased donor liver transplantation, LDLT, live donor liver transplantation, NHANES, National Health and Nutrition Examination Survey, OPTN, Organ Procurement and Transplantation Network, SSDMF, Social Security Death Master File

With the ever-growing organ shortage, live donor liver transplantation (LDLT) has emerged as the only lifesaving alternative to deceased donor liver transplantation (DDLT) for patients with end-stage liver disease.¹ Since the introduction of LDLT 2 decades ago,² thousands of children requiring liver transplants have benefited from left lateral segment grafts provided by live donors.³, ⁴, ⁵, ⁶ Adult-to-adult LDLT evolved from these successful experiences,⁷ initially through donation of the right lobe⁸, ⁹, ¹⁰ and increasingly in recent years through donation of the left lobe,¹¹ with dramatic growth rates across the United States and a significant impact on the quality of life and survival of thousands of patients.¹² Unfortunately, the growth of this important therapeutic modality in the past 8 years has fallen short of the initial expectations.¹³, ¹⁴

Although thousands of patients in the United States have benefited from LDLT,¹⁵, ¹⁶ there are 2 unrelated events that might explain the observed decline of LDLT in the United States. The first was the adoption of the Model for End-Stage Liver Disease (MELD)/Pediatric End-Stage Liver Disease Model (PELD) score for prioritizing wait-list patients for DDLT in February 2002.¹⁷ The second was a highly publicized donor death in January 2002, the impact of which might have “transcended individual occurrence in the wake of subsequent national and international media furor.”¹⁸ As such, one event (adoption of the Model for End-Stage Liver Disease [MELD]/Pediatric End-Stage Liver Disease Model [PELD] score) reduced the motivation for LDLT in those with the most urgent need, such as pediatric recipients,¹⁹ whereas the other (donor death) quite certainly increased the perceived risk of live donation, particularly for adult-to-adult LDLT. Since the occurrence of these events, LDLT in the United States has declined significantly.

In general, our understanding of catastrophic complications arising from live liver donation has been partly informed by the media,²⁰ case reports,²¹ and center-specific studies.¹³ Although a multicenter consortium,²² an analysis of health care registry data,²³ and a nationwide survey²⁴ have attempted to address the shortcomings in the literature, these efforts have been limited by selection and ascertainment biases, small sample size, and the lack of a generalizable denominator for accurate risk estimation. No study has formally compared the mortality risks associated with left lateral segment or left lobe donation versus right lobe donation. Many published reports describe donor morbidity at the largest LDLT centers in North America¹³, ²² and Asia,²⁵ limiting inferences on donor mortality at smaller centers that account for a significant number of the total LDLTs performed in the United States. There are no data regarding the long-term survival of live liver donors in the way that has recently been reported for kidney donors.²⁶, ²⁷ With reports of persistent physiologic sequelae following partial donor hepatectomy,²⁸, ²⁹ it is critical to better understand the long-term implications of these findings.

The goal of this study was to estimate the risk of early death and acute liver failure, to compare these risks by portion of the liver donated, and to quantify uncertainties in these estimates based on the entire cohort of live liver donors in the United States over a 17-year period. Also, to quantify any potential serious effects resulting from complications not captured by the study design, long-term mortality of liver donors was compared with healthy matched controls.

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Subjects and Methods 

Study Population 

All live liver donors in the United States between April 1, 1994, and March 31, 2011, as reported to the Organ Procurement and Transplantation Network (OPTN), were included in this study. Patients who participated in domino liver transplantation (n = 117) were excluded from this analysis.

Outcome Ascertainment 

Details of a significant early postoperative event such as early death, acute liver failure, and liver transplant were reported to the OPTN by transplant centers (per OPTN policy) for live donors recovered since October 25, 1999, and, as such, were available for analysis. In addition, ascertainment of early and late postdonation death for the entire study period was augmented by linkage to the Social Security Death Master File (SSDMF) on March 31, 2011, using the Social Security number and confirming with at least one standard identifier (first name, last name, middle initial, or date of birth) as previously reported.²⁷ Any early death identified only by SSDMF linkage was confirmed with the transplant center.

Matched Live Kidney Donors 

Live kidney donors in the United States were matched to live liver donors using iterative radius matching techniques that have been previously reported.²⁷ In brief, matching was based on year of donation, age, sex, race, education background, and body mass index (BMI) (details available in Supplementary Material). Live kidney donors undergo rigorous screening before approval for donation and were chosen as the population (for which long-term survival data were available) that would represent as closely as possible the health of live liver donors. Risks of perioperative mortality (early death) and long-term mortality in live liver donors and matched live kidney donors were compared because the risks associated with live donor nephrectomy are well characterized and might therefore serve as a useful reference.

Matched National Health and Nutrition Examination Survey III Participants 

Participants in the Third National Health and Nutrition Examination Survey (NHANES III) were matched to live liver donors, as previously reported.²⁷ In brief, matching was based on age, sex, race, education background, and BMI (details available in Supplementary Material). NHANES III was a national household survey using a complex oversampled multistage design to maximize generalizability. Medical information was obtained through home interviews, physical examination, and radiologic and laboratory test results. Of 20,024 adults in NHANES III, 17,545 (88%) were excluded because of comorbidities that might have deemed them ineligible for liver donation, based on the standards of an inclusive forum of international transplant professionals (exclusion criteria are detailed in the Supplementary Material).³⁰ Those missing information on kidney disease, diabetes, heart disease, hypertension, liver disease, asthma, frailty, and hepatitis B and C virus infection were also excluded (n = 1453). Of all the participants, 2479 without identified contraindications to liver donation remained for matching.

Statistical Analysis 

Live liver donor and live kidney donor time at risk was accrued from the date of donation. For the NHANES III cohort, time at risk was accrued from the date of enrollment into the study. Early postsurgical (3-month) death rates and catastrophic event rates were calculated per 1000 donors with 95% confidence intervals (CIs) derived using Poisson exact intervals. Differences in early postsurgical death rates or catastrophic event rates across donor characteristics and calendar periods were analyzed by using χ² tests of independence. Mortality estimates (including early deaths and late deaths) were obtained by Kaplan–Meier methods, with administrative censoring at the time of linkage to the SSDMF (for live donors) and the National Death Index (for the NHANES III cohort). Long-term death rates were compared among live liver donors, matched live kidney donors, and the NHANES III cohort using log-rank tests. All analyses were performed using Stata 11.0/MP for Linux (Stata Corp, College Station, TX). All hypothesis tests were 2 sided (α = .05).

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Results 

Characteristics of Live Liver Donors and Recipients 

Between April 1, 1994, and March 31, 2011, 4111 healthy adults in the United States had donated a portion of their liver to a biological relative (77%), a spouse (6%), or a nonspousal nonbiologically related individual (17%) (Table 1). Twenty-four percent donated a left lateral segment, 9% a left lobe, and 67% a right lobe. Among all live donors, 90% were younger than 50 years, 78% were white, and 51% were female. Although 15% were obese (BMI>30 kg/m²) and 22% had smoked cigarettes at some point, all live donors had reportedly excellent hepatic and renal function (total bilirubin, 0.6 ± 0.5 mg/dL; aspartate aminotransferase, 23.2 ± 12.0 IU/L; alanine aminotransferase, 25.9 ± 24.2 IU/L; alkaline phosphatase, 68.5 ± 30.2 mg/dL; albumin, 4.3 ± 0.6 g/dL; international normalized ratio, 1 ± 0.1; and creatinine, 0.9 ± 0.3 mg/dL).

Table 1. Live Liver Donors (April 1, 1994, to March 31, 2011)

	n (%)
Age (y)
17–29	1308(31.8)
30–39	1422(34.6)
40–49	961(23.4)
50+	420(10.2)
Sex
Female	2094(50.9)
Male	2017(49.1)
Race/ethnicity
White	3223(78.4)
Hispanic	533(13.0)
Black	234(5.7)
Asian	121(2.9)
Education
High school or less	880(35.2)
Attended college	692(27.7)
Bachelor's degree	694(27.7)
Graduate degree	236(9.4)
BMI (kg/m2)
15–24	1357(42.8)
25–29	1354(42.7)
30+	458(14.5)
Smoking (ever)
No	1256(77.9)
Yes	356(22.1)
Liver function tests, mean (SD)
Total bilirubin (mg/dL)	0.6(0.5)
Aspartate aminotransferase (IU/L)	23.2(12.0)
Alanine aminotransferase (IU/L)	25.9(24.2)
Alkaline phosphatase (mg/dL)	68.5(30.2)
Albumin (g/dL)	4.3(0.6)
International normalized ratio	1.0(0.1)
Relation to recipient
Parent	1035(25.3)
Child	1034(25.2)
Sibling	648(15.8)
Other biological	420(10.2)
Other nonbiological	713(17.4)
Spouse/partner	249(6.1)
Reported liver lobe
Left lateral segment	996(24.3)
Left lobe	359(8.8)
Right lobe	2742(66.9)

NOTE. Characteristics for age, sex, race, relation to recipient, and reported liver lobe were available throughout the study period. For race/ethnicity, 37 individuals self-reported as in other categories and were included among white subjects. Data on education were available starting October 25, 1999, and missing in 25% of cases in 2000 and thereafter; data on BMI were available starting October 25, 1999, missing in 18% between 2000 and 2004 and 11% thereafter; data on smoking were available starting in May 2005 and not missing thereafter; data on bilirubin were available starting June 3, 2004, missing in 4% in 2005 and 2% thereafter; data on aspartate aminotransferase were available starting June 30, 2004, missing in 24% in 2005 and 5% thereafter; data on alanine aminotransferase were available starting June 30, 2004, and missing in 4% thereafter; data on alkaline phosphatase were available starting June 30, 2004, missing in 6% in 2005 and 1% thereafter; data on albumin were available starting June 30, 2004, missing in 9% in 2005 and 3% thereafter; data on international normalized ratio were available starting June 30, 2004, and missing in 5% thereafter; and data on creatinine were available starting June 30, 2004, and missing in 1.5% thereafter.

Trends in LDLT 

Adult-to-child LDLT was the principal type of LDLT (174/178) practiced in the United States between 1994 and 1996, a period in which 54–64 LDLTs were performed annually at 9–17 centers. The majority of the adult-to-child procedures involved donation of the left lateral segment (154/174), whereas only a small proportion involved donation of the left lobe (20/174). Three adult-to-adult procedures are reported as having been performed during this period, and these include one left lateral segment donation and 2 left lobe donations. After 1997, along with the emergence of right lobe adult-to-adult LDLT in the United States, the number of adult-to-child LDLTs increased significantly. However, from 2001 onward, the number of adult-to-child LDLTs declined to a nadir of 50 in 2004 (Figure 1).

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• Figure 1. 

  Trends in LDLT in the United States, 1994–2010. (A) The number of LDLTs performed in the United States (1994–2010) by procedure type: left lateral segment LDLT (green), left lobe adult-to-child LDLT (lime), left lobe adult-to-adult LDLT (yellow), and right lobe adult-to-adult LDLT (orange). (B) The number of centers performing LDLT: those performing only adult-to-child LDLT (green) and those performing adult-to-adult (and/or adult-to-child) LDLT (orange). Only 3 adult-to-adult LDLTs were reported to the OPTN between 1994 and 1996, and these included one left lateral segment and 2 left lobe donations. The first published report of a right lobe adult-to-adult LDLT in the United States was of one performed in 1997,⁹ and the subsequent exponential growth in adult-to-adult LDLT is generally attributed to the expansion of this novel procedure.¹⁴

Based on published reports, the first right lobe adult-to-adult LDLT in the United States was performed in 1997. In the subsequent years, there was an exponential growth in right lobe adult-to-adult LDLT. As with adult-to-child LDLT, the number of right lobe adult-to-adult LDLTs declined significantly after 2001. Although no left lobe adult-to-adult LDLT was performed in 1997, 4 procedures were performed in 1998, 19 in 1999, and 7 in 2000. Between 2001 and 2006, no more than 11 left lobe adult-to-adult LDLT procedures were performed in a given year. Since 2007, however, an increasing number of left lobe adult-to-adult LDLTs were performed (16 in 2007, 17 in 2008, 21 in 2009, and 33 in 2010).

In general, the rise and fall of LDLT (both adult to child and adult to adult) also correlated with the number of transplant centers performing the procedure across the nation (9 in 1994, 25 in 1998, and 55 only a year later in 1999; after peaking at 68 centers in 2001, LDLT centers declined in number to 56 in 2003 and to 42 by 2009). The volume of LDLTs performed by the 42 centers in 2009 ranged from 1 to 24, with a median of 3 transplants.

Early Death 

Overall, 7 live liver donors died within the first 90 days after donation (1.7 deaths per 1000 donors; 95% CI, 0.7–3.5) (Table 2). Although this appears to be a higher rate than among matched live kidney donors (0.5 deaths per 1000 donors; 95% CI, 0.1–1.8), there was no statistically significant difference between these rates (P = .09). By contrast, as would be anticipated, live liver donors had a significantly higher risk of early death than matched NHANES III participants who likely did not undergo a surgical procedure in their first 90 days of follow-up (P = .008).

Table 2. Early Death and Acute Liver Failure After LDLT

	Early deatha			Early death or acute liver failure
	n	Rateb (95% CI)	P	N	Rateb (95% CI)	P
Cohortc
Liver donor	7	1.7(0.7–3.5)		1	2.9(1.5–5.1)
Kidney donor	2	0.5(0.1–1.8)	.09		N/A
NHANES III	0	0.0(0.0–0.9)	.008		N/A
Recipient aged
Child	2	1.6(0.2–5.8)	.9	2	1.6(0.2–5.8)	.4
Adult	5	1.7(0.6–4.1)		9	3.1(1.4–6.0)
Lobe/segment resected
Left lateral	2	2.0(0.2–7.3)	.8	2	2.0(0.3–7.8)	.9
Left lobe	1	2.8(0.1–15.5)		1	2.8(0.1–15.5)
Right lobe	4	1.5(0.4–3.7)		8	3.3(1.5–6.2)
Year of donatione
1994–1998	1	2.9(0.1–16.4)	.8	1	2.9(0.1–16.4)	1.0
1999–2002	2	1.3(0.2–4.8)		4	2.6(0.7–6.7)
2003–2010	4	1.8(0.5–4.7)		6	2.7(1.0–6.0)

Among live liver donors, the risk of an early death was comparable between adult-to-child and adult-to-adult donors (1.6 deaths per 1000 donors [95% CI, 0.2–5.8] versus 1.7 deaths per 1000 donors [95% CI, 0.6–4.1]; P = .9). Similarly, left lateral segment, left lobe, and right lobe donors had statistically comparable risks of early death (respectively: 2.0 deaths per 1000 donors [95% CI, 0.2–7.3], 2.8 deaths per 1000 donors [95% CI, 0.1–15.5], and 1.5 deaths per 1000 donors [95% CI, 0.4–3.7]; P = .8). Finally, there was no detectable change in risk of early death over time (P = .8).

There were no obvious correlates with early death throughout the study period, whether by donor age (decedents were in their 20s to 50s), recipient age, or portion of liver donated (decedents included 2 adult-to-child and 5 adult-to-adult donations, including one left lobe donor), center volume at the time of donor death (<20 to 100+ LDLTs), or cause of early death (anaphylaxis, multi-organ failure, infection, drug overdose, suicide, cardiovascular and respiratory arrest) (Table 3).

Table 3. Perioperative Mortality After Live Liver Donation (April 6, 1994, to March 31, 2011)

Donor age (y)	Recipient age (y)	Donation year	Donor no.	Donated lobe	Days to death	LDLT (%)a	LDLT no.	Cause of death
20s	Infant	1997	1	Leftlateralb	2	100	1–20	Anaphylaxisb
40s	40s	1999	2	Rightlobec	21	29	51–100	Multi-organ failurec
50s	50s	2002	3	Rightlobed	3	75	100+	Infectiond
30s	Infant	2005	4	Leftlaterale	58	91	21–50	Overdosee
30s	40s	2009	5	Leftlobe	71	99	51–100	Suicide
50s	50s	2010	6	Rightlobe	0	94	100+	Cardiovascular
30s	30s	2010	7	Rightlobe	4	100	100+	Respiratory arrest

Supplement to OPTN data:

Catastrophic Events 

A total of 11 live liver donors had catastrophic outcomes during the study period (2.9 per 1000 donors; 95% CI, 1.5–5.1). Of these events, 7 were early deaths (including one preceded by sepsis and multi-organ failure), one was subfulminant liver failure, and 3 were acute liver failure.

The risk of a catastrophic outcome was not statistically different between adult-to-child and adult-to-adult donors (1.6 per 1000 donors [95% CI, 0.2–6.2] vs 3.1 per 1000 donors [95% CI, 1.1–5.5]; P = .4). Similarly, left lateral segment donors, left lobe donors, and right lobe donors had statistically comparable risks for catastrophic outcomes (respectively: 2.0 per 1000 donors [95% CI, 0.3–7.8], 2.8 per 1000 donors [95% CI, 0.1–15.5], and 3.3 per 1000 donors [95% CI, 1.5–6.2]; P = .9). Finally, as with early death, there was no detectable difference in risk of catastrophic outcome over time (P = 1.0).

All initially nonfatal catastrophic outcomes occurred in right lobe donors (Table 4). One resulted in death secondary to sepsis and subsequent multi-organ failure. Another resulted in subfulminant liver failure and recovered without requiring DDLT. The other 3 catastrophic events among right lobe donors were rescued with prompt DDLT.

Table 4. Characteristic Features of 5 Incidences of Acute Liver Failure After Live Liver Donation

N/A, not applicable; DDLT, recipient of rescue deceased donor liver transplant.

Long-term Mortality 

Overall, 4111 live donors were followed up for a median of 7.6 years (interquartile range, 4.2–10.1) and a total of 29,965 person-years. During this period, 31 donor deaths occurred at a rate of 1.04 deaths per 1000 person-years, with 24 of these deaths beyond 90 days. Cumulative mortality estimates for live liver donors, matched live kidney donors, and NHANES III participants were very similar at 2 years (0.3%, 0.2%, and 0.3%), 5 years (0.4%, 0.4%, 0.4%), 9 years (0.9%, 1.0%, and 0.8%), and 11 years (1.2%, 1.2%, and 1.4%) (P = .9 for live liver donor versus matched live kidney donor; P = .9 for live liver donor versus NHANES III participants) (Figure 2).

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• Figure 2. 

  Kaplan–Meier curves comparing the cumulative mortality of live liver donors, matched live kidney donors, and a matched NHANES III cohort (identified among participants in NHANES III).

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Discussion 

In this national study of all live liver donors in the United States over a 17-year period, we show that the risk of death after liver donation was 1.7 per 1000 donors and the risk of catastrophic outcomes including early death and acute liver failure was 2.9 per 1000 donors. The risk of perioperative death following liver donation appeared to be 3.4-fold higher than in carefully matched live kidney donors, although this difference was not statistically significant (P = .09). Additionally, the long-term risk of mortality following liver donation (1.2% 11-year mortality) was very similar to that in matched live kidney donors (1.2% 11-year mortality) and in matched NHANES III participants (1.4% 11-year mortality).

A previous national survey had indicated that the risk of death quoted by transplantation teams to potential donors varied by more than a factor of 10, from less than 1 per 1000 to more than 10 per 1000.²⁴ This survey estimated the actual risk of catastrophic outcomes to be 4 per 1000. However, the survey was based on data collected 10 years ago, barely within 2 years of introduction of right lobe adult-to-adult LDLT to the United States, and based on only 449 adult-to-adult donors. A subsequent analysis by Trotter et al updated estimates for the risk of donor death and reported these to range from 1.5 to 2.0 deaths per 1000 donors.²⁰ However, this study pooled data from North America and Europe and relied considerably on lay literature. Citing these and other similar reports in the literature, the Vancouver forum on the care of the live organ donor quoted 1 per 1000 as the risk of mortality associated with left lateral segment donation versus 5 per 1000 for right lobe donation.³⁰ The risk of catastrophic outcomes was stated to be 4–6 per 1000 donors.

The estimates in the current analysis show no difference in the risk of early death or catastrophic outcome by portion of liver donated. We believe that these current estimates have several advantages over most prior ones. First, they are derived from a US national registry and subgroups of donors were defined by portion of liver donated. Key end points were ascertained and verified using more than one source. For death, reports by transplant centers to the OPTN (since October 1999) were supplemented by linkage to the SSDMF, and vice versa, which is crucial because donor follow-up practices may not be standard across all centers. For acute liver failure, reports to the OPTN were supplemented with data from the liver transplant waiting list. This approach addresses key limitations that arise from relying on lay literature or from any single source of information. With defined denominators and robustly ascertained outcomes, the present analysis provides more accurate and more precise estimates than previously reported and addresses key concerns identified in the literature.³¹

Although we report right lobe donors as having similar risks of catastrophic outcomes (including early death and acute liver failure) to left lateral segment and left lobe donors, all 5 donors that developed hepatic insufficiency in the perioperative period were in fact right lobe donors. One of these had multi-organ failure secondary to sepsis, with acute liver failure as a secondary diagnosis. The residual liver volume following right hepatectomy in this case was 40%.²¹ In general, the findings in the other 4 donors are also consistent with risks associated with hepatic resection because only about 25% of the liver is resected in left lateral segment donation, whereas 60% to 70% of the liver volume is removed in right lobe donation.⁸ Improved accuracy and experience with technologies for preoperative liver-graft volumetry might reduce the risk of hepatic insufficiency among right lobe donors while simultaneously ensuring appropriate graft-recipient weight ratios. For this current analysis, however, we did not have available to us any data on liver volumetry and, as such, we were not able to evaluate the association between residual liver volume and risk of acute liver failure.

Although catastrophic outcomes including early death and acute liver failure are the most adverse outcomes that a donor might develop, these are by no means the only end points necessary to understand proper informed consent. Numerous other complications do occur after live donation,²², ²⁵, ³², ³³ including intraoperative injuries, biliary leaks, biliary strictures, abscess, bowel obstruction, hepatic artery thrombosis, portal vein thrombosis, inferior vena cava thrombosis, infections, and many other complications. Although most complications following live liver donation are minor and might not require any specific form of intervention, some require pharmacologic and/or surgical intervention and can be very debilitating. Various studies, from single centers³⁴ and multicenter consortia,²² have reported these morbidity outcomes using the Clavien system of severity.³⁵ Overall, right lobe donors have been reported to experience the most frequent and most severe complications. Furthermore, there have been no observed reductions in donor morbidity with increasing center experience. Although these morbidities were not included in the current analysis, our findings indicate that, on average, including comorbidities experienced, live liver donors do not seem to have decreased longevity, at least not in a time frame covered by our study. By extension, subclinical changes that have been reported to persist among donors do not appear to be associated with decreased survival.²⁸, ²⁹

Finally, it is important to note that 5 of the 7 documented cases of early death identified in this study occurred over a 16-year period, whereas the 2 most recent donor deaths occurred within 3 months of each other and at experienced centers. Donor deaths have also been reported in other regions of the world with varying event rates (0.3 deaths per 1000 donors in Japan vs 1.7 deaths per 1000 donors in the United States vs 2.3 deaths per 1000 donors in Europe).²⁰, ³³ Because Asia is notable for its extensive experience with hepatobiliary dissection and for its heavy reliance on live donors for liver transplant,³⁶ the relatively low event rates in Japan seem to contradict the finding in this study of no correlation between center-level experience and the risk of early death. It is likely, however, that other donor-related and preoperative factors are responsible for these regional differences and that some of these factors are crucial to our understanding of the risks donors face. For these reasons, rigorous and systematic studies, the implementation of perioperative safety procedures, and renewed efforts to prevent donor deaths and other poor outcomes must continue to be high priority.

There were some limitations to this analysis. First, live liver donors who proceeded to liver donation were meticulously screened and likely more healthy than NHANES III participants. The ideal comparison group would have included healthy individuals who were cleared for donation but did not proceed to donation. However, this comparison group was not available, and instead we were able to select such individuals from NHANES III who would have been predicted to be eligible for live liver donation based on established criteria for screening donors. We also compared live liver donors with matched live kidney donors, who also undergo relatively stringent screening.

Another limitation was the small number of donors and events in the subgroup analyses. For instance, although the data suggest that left lateral segment, left lobe, and right lobe donation were associated with similar catastrophic event rates, this might partly reflect small sample size and lack of statistical power. However, given that these estimates were based on the entire population of live liver donors in the United States, they are the most accurate depiction of the mortality risks that donors face across the country. Also, some subgroups (eg, n = 1241 for pediatric recipients versus n = 2870 for adult recipients) had considerably large sample sizes, so in these cases it is unlikely that the comparisons were limited by small sample size.

In summary, live liver donors in the United States have a perioperative risk of mortality of 1.7 per 1000 donors (95% CI, 0.7–3.5). The risk of a catastrophic donor outcome (acute liver failure or early death) is estimated at 2.9 per 1000 donors (95% CI, 1.5–5.1). The risk of perioperative mortality or acute liver failure in the United States has not changed statistically during the past 17 years and does not seem to be associated with center-level experience. Although perioperative death after live liver donation is a significant risk faced by the live liver donor, all other donor-related complications not resulting in immediate death or acute liver failure do not seem to result in decreased long-term longevity. Long-term survival among live liver donors is equivalent to that among healthy matched live kidney donors and healthy matched individuals in general.

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Acknowledgments 

The authors affirm the following disclaimer: The analyses described herein are the responsibility of the authors alone and do not necessarily reflect the views or policies of the US Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the US government.

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Supplementary material 

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