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Abstract

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Donor right hepatectomy for adult-to-adult live donor liver transplantation (ALDLT) is a major surgical operation for the benefit of the recipient. Justification of procedure mandates knowledge of the possible physical and psychological negative effects on the donor. We prospectively and longitudinally quantified donor quality of life using generic and condition-specific questionnaires up to 1 year. The generic questionnaires were the Karnofsky Performance Status scale and the Chinese (Hong Kong) version of the Medical Outcomes Study 36-Item Short-Form Survey, which measures 8 health concepts: 4 physical components and 4 mental components. Within 1 year, 30 consecutive donors were included. These 11 male and 19 female donors (36.7% and 63.3%, respectively) had a median age of 35 years (range, 21-56 years). There was no donor mortality or major complications. Donor quality-of-life worsening was most significant in the first 3 postoperative months, particularly among the physical components. The physical and mental components returned to the previous levels in 6 to 12 months' time, though the Karnofsky performance scores were slightly lower at 1 year (P = 0.011). Twenty-six (86.7%) donors declared that they would donate again if there were such a need and it were technically possible. It was noticed that older donors were more likely to express unwillingness to donate again. In conclusion, the temporary worsening of donor quality of life substantiates ALDLT as an acceptable treatment modality. Liver Transpl 12:1529–1536, 2006. © 2006 AASLD.

Donor right hepatectomy in adult-to-adult live donor liver transplantation (ALDLT) is among the most major donor surgical operations performed on a human volunteer. The satisfaction of saving the life of the recipient is likely the major benefit to the donor.1 Physically the donor is subjected to risks and even harm from the organ donation. The rapid growth of ALDLT is attributable to the refractory shortage of deceased donor liver grafts and the ever-improving recipient survivals.2–4 Studies have already proved that ALDLT reduces the mortality of recipients listed for deceased donor liver transplantation.5, 6 Concerns about ALDLT stem from the magnitude of the donor procedure. This is in contrast to donor left hepatectomy in the adult-to-child live donor liver transplantation. In a provocative editorial, Russell Strong, who successfully performed the first adult-to-child live donor liver transplantation using the left lateral segment, cautioned the use of the right lobe, which is often required in ALDLT.7 His view was corroborated by the Chicago Group, which methodically developed one of the first pediatric programs.8 While the transplant community reckons that donor safety comes first,9–11 the donor procedure in ALDLT has an estimated mortality of 0.5%.12 Devastating complications of donors themselves undergoing salvage liver transplantation have also been reported.13 Apart from these incidences, about 20%14 and up to 67% of donors in one series15 developed complications. It is undeniable that temporary morbidity affects all donors both physically and psychologically.

The World Health Organization defines health as the general well-being of an individual, which is more than the mere absence of diseases and has 3 dimensions: physical, mental, and social. This definition matches very well with the health-related quality-of-life (HRQL) assessment instruments, which basically include the physical, emotional, and social domains.16 HRQL refers to how illness or its treatment affects a subject's ability to function, and its symptom burden. Kidney transplantation is often considered the pathfinder of solid organ transplantation. Live donor kidney transplantation donor HRQL studies are more well established.17, 18 However, their data could not be extrapolated to ALDLT because of the lower morbidity (<2%) and mortality (0.02%) in live donor kidney transplantation.19 In ALDLT, with few exceptions,20, 21 published donor HRQL studies are retrospective and not longitudinal.22–26

The aim of this study was to prospectively and longitudinally quantify HRQL issues of live liver donors in ALDLT. Attempts were also made to identify donors who were negatively affected and the risk factors accounting for such outcomes. This knowledge may better guide transplant professionals and future potential live liver donors in the intelligent practice of ALDLT.

PATIENTS AND METHODS

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Patients

Prospectively, we accrued 30 consecutive live liver donors from December 2002 to December 2003 (ALDLT case no. 116 to 146). One Indian female donor within the same period who did not speak Chinese and required much assistance from English interpreters during the entire donor evaluation was excluded (ALDLT case no. 137). Donor work-up began once the volunteer has decided to be evaluated as a potential live liver donor. A strategy for collecting HRQL data appropriate to all donors was implemented. Two liver transplant coordinators assisted the donors in completing the questionnaire to prevent incomplete data collection. Donor characteristics including educational level, income, marital status, family make-up, and relationship with the liver recipient were recorded.

The Karnofsky Performance Status (KPS) Scale,27 which relates to the subjects' ability to perform activities of daily living, was used to score the donors. The Chinese (Hong Kong) version of the Medical Outcomes Study 36-Item Short-Form Survey (SF-36), a validated generic multidimensional measure of HRQL outcomes was completed. The 36 questions (items) are distributed across 8 health concepts: physical functioning (10 questions), physical role (4), bodily pain (2), general health (5), vitality (4), social functioning (2), emotional role (3), mental health (5), and a single item on perceptions of health transition over the last 1 year. The typical questions take the form of “In general, would you say your health is: excellent, very good, good, fair, or poor?” For health transition, the donor is asked to rate his or her own health at present as compared with 1 year ago. The answers are: much better, somewhat better, about the same, somewhat worse, or much worse. SF-36 is a scientifically validated survey instrument designed for persons 14 years of age or older to measure overall physical and mental health status from the subject's perspective. The 36-item questionnaire can be self-administered or completed with assistance in less than 10 minutes. It has been the most widely accepted and utilized standard measure of generic health status and HRQL. The use of SF-36 has a main advantage of assessing health concepts that are not age-, disease-, or treatment-specific. SF-36 also provides a common yardstick to compare these donors with subjects suffering from other diseases, as well as normal subjects sampled from the general population.28 The resulting scores of SF-36 were transformed into a scale of 0 (worst possible score) to 100 (best possible score) per SF-36 method for analysis.29 The mean baseline score was transposed to 0, and subsequent scores were charted with reference to this baseline.

Apart from SF-36, donors were also asked to complete a condition-specific questionnaire (see Appendix), which was designed to evaluate the donor's ability to cope with major hepatic surgery. Satisfaction, values, and preferences of the donor were also looked into in a more focused manner.30 Assessment time points were set preoperatively, and then postoperatively at the end of the first, second, third, sixth and 12th months. The study was completed at 1 year for each donor.

Statistical Analysis

Values were expressed as mean and standard deviation, percentage, or median and range as appropriate. Paired sample t test with P values adjusted by the Bonferroni correction were used for continuous variables. Fisher exact test was used for categorical data analysis. The Statistical Package for the Social Sciences version 12.0 (SPSS, Inc. Chicago, IL) was used for data analysis. Only P values of less than 0.05 were considered significant.

RESULTS

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

None of the donors for ALDLT within this period were excluded from this study because of donor refusal or poor postoperative physical status, which might have hampered the completion of the questionnaires. Characteristics of the 30 donors and 30 recipients are summarized in Tables 1 and 2, respectively. Nineteen donors were first-degree relatives and 10 were the wives of the recipients. One donor abroad did not complete the questionnaire at the sixth month.

Table 1. Donor Characteristics (n = 30)
CharacteristicNumber
Gender, male:female (%)11:19 (36.7:63.3)
Age, years (range)35 (21-56)
Race 
 Chinese29
 Filipino1
Relationship to recipient 
 Child 
  Son7
  Daughter4
 Sibling 
  Sister5
  Brother3
 Second-degree relative 
  Nephew1
 Spouse 
  Wife10
Table 2. Recipient Characteristics (n = 30)
CharacteristicNumber
  • Abbreviations: HBV, hepatitis B; HCV, hepatitis C; MELD, model for end-stage liver disease; ICU, intensive care unit.

  • *

    Value expressed as median, with range in parentheses.

Gender, male:female (%)25:5 (83.3:16.7)
Age, years (range)49 (28-62)
Underlying liver disease requiring transplantation 
Cirrhosis3 (3 HBV)
Hepatocellular carcinoma9 (6 HBV, 3 HCV)
Fulminant hepatic failure2 (1 HBV, 1 autoimmune)
Cirrhosis with acute deterioration10 (10 HBV)
Chronic active hepatitis with acute flare6 (6 HBV)
Status before liver transplantation reflected by:MELD score:
 All recipients (n = 30)31 (8-46)*
 Elective (n = 12)16 (8-24)*
 Emergency (n = 18)38 (27-46)*
In hospital with complication of liver disease, n = 4 
Emergency (in ICU, not on life support), n = 4 
Emergency (in ICU, on life support), n = 10 

Donor Medical Outcomes

There was no donor mortality or major complication. Minor complications occurred in 5 donors (16.7%) (wound infection in 3, right pleural effusion in 1, and occipital pressure sore in 1). Although none of the donors received any on-going medical treatments, a high proportion of them remained symptomatic (15/30, 50%; Table 3).

Table 3. Symptoms of Donors at a Median Follow-Up of 1 Year
SymptomNumber
Wound pain6
Wound itchiness4
Malaise2
Tension around wound3
Wound numbness2
Irregular breathing1
Headache1
Stomachache1
Backache1
Loss of memory1
Eczema1
Subjective sensation of hypertension1
Sickness susceptibility1

Recipient Medical Outcomes

There was no recipient mortality. However, 11 recipients had complications (graft loss in 1, bile leakage in 1, intra-abdominal collection in 3, pleural effusion in 1, biliary stricture in 4, and portal vein stenosis in 1).

Donor Psychosocial Outcomes

At the end of the 1-year assessment period, 20 donors (66.7%) felt that recovery was complete. Prior to the donor operation, 24 were employed full-time, 3 were housewives, and 3 were unemployed. Of the 24 donors (80%) who were employed prior to donation, 22 (91.7%) returned to the same job afterward. The median time for return to work was 9 weeks. New jobs were taken up by 2 donors (8.3%). Of the 3 donors who were not employed prior to donation, 1 undertook full-time studies, and 2 took jobs.

A change of body image was perceived by 11 (36.7%) donors (weight gain in 2, scaring in 8, weight loss in 2, pallor in 2, and distorted contour of trunk in 1). Of the 28 sexually active donors, 27 (96.4%) experienced no impairment of sexual function. One expressed that she was more cautious during sexual activities. The remaining 2 donors were sexually inactive. Fifteen donors (50%) felt that their relationship with the recipient has improved. The remaining 15 (50%) reckoned that their relation remained unchanged.

The mean KPS Scale score of the donors returned to almost 100% after 6 to 12 months (Fig. 1). Nevertheless, a statistically lower KPS score was noted at 1 year (P = 0.011). The mean SF-36 scores of these donors are depicted in Figure 2. The donors experienced a substantial drop in physical abilities right after donor hepatectomy most significantly in the physical domains. Physical functioning, physical role, and bodily pain consistently improved in due course. At 6 months, there was no statistically significant worsening of physical functioning (degree of freedom = 27, P = 0.394). This outcome was similar to the scores of physical role and bodily pain at 6 months. Two of the 4 mental components (vitality and social functioning) were only moderately affected, mainly in the first postoperative month (Table 4). Figure 3 shows the mean score of donor health transition, which dropped precipitously in the first month and returned in a consistent fashion over the following 11 months. In general, the worsening of donor well-being after donor right hepatectomy revived predictably over the half-year period. Although the health transition item of the SF-36 predictably improved over 12 months, the worsening was nevertheless still perceivable at the 12th month (Fig. 3).

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Figure 1. Mean and standard deviation of Karnofsky Performance Status Scale score up to one year compared with baseline level preoperatively. *P = 0.000, **P = 0.011; statistically significant difference. Preop, before operation.

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Figure 2. Quality of life (mean and standard deviation scores) before and after donor right hepatectomy. Dotted bar denotes time prior to operation. Bar with lines slanting to the left denotes postoperative month 1. Bar with horizontal lines denotes postoperative month 2. Bar with lines slanting to the right denotes postoperative month 3. Bar with vertical lines denotes postoperative month 6. Bar with crossing lines denotes postoperative month 12.

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Table 4. SF-36 Scores of Donors Pre-Donation Until 1 Year
Time Points (n)Pre-op (30)1 Month (30)2 Months (30)3 Months (30)6 Months (29)1 Year (28)
  • Abbreviation: Pre-op, preoperatively.

  • NOTE: Values expressed as mean and standard deviation.

  • *

    Statistically significant difference.

Four physical components      
Physical functioning98.7 ± 2.364.5 ± 18.483.5 ± 12.786.5 ± 12.991.9 ± 9.295.4 ± 6.7
P value 0.000*0.000*0.001*0.3941.000
Physical role95.8 ± 9.515.8 ± 25.837.5 ± 33.351.7 ± 39.975.9 ± 33.784.8 ± 29.9
P value 0.000*0.000*0.000*0.1811.000
Bodily pain86.4 ± 16.350.5 ± 20.070.3 ± 19.068.4 ± 23.184.2 ± 15.286.3 ± 15.3
P value 0.000*0.012*0.003*1.0001.000
General health69.7 ± 17.055.2 ± 20.765.2 ± 18.065.8 ± 21.165.2 ± 19.970.2 ± 20.3
P value 0.0691.0001.0001.0001.000
Four mental components      
Vitality71.7 ± 14.854.8 ± 17.564.5 ± 15.365.8 ± 23.467.9 ± 22.368.4 ± 18.5
P value 0.011*1.0001.0001.0001.000
Social functioning84.2 ± 21.547.9 ± 24.675.0 ± 24.175.8 ± 27.684.5 ± 22.887.5 ± 18.0
P value 0.000*1.0001.0001.0001.000
Emotional role71.1 ± 37.951.1 ± 45.375.6 ± 38.174.4 ± 42.683.9 ± 34.182.1 ± 34.5
P value 0.7311.0001.0001.0001.000
Mental health72.7 ± 14.076.7 ± 15.879.2 ± 14.377.2 ± 18.976.0 ± 17.776.4 ± 15.6
P value 1.0001.0001.0001.0001.000
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Figure 3. Health transition (mean and standard deviation scores) before and after donor right hepatectomy. *P = 0.00, **P = 0.001, ***P = 0.048; statistically significant difference. PreOP, before operation; PostOp, after operation; M, month.

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Twenty-two donors (73.3%) felt that they benefited from the donation. Nonetheless, 4 donors (13.3%) expressed that they would not donate again even if there were such a need of the recipient and if it were technically possible for the donor. Their reasons are listed in Table 5. Older donors were more likely to declare not to donate again even if it were necessary. The median age of these 4 older donors was 48 years (range, 38-52 years) vs. 34.5 years (range, 21-56 years), P = 0.011). Using this question as a surrogate end-point for negative donor experience, the possible correlation with donor age, degree of emergency need for ALDLT, recipient complications, and donor complications were analyzed. Only age was found to be statistically significant (P = 0.037, Table 6).

Table 5. Reasons Expressed by Donors Who Would Not Donate Again
RelationshipAge (years)Reason
Wife52“Too old. Don't think I can tolerate such operation.”
Sister47“Suffered a lot. Maybe someone else could donate instead.”
Brother38“I am the breadwinner. I had much financial burden during the sick-leave period.”
Wife49“Lots of suffering.”
Table 6. Donors Expressed Whether They Would Donate Again in Relation to Donor Age, Degree of Emergency, Recipient Complications, and Donor Complications
 Yes (n = 26)No (n = 4)P Value
  • *

    Statistically significant difference.

Donor age: >35/≤35 years10/164/00.037*
ALDLT: elective/urgent10/162/20.531
Recipient complication(s): yes/no8/183/10.126
Donor complication(s): yes/no5/210/40.462

DISCUSSION

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Harm, though temporary, inflicted on the donor is seemingly against the tenet of medical practice of primum non nocere (first do no harm). To justify ALDLT, the 4 components of mainstream biomedical principles could be put into perspective. The benefit to the recipient, often life-saving, is obvious. Respect for donor autonomy has to be made under the premise that the donor fully understands the harm (to the donor) and benefit (to the recipient) relationship in ALDLT. Results of this study justify the acceptability of ALDLT by showing that the vast majority of donors (26/30) had a positive experience and would donate again if it were necessary and feasible. The worsening of the KPS Scale scores at 1 year, though statistically significant, was slight. For the SF-36 scores, the worsening was temporary and the donors' return to the predonation level of health occurred in a predictable manner.

In contrast to previous studies on donor HRQL, a comparison with the population norm was not performed here. As shown by the previous studies,23–25 being a preselected group, donors were universally healthier than the population norm. Even in the case when HRQL had not returned to the predonation levels, the scores were still better than the population norm. In this study, the return of the donors' HRQL to predonation levels was assessed and validated. Such analysis would not be possible or appropriate in programs with poor donor compliance to follow-up.31 The results of this study reflected the temporary nature of the donors' disabilities. Some authors have suggested a 10-points change in any SF-36 domain or more than 10% change as being clinically meaningful.32 In this regard, only physical role was worse than that before the half-year assessment. The item of health transition in SF-36 also showed a worsening at 1 year as compared to that before donation (df = 27, P = 0.048, Fig. 3). This was also true for the KPS Scale score compared with a baseline score of 100 (df = 27, P = 0.011, Fig. 1). Though a difference was demonstrable in both parameters, the actual scores were still excellent. On the other hand, the outcome of this study may also be viewed from a few perspectives.

In this study, the majority of recipients (25/30, 83.3%) were male and the majority of donors (19/30, 63.3%) were female. Among the 19 female donors, 10 were the wife of the recipient. The financial interdependence between spouses could be a driving force behind couples undergoing ALDLT. Survival of the husband, who is often the breadwinner, implies survival of the family as well. It is also worthwhile to note the zero mortality of the recipients, despite 1 graft loss. Nevertheless, adverse recipient outcomes were not shown to be associated with poor donor satisfactions in previous studies.33, 23 Is a short work-up time associated with an adverse outcome? Until now, only a minority of centers have embarked on ALDLT in the emergency situation because of the fear that the donors are not allowed sufficient time to consider the donation.34, 35 In our region, deceased donor liver grafts are scarce. Over half (18/30, 60%) of the ALDLTs in this series were undertaken as emergency operations. Under this situation, therefore, it necessitates a very short work-up time, not uncommonly less than half a day for the volunteer. In this series, there was no correlation of adverse donor experience with the emergency nature of ALDLT.

The optimal practice of ALDLT mandates, at all times, a balance between the benefit of the recipient and the risk on the donor. Recipient survival, both short-term and long-term, is a legitimate factor of concern for the donor in making the decision for donation. This most aptly applies to ALDLT in the high urgency situation when the condition of the recipient changes.36 These patients are intensive care unit–bound because of acute or chronic liver failure with life expectancy without a liver transplant of less than 7 days. The criteria are comparable to those for the United Network for Organ Sharing priority status 1 category. For potential recipients with recurrent hepatocellular carcinoma and a poor liver function, the chance of a curative liver transplantation ought to be estimated.37 This has to be interpreted with current opinions37, 38 and local results.39 Continuity of care by the same team of surgeons is logical.40 Donor feasibility has to be made in concert with the physical condition of the recipient in terms of graft size for recipients with portal hypertension.41 Such assessments are the key issues in counselling for the potential donor. From a utilitarian point of view, these data could be incorporated into the process of balancing the risks and benefits of ALDLT. On top of that, it would be useful and beneficial to the potential donors if factors that are predictors of good quality of life of donors could be identified.

It was reported in 2 series that all donors expressed they would donate again.22, 24 In this series, donors were asked if they would donate again if it were necessary, and 4 (13.3%) expressed that they would not because of the suffering and difficulties they had experienced. This percentage is higher than that in live donor kidney transplantation (4%),17 and it could be explained by the more major extent of the operation. Liver transplantation is life-saving in nature, since no long-term organ replacement therapy is available. The main purpose of kidney transplantation is, however, for the improvement of patient quality of life. In this series, recipient outcomes were generally good, with no recipient mortality. Test of correlation could be made only with donor and recipient complications. Even for larger series that may include mortality, the number will probably be small and may not allow a meaningful analysis. In our series, the 4 donors' inclination of not undergoing the same donor procedure again may not imply their regret of the decision they made initially. Having experienced such a life event, which is also an exhausting procedure, it is understandable for one to have less enthusiasm for a second donation if it were necessary and feasible. In fact, none of these 30 donors expressed that the donor experience was negative. Completion of the questionnaire at specific time points assisted by the liver transplant coordinators ensured high return rate (Table 7). However, this might introduce potential bias of the donors providing responses that they thought they were expected to provide.

Table 7. Condition-Related Questions
Post-operation: 1 month/2 months/3 months/6 months/1 year
Are you back to work/school/housework/regular activities?  Yes/No
If Yes, how soon after surgery?
Liver donation presented:
No or little financial burden
Moderate financial burden
Extreme financial burden
Was there any adverse effect on sexual functions?  Yes/No
Do you find yourself less attractive than before surgery?  Yes/No
Is your wound uncomfortable?  Yes/No
Is your wound painful?  Yes/No
Is your wound ugly?  Yes/No
In your opinion, did the recipient have a good outcome?  Yes/No
What is your ongoing relationship with the recipient? (tick one)
Same
Better
Worse
Has the surgery disrupted your family, work, or social relationships?  Yes/No
If yes, in what way?_______
Has the surgery caused you financial hardship?  Yes/No
Do you regret the decision to donate?  Yes/No
The overall donor experience was:
Not stressful
Stressful
Very stressful
Extremely stressful
Was there donor death?  Y/No
Were there donor complications?  Y/No
If yes, the details are:_______
Please make any additional comments:_______

In conclusion, donor right hepatectomy including the middle hepatic vein in ALDLT is an acceptable procedure. This fact is established on the grounds that a careful and comprehensive work-up of the donor is made, together with sound recipient results. The donor should be provided with more accurate and the most up-to-date information on the success of the recipient operation in practice and the risk to be incurred in the donor operation. Recovery of the donor is most prompt for mental domains. Physical recovery takes 6 to 12 months to complete. This long time interval to return to normalcy is required even in adult-to-pediatric LDLT.42 Nevertheless, HRQL is not compromised after full recovery. We are committed to continue documenting from live volunteers the risks associated with liver donation. We believe that the benefits of live liver donation outweigh the risks, and that ALDLT is justifiable until the supply of deceased donor liver grafts improves significantly.

REFERENCES

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES