Experience after the evaluation of 700 potential donors for living donor liver transplantation in a single center

Authors


Abstract

Adequate selection of donors is a major prerequisite for living donor liver transplantation (LDLT). Few centers report on the entire number of potential donors considered or rejected for living donation. From April 1998 to July 2003, a total of 111 living donor liver transplantations were performed at our institution, with 622 potential donors for 297 adult recipients and 78 potential donors for 52 pediatric recipients evaluated. In the adult group, only 89 (14%) potential donors were considered suitable, with a total of 533 (86%) potential donors rejected. Of these, 67% were excluded either at initial screening or during the first and second steps of the evaluation procedure. In 31% of all cases, the evaluation of donors was canceled because of recipient issues. In the pediatric group, 22 (28%) donors were selected, with the other 56 (72%) rejected. Costs of the complete evaluation process accounted for 4,589 Euro (€) per donor. The evaluation of a potential living donor is a complex and expensive process. We present the results on the evaluation of the largest group of potential donors for adults reported in the literature. Only 14% of potential donors in our series were considered suitable candidates. It has not yet been established who should cover the expenses of the evaluation of all rejected donors. In conclusion, all efforts should be made in order to develop an effective screening protocol for the evaluation of donors with the aim of saving time and resources for a liver transplantation program. (Liver Transpl 2004;10:1087–1096.)

One of the most important problems facing the transplant community is the growing discrepancy between the number of patients listed for liver transplantation and the availability of donor organs. As a result, the median waiting time for transplantation and the number of patients that die awaiting a donor liver increases every year. This situation has led to an increasing number of transplant teams pursuing an interest in the use of living donors for adult liver transplantation as a way to cope with the shortage of cadaveric organs from cadaver sources.

The application of living donor liver transplantation (LDLT) is associated with several theoretical advantages for the recipient: transplantation can be performed electively before serious decompensation in the recipient occurs, complications associated with organ preservation are minimized, and grafts of optimal quality are provided.1, 2 Additionally, LDLT offers the possibility of liver replacement to selected patients who may be ineligible for cadaveric organ transplantation.3 The drawback of this technique is the potential risk of death or serious complications in the donor and a greater incidence of technical complications in recipients. Ethical concerns have subsequently arisen and the success of this procedure will depend ultimately on 2 critical issues: donor morbidity and mortality should be reduced to a minimum and graft and recipient survival should be similar to that of conventional liver transplantation.4–6 Therefore, an adequate and thoughtful selection of donors is a major prerequisite for LDLT. Exhaustive medical and psychological evaluation and a precise anatomical study of the liver should be performed in order to guarantee the safety of the donor and provide good results for the recipient.

Most reports in the literature have focused on the evaluation protocol, morbidity, and mortality in donors or the ethical aspects of living donation. The majority of reports concerning the results of the evaluation of living donors present data of only pediatric or both adult and pediatric LDLT together.7–12 However, these data may not be directly applicable to adult LDLT (ALDLT). Some other reports have been recently published about the evaluation of potential donors for ALDLT.1, 13–17 Though the evaluation protocols are similar, the population of donors considered differs significantly in most centers: some series include only individuals who qualify for donation, but not those who were rejected on the initial screening. In other series, donors whose evaluation was canceled because of recipient issues were also excluded. Thus, while it is difficult to compare the results presented in those reports and comprehensive data about the real number of potential donors evaluated, reasons for rejection and costs of the evaluation procedure in centers performing ALDLT are still missing.

We present our experience with the development of an evaluation protocol for potential donors for ALDLT, which was adapted from our pediatric protocol. Specific criteria for the selection of donors are suggested, and the costs of the evaluation procedure are also analyzed. Results after the evaluation of a large pool of donors for ALDLT (including all screened and evaluated donors) are presented in detail and compared to the ones reported in the literature by other centers.

Abbreviations:

LDLT, living donor liver transplantation; ALDLT, adult living donor liver transplantation; €, Euro.

Patients and Methods

The policy of our program is to present the possibility of LDLT to all potential adult recipients at the time of evaluation for liver transplantation. In our pediatric program, parents are informed about this alternative. Donors should share either a genetic or significant emotional relationship with the recipient. A first interview with the potential donor(s) and the recipient is always performed by a transplant physician. This colloquium is important to inform the parties about the details of the surgery, postoperative care, complications, and reported outcomes associated with ALDLT. During this session, the initial screening of potential donors is performed. Exclusion criteria for donors include being under 18 years of age, obesity (body mass index >30 kg/m2) and medical comorbidity. The first step of the evaluation (Table 1) is performed for candidates considered initially suitable. The process of evaluation of donors can run parallel to the evaluation of the recipient, sometimes performed once the recipient has been fully evaluated. For patients with extended oncologic indications, the identification of a live donor is a prerequisite before proceeding with the recipient evaluation.

Table 1. Evaluation Protocol for Potential Living Liver Donors
  1. Abbreviations: HIV, human immunodeficiency virus; CMV, cytomegalovirus; HSV, herpes simplex virus; EBV, Epstein-Barr virus; CT, computed tomography; ECG, electrocardiogram; TSH, thyroid-stimulating hormone; T3, triiodothyronin; T4, thyroxin; CEA, carcinoembryonic antigen; AFP, alpha-fetoprotein; APCR, activated protein C resistance.

Step 1Clinical evaluation: history and physical examination
 Lab tests: blood group, hematological tests, chemistry, coagulation profile, C-reactive protein, and pregnancy test
 Serology: hepatitis A, B and C, HIV, CMV, HSV, EBV
 First informed consent
Step 2Imaging studies: “all in one” CT scan
 Histology: liver biopsy
 First psychological evaluation
 Hepatitis B vaccination (1° doses)
Step 3Special studies: ECG, chest x-ray, pulmonary function test, echocardiography, stress test
 Laboratory: thyroid function tests (TSH, T3, T4), immunoglobulines IgA, IgG, IgM, iron, transferrin, ferritin, α-1-antitrypsin, ceruloplasmin, tumor markers (CEA, AFP, Ca19-9), factors V, VII and VIII, protein C and S, APCR, and urine sediment
 Liver function tests: galactose, indocyanine, lidocaine
 First autologous blood donation
 Selected consultations
Step 4Second psychological evaluation (donor and recipient together)
 Hepatologist consultation
 Second autologous blood donation
Step 5HLA typing, cross-match
 Hepatitis B vaccination (2° doses)
 Anesthesiological consultation
 Ethical board evaluation
 Final informed consent

The protocol for evaluation of donors for ALDLT includes 5 steps (Table 1).

Step 1

The first step in the evaluation consists of a medical work-up. Blood group identity is the optimal condition, but compatibility is also accepted. We consider positive serology for hepatitis C an absolute contraindication for living donation, even in the case of a recipient with hepatitis C cirrhosis. Donors with positive core antibody for hepatitis B were initially rejected, but at present are considered for hepatitis B infected recipients. These donors should have normal liver enzymes, normal liver histology and negative hepatitis B virus in serum and in the liver detected by quantitative polymerase chain reaction assay with the Amplicor HBV Monitor test (Roche Diagnostic Systems, Grenzach-Wyhlen, Germany). This test is a standardized assay for quantifying hepatitis B virus viremia levels in the range from 102 to 107 copies/mL.

Step 2

Examinations performed in this phase evaluate the volumetry, anatomy and quality of the graft. Computed tomography scan was used for the first series of donors and seemed to be sufficiently accurate to estimate the volume of the graft. Additionally, a celiac angiography was performed to define the vascular anatomy. Since November 1999, magnetic resonance imaging has been implemented as a standard technique in our program. Initially, this exam was still supplemented with the performance use of a celiac angiography. Since November 2000, simultaneous performance use of magnetic resonance angiography reliably defined the vascular anatomy, eliminating the use of the angiography. Nevertheless, a good definition of the arterial blood supply and the anatomy of the biliary tract were not achieved until the introduction of the “all-in-one” protocol with multidetector row computed tomography scan in May 2001 (Fig. 1). The protocol includes acquisition of 3 subsequent scans after the intravenous administration of both a biliary contrast agent and a conventional iodinated contrast agent. This technique allows a detailed analysis of the vascular and biliary anatomy and accurate measurement of the total volume of the liver and the graft volume. Results obtained with the use of this technique showed a good correlation between the radiological and intraoperative findings.18, 19 We consider a graft-to-recipient body weight ratio >.8% a safe lower limit for adults, with a maximal percentage of resection in the donor liver of 60 to 65%. The ratio between residual liver volume and the donor's weight is also calculated, and a ratio of .8% is considered as a safe lower limit.

Figure 1.

Three-dimensional computed tomography arteriogram and cholangiogram obtained with the “all-in-one” protocol. The protocol includes acquisition of three subsequent scans (cholangiogram, arteriogram, and portal-hepatic venous phases) after the intravenous administration of both a biliary contrast agent and a conventional iodinated contrast agent.

Liver biopsy was initially performed only in case of marginal percentage of resection (resection of ≥60% of liver tissue) or when findings that might indicate pathologic liver conditions were disclosed in advance. After the loss of a donor due to congenital lipodystrophy not diagnosed preoperatively, a liver biopsy became a mandatory part of the evaluation. In donors for children liver biopsy is only performed in selected cases. We consider a 20% or more degree of steatosis as an absolute contraindication for donation. In case of rates between 10 and 20% we recommend diet and the performance of a second biopsy after weight reduction. Results of 10% or less of fat infiltration are accepted when the percentage of resection of the donor liver is less than 50%.

In the psychosomatic evaluation, there are two relevant aspects: one is the psychological stability of the potential donor and the second is the verification of informed consent. In case of donors for ALDLT, this evaluation is performed twice, first for the donor and in a second session for both donor and recipient together.

Step 3

During this phase, an assessment of the general operative risk is performed, including a pulmonary function test, echocardiography, and stress test. Laboratory tests are also performed (Table 1). Additional tests deemed necessary are obtained on a selective basis (e.g., colonoscopy, mammography) depending on the individual donor. The first autologous blood donation also takes place in this phase. In donors for ALDLT, we consider 2 units of autologous blood sufficient. In the case of donation for pediatric recipients, this does not seem to be mandatory. In order to perform the liver function test, potential donors are admitted to the hospital for 1 day.

Step 4

At the beginning of our experience, celiac angiography was performed during this step, but this has now been practically abandoned after the introduction of the “all-in-one” computed tomography scan. In this phase, the second autologous blood donation, the second psychological assessment in donors for ALDLT, and the consultation by our hepatologist are performed.

Step 5

German transplantation law establishes that living donors should be first or second degree relatives of recipients or should have close emotional ties with them. This condition, and the absence of any financial interest for donation, are evaluated by the ethical board, which was created in Germany after the first cases of ALDLT were performed, completely independent of the hospital evaluation team. It meets once or twice per month; however, an extra session can be called for urgent cases (i.e., fulminant hepatic failure) within 24 hours. The consultation by the anesthesiologist and the final consent from both donor and recipient are also obtained in this phase. Donors who are not native Germans are required to provide an independent translator for the consent procedures.

For the complete evaluation, candidates are scheduled for 4 to 5 appointments in the outpatient clinic and 1-day admission to perform the liver function test. Liver biopsy is also performed in the outpatient clinic, including a 3-hour period for observation after the procedure. We do not proceed in the donors evaluation process until acceptable findings are confirmed in the previous step. Potential donors are explicitly informed that they can withdraw their consent at any time. Decisions of donors to abort the donation process are kept confidential and are ascribed to medical or anatomical constraints. Once the donor evaluation is completed, both donor and recipient are presented at the interdisciplinary transplantation conference and either approved or rejected for LDLT. If they are deemed appropriate for LDLT, transplantation is scheduled.

In the case of patients with fulminant hepatic failure we perform a “quick” evaluation of the potential donor, including blood tests, electrocardiogram, chest x-ray, pulmonary function test, echocardiography, imaging study of the liver with “all-in-one” computed tomography scan, psychological assessment, and evaluation by the ethical board. The evaluation can be completed in a 24- to 48-hour time period.

Results

From April 1998 to July 2003, a total of 111 living donor liver transplantations were performed at our institution (89 cases involving a right lobe, 3 with a left lobe, and 19 cases with a left lateral lobe). In this period, a total of 700 potential living donors were considered for 349 recipients. We included in this series not only the donors who were evaluated following the stepwise procedure but also the ones who were rejected after an initial screening (through an interview with the transplant physician) and the ones whose evaluation was canceled for recipient issues. Potential donors were divided into 2 groups: Group A included donors for adult recipients, and group B consisted of donors for pediatric patients.

Group A

This group included 622 potential donors for 297 recipients (Table 2). Only 89 (14%) were suitable for living donation, with a total of 533 (86%) potential donors rejected. Out of these, 104 (20%) were refused on initial screening, 265 (49%) were rejected during the evaluation and in 164 (31%) cases the evaluation was canceled because of recipient-related reasons (Table 3 and 4).

Table 2. Demographics of Donors and Relationship With Recipients
 Group AGroup B
Total potential donors62278
 Gender (M/F)340/ 28239/ 39
 Age (yr)37 ± 11 (17–75)35 ± 6 (22–59)
Relation  
 Offspring231 (38%)1 (1%)
 Siblings127 (20%)0 (0%)
 Parents52 (8%)73 (94%)
 2nd degree51 (8%)3 (4%)
 Spouse86 (14%)0 (0%)
 Unrelated75 (12%)1 (1%)
Table 3. Global Results of Evaluated Donors
 Group AGroup BTotal
Total potential donors62278700
Potential recipients29752349
Ratio2.11.52
Accepted89 (14%)22 (28%)111 (16%)
Excluded533 (86%)56 (72%)589 (84%)
Table 4. Global Results of Rejected Donors
 Group AGroup B
Initial screening104 (20%)5 (9%)
Step 1112 (21%)20 (36%)
Step 2139 (26%)7 (12%)
Step 39 (1%)5 (9%)
Step 45 (1%)0 (0%)
Excluded for recipient-related reasons164 (31%)19 (34%)

On initial screening, most of the donors were excluded for obesity (body mass index >30 kg/m2), documented previous illness, or the presence of more than 2 risk factors (e.g., age, nicotine abuse, alcohol abuse, hypertension). These potential donors were considered unsuitable after the first interview with the transplant physician. No further medical tests were performed.

A total of 265 potential donors presented a contraindication for donation during the evaluation and were consequently excluded. Of these, 12 (42%) donors were excluded in the first step, with incompatible blood group or positive hepatitis serology being the most frequent reasons for rejection.

A total of 139 (53%) donors were rejected in the second step. Of these, 82 donors were excluded due to inappropriate liver volumetry. The most frequent reason (70 cases) was a small remnant liver for the donor (residual liver volume to donor body weight ratio <.8). In 5 cases, both graft and remnant liver were insufficient. A total of 5 donors were excluded because of alternative donors with more suitable volumetric findings. In only 2 cases was the reason for rejection a “small for size” graft for the recipient (graft-to-recipient body weight ratio <.8).

In 22 potential donors, the reason for exclusion was a pathological histology of the liver: 14 cases of steatosis degree >20%, 4 cases of hepatitis, 2 cases of hemochromatosis, 1 case of schistosomiasis in a donor originating from Egypt, and another 1 with liver fibrosis.

Only 2 potential donors were rejected because of vascular or biliary anatomical variations of the liver: in 1 case (Fig. 2) the donor presented the combination of an accessory right hepatic artery arising from the aorta, 2 left hepatic arteries, portal vein trifurcation, accessory hepatic vein from segment 8 draining in the middle hepatic vein, direct biliary drainage from segment 7 in the common bile duct, and a bile duct from segment 4 draining in the right hepatic duct. In the other case, the presence of 2 left hepatic arteries, an accessory hepatic vein from segment 8 draining in the middle hepatic vein, a portal vein trifurcation, a trifurcation of the bile duct, and a bile duct from segment 4 draining in the right hepatic duct were documented. The vascular and biliary anatomy of these donors was considered as factors for potentially high risks and complications during surgery, and the candidates were rejected.

Figure 2.

Three-dimensional computed tomography arteriogram and cholangiogram of a donor rejected because of vascular and biliary anatomical variations. In this case, the donor presented the combination of 2 left hepatic arteries, a trifurcation of the bile duct, and a bile duct from segment 4 draining in the right hepatic duct.

A total of 26 donors were rejected after psychological assessment. Of these, 21 were already excluded after the first consultation. A total of 5 potential donors, who showed persistent ambivalence after the second psychological consultation during step 4, were also excluded.

A total of 9 (3%) potential donors were rejected during the third step of the evaluation. A total of 6 cases were because of documented medical comorbidities: 3 of them involving cardiological problems (1 donor received a coronary bypass operation), 1 because of a lung carcinoma, 1 case of diabetes, and another due to abnormalities on the coagulation tests. All those morbidities were first diagnosed at the time of evaluation.

In 164 (31%) cases the evaluation of donors was canceled because of recipient issues (Table 5).

Table 5. Donors Rejected for Recipient-Related Reasons (Recipients Between Parenthesis)
 Group AGroup B
  1. Abbreviations: LT, liver transplantation; FHF, fulminant hepatic failure.

Donors rejected (no. recipients)164 (101)19 (18)
Recipient reasons  
 Exitus60 (37)1 (1)
 Tumor stage40 (20)1 (1)
 Medical comorbidity27 (17)0
 Cadaveric LT20 (15)15 (14)
 Fear of recipient13 (8)0
 Resectable tumor3 (3)2 (2)
 Recovery after FHF1 (1)0

Group B

A total of 78 potential donors were considered for 52 pediatric recipients. Demographics of the donors and results of the evaluation are shown in Tables 2, 3, and 4. A total of 22 (28%) donors were suitable for performing LDLT, the other 56 (72%) were rejected. Of these, 5 (9%) donors were rejected on initial screening. A total of 32 (57%) donors were rejected during the evaluation, most of them in the first step, as their blood group was incompatible or a positive virus serology was detected. In 19 (34%) cases, the evaluation of the donor was canceled for recipient-related reasons (Table 5).

Fulminant Hepatic Failure

From April 1998 to July 2003, a total of 71 patients who were intensive care unit–bound because of fulminant hepatic failure were put on a high-urgency list for liver transplantation in our institution. In 55 (77%) patients, no family member volunteered as a living donor: 15 died awaiting donor organs and 40 received a cadaveric graft. A total of 16 (23%) patients (11 in group A and 5 in group B) had 40 candidates who volunteered as living donors. Before the evaluation of the potential donors was completed, 5 patients received a cadaveric transplantation and 3 patients died. LDLT could not be performed in 5 patients because of withdrawal of the donor. Of these 5 patients, 2 died and the other 3 received a cadaveric graft. One patient with liver failure due to a syndrome including hemolysis, elevated liver enzymes, and low platelet counts improved rapidly without transplantation. LDLT was performed in 2 cases: a child with fulminant hepatic failure of unknown etiology and a 17-year-old patient with acute Morbus Wilson who received a right lobe from her mother.

For those patients who received a cadaveric graft, mean time from listing by Eurotransplant to transplantation was 2.6 days.

Complications during the Evaluation Procedure

A total of 116 liver biopsies were performed in donors in group A and 6 in group B. Complications were observed in 2 cases (1.6%). One donor developed a subcapsular hematoma in the right liver lobe, which was treated conservatively; however it required blood transfusion. After 7 months, the hematoma was resolved and the donor was reconsidered for ALDLT. During this time, the recipient was still waiting for a cadaveric graft and unfortunately died before the transplantation could be performed. Another potential donor also developed a subcapsular hematoma with hemobilia, requiring blood transfusion and the performance of an endoscopic retrograde cholangiography with papillotomy. The recipient in this case, diagnosed with primary biliary cirrhosis and hepatocellular carcinoma, died 5 months later. No complications were observed in donors related to the performance of celiac angiography.

Costs of the Evaluation

We analyzed the costs of the examinations performed in every step of the evaluation procedure: costs of step 1 were 567 € (Euro), for step 2 794 €, step 3 accounted for 1,462 €, step 4 for 185 € (costs of celiac angiography were not included) and step 5 for 1,581 €. Costs of the complete evaluation procedure were 4,589 €. Professional fees were not included, which would increase the costs significantly. The cost of the evaluation of all “failed donors” must be accounted for in a cost analysis of LDLT. We divided the sum of all costs associated with donor evaluations, including “failed donors,” by the total number of LDLT recipients. This number reflects the “donor acquisition fee,” which accounted for 10,619 € in the adult group and 8,644 € in the pediatric group. The “costs per recipient” reflect the sum of all costs of the evaluation of potential donors divided by the total number of potential recipients (Table 6). Costs of the evaluation of donors, hospital admission, surgical procedure, and follow-up examinations are covered by the insurance company of the recipient when LDLT is performed. It is not yet definitively established who should cover the expenses of the evaluation of all rejected donors or donors whose evaluation was canceled because of recipient issues.

Table 6. Costs (€) of the Evaluation Program for LDLT
DonorsAdultCosts (€)PediatricCosts (€)
Rejected on initial screening10410,4005500
Rejected during evaluation265293,1303234,982
Rejected for recipients reasons164233,1721953,746
Total donors rejected533536,7025689,228
Total donors accepted89408,42122100,958
Total 945,123 190,186
Costs per recipient 3,182 3,657
Costs per LDLT-donor acquisition fee 10,619 8,644

Outcome of Potential Recipients Evaluated for LDLT

A total of 349 potential recipients were considered for LDLT. A total of 107 (36%) adult and 12 (23%) pediatric patients were not able to find a suitable donor. A total of 101 (34%) patients in the adult group and 18 (35%) in the pediatric group were excluded for recipient issues. LDLT was performed in 89 (30%) adult and 22 (42%) pediatric recipients.

Discussion

Living donors undergo some degree of suffering without the compensation of a direct therapeutic benefit. For ethical reasons, adequate and thoughtful selection of donors is a major prerequisite for LDLT. The main goal of the evaluation process is to assure the safety of the donor and to provide better quality grafts for the recipients. This can only be achieved by first, an exhaustive medical and psychological evaluation of the donor and second, a precise study of the size, anatomy, and quality of the liver graft.

In the initial experience with ALDLT, most centers simply adopted the evaluation protocols used for pediatric LDLT. In time, the remarkable differences in the evaluation of donors for adult and pediatric recipients became obvious: first, the operation consists of a larger resection with potentially higher risk for the donor. Second, most pediatric donor candidates are young, healthy parents, whereas adult-to-adult donor candidates cover a wide age range (range in our series was 17–75 years) and are usually at higher risk of presenting medical problems. Finally, there is a larger number of potential donors (ratio between number of donors and recipients was 2.2 for adults and 1.5 for children in our series) and they are mostly professionals, whose time schedule is limited and psychological motivation and relationship with the donor is also quite different compared to the pediatric program (26% nonrelated donors in our adult group, 1% in our pediatric group). That means there is a need for more precise anatomical information, more exhaustive medical work-up, and a more refined psychological evaluation in ALDLT. Modifications introduced in the selection protocols have already been well described by most centers. The process of evaluation of donors starts with an initial screening, which in some centers is performed through a brief telephone interview conducted by a transplant coordinator. This screening sometimes includes the assessment of liver function and blood group by the primary care physician. The evaluation itself is a stepwise procedure, consisting of a series of blood tests and cardiopulmonary and radiological examinations, combined with an intensive interaction between donor and transplant staff (including hepatologists, surgeons, anesthesiologists, and psychiatrists). The Achilles heel in the evaluation of donors is definitively the assessment of the anatomy and quality of the graft, and different reports1, 2, 17, 20, 21 have confirmed that there is still a great deal of variability among centers, mainly regarding mainly 3 diagnostic studies: liver biopsy, hepatic angiography, and cholangiography.

Most reports in the literature have been focused on a description of the evaluation protocol, but comprehensive data about the total number of donors evaluated, reasons for rejection, or costs of the evaluation procedure are still missing. Initial reports were made on the evaluation of donors for LDLT in children.7–12 However, this data may not be directly applicable to ALDLT due to the vastly different surgical procedure and the diversity of potential donors. Trotter et al.13 published the first detailed report on the outcome of potential recipients and donors evaluated for ALDLT. Only 3 other groups have recently reported their experience on the evaluation of candidates for ALDLT.1, 15, 16

We show the results of the selection process of all potential donors for LDLT. Comparison between our results and the ones previously published is difficult because of the lack of uniform criteria on the presentation of the data.

In our study, 86% of potential donors for ALDLT were rejected; Pomfret et al.16 and Pascher et al.15 reported a lower rejection rate of 69%, but donors rejected on initial screening were not included. Trotter et al.13 reported a significantly lower rejection rate of 35%, but donors excluded for recipient-reasons and donors excluded on initial screening were not considered.

In the pediatric group in our series, 72% of donors were rejected, which represents a significantly higher rate compared with other pediatric series: 29% by Sterneck et al.10; 28% by Hashikura et al.7; 11% by Morimoto et al.8; and 57% by Baker et al.11 The difference can be explained because most of the candidates were referred to these centers after a previous selection process.

The reality is that with an increasing number of potential candidates being evaluated and a more stringent selection criteria, the evaluation of donors for ALDLT has become a costly, labor-intensive, and time-consuming procedure. In Germany, the costs of the evaluation, hospital admission, surgical procedure, and follow-up examinations of donors are paid by the recipient's insurance when LDLT is performed. The costs of evaluation of potential donors who are rejected for any reason during selection are neither covered by donor's nor by the recipient's insurance. In these cases, the hospital budget is burdened with high expenses (Table 6).

The sequence of the examinations performed during the evaluation procedure is typically based on a progression from least to most invasive, but the key factor is also to determine which examinations identify a higher proportion of unsuitable candidates. Consequently, a person with no real chance of donation could be excluded as soon as possible during the selection process, saving considerable time and expenses for the LDLT program. In our series, 67% of donors in the adult group and 64% in the pediatric group were rejected on initial screening and during the first and second steps of the evaluation. The costs of initial screening are minimal, since no medical tests are performed. Costs of examinations performed during the first and second steps of the evaluation are 566 € and 793 €, respectively, being the most expensive procedures included in the final steps of the selection (1,427 € for step 3 and 1,579 € for step 5). Thus, our evaluation protocol is effective in detecting a high percentage of unsuitable donors early in the evaluation process, saving substantial time and resources. A very important issue is the flexibility of the evaluation protocol, which should always be adapted to the characteristics of the donor (i.e., for a nonrelated donor, the psychosomatic evaluation has priority over the other examinations, for a donor older than 60 years of age, the cardiopulmonary evaluation takes place before the liver biopsy).

In our center, patients with extended indications are also considered candidates for LDLT. For this reason, we found a lower rejection rate of potential recipients (34% in the adult and 35% in the pediatric group) when compared with other series (51% by Trotter et al.13). For these patients, the identification of a living donor is a prerequisite to proceed with the recipient evaluation. This results in a large population of donors who are excluded for recipient contraindications: 31% in the adult group and 34% in the pediatric group. The costs of the evaluation of this group of donors represent one-half of the costs of all rejected donors in our program (Table 6). In order to cut the costs, we would recommend not to proceed with the evaluation of donors until the suitability of those potentially critical recipients is established.

In the pediatric group, most of the potential donors were excluded on the first step, whereas in the adult group, a similar proportion of donors were rejected during steps 1 and 2. That means once we have a suitable medical and blood group donor, the volume of the left lateral graft is almost always adequate for a pediatric recipient. Inadequate liver volume was one of the main reasons for exclusion in the adult group (31% of evaluated donors). We observed that the volume of the right graft is mostly suitable for an adult patient; however a high percentage of resection and / or a low residual liver volume (residual liver volume to donor body weight ratio <.8) in the donor was the most frequent reason for rejection. No similar data have been reported: in the series of Pascher et al.15 and Trotter et al.,13 no donor was rejected because of inadequate liver volumetry; by Marcos,1 this rate was 3%; only in the series of Pomfret et al.16 were 19.5% of donors excluded for this reason. We consider this relevant data in order to avoid a “small for size” residual liver in the donor.

A total of 8% of potential donors evaluated in our adult group were rejected because of abnormal liver biopsy. In 16 out of 26 donors, Pascher et al.15 found a steatosis >10%; Marcos1 and Pomfret et al.16 also report relatively high rates (17 and 22%, respectively) of donors rejected for the same reason. Liver biopsy is not routinely performed in all centers for the evaluation of donors, but an estimation of steatosis of the liver seems to be essential in the selection process.1, 22 Clinical, imaging, and biochemical parameters do not seem to be accurate enough to judge the extent of hepatic steatosis.23 We observed serious complications in 2 donors (1.6%) related to a liver biopsy; however, we still consider this risk to be low, taking into account that an important proportion of donors are rejected for abnormal histological findings. After the loss of a donor due to congenital lipodystrophy not diagnosed preoperatively, a liver biopsy is performed routinely in all potential donors for adult patients in our center.

Preoperative imaging studies should be able to accurately detect most anatomical variations of the donor liver, which enables preparation and may aid the surgical dissection. In very few cases, however, variations of the vascular or biliary anatomy represent a contraindication for donation in our series (2%) and in the ones reported by other authors (1% by Marcos1 and 4% by Pascher et al.15).

The relationship between donor and recipient and, consequently, the psychological motivation of potential donors, is quite different in adult versus pediatric LDLT, implicating special considerations during the selection process. In the adult group, 10% of donors were rejected after the first or second psychological assessment, with only one nonrelated donor excluded in the pediatric group (in this case no significant emotional relationship with the recipient was found). In the report of Pascher et al.15 psychological contraindications were the second most frequent cause of rejection of donors (7 out of 26). In the series of Marcos1 and Pomfret et al.,16 lower rates were reported (2 and 2.4%, respectively). The most important aspect is to establish a process of fully informed consent to protect the donor.24 The informational process starts in our center at the first interview between donor, recipient, and the physician responsible for the evaluation of donors. At this time, complete information is provided, with details about the evaluation process, surgery, complications, and outcomes, for donors and recipients, including the possible impact of donation on work and finances. Furthermore, a booklet with extensive information on LDLT is also provided. It cannot be ruled out that the physician may be “priming” the potential donors and in a way even manipulating them. To avoid this, the candidates are asked not to respond immediately but rather to think for some time before making the decision. Another question is to what extent patients understand the information provided and if they are aware of the risks and benefits of the procedure. In this sense, the role of the psychiatrist is essential, evaluating the “competence of the donors to make a decision” and finding out whether this decision was made voluntarily or whether it was influenced by any kind of internal or external coercion.25, 26

In our study, 30% of the potential transplant recipients in the adult group and 42% in the pediatric group found a suitable donor. Trotter et al.13 also reported a 30% rate and Brown et al.20 46%, both in ALDLT. The percentage of recipients with suitable donors in reports from pediatric series7, 10, 11 was higher, varying between 50 and 85%. As previously mentioned, patients were referred specifically for LDLT at these centers; in addition, screening criteria for pediatric LDLT are less stringent than for right-lobe donation. Data on the percentage of patients with suitable donors are not comparable with the ones from countries without brain-death laws. Also, differences in values, ideals, religious beliefs, and family structure vary across ethnic groups and these differences may also explain variations in the donation rates.27

Emergency adult-to-adult living donor liver transplantation for fulminant hepatic failure raises serious ethical, medical, logistic, and economic concerns. It has been strongly criticized that the evaluation in this emergency situation places the donor in a very compromising medical and psychological situation.28–30 In our experience, there was excellent cooperation between departments and personnel, making it possible to gather all needed tests and information from donors within 24 hours. Lack of voluntarism from family members (only 23% of patients had potential living donors) and the high rate of rejection of donors were the main reasons that limited the applicability of emergency LDLT in our program. A high mortality rate pretransplantation was observed, even though the average time to receive a cadaveric organ was 2.6 days.

In summary, an adequate and thoughtful selection of donors is a major prerequisite for LDLT. The main goal of the evaluation process is to assure the safety of the donor and to provide grafts of better quality for the recipients. The selection of candidates for ALDLT represents a complex, time-consuming, and expensive procedure. All efforts should be made to develop an effective screening protocol for the evaluation of donors, with the aim of saving substantial time and resources for a LDLT program. It should be definitively established who should cover the expenses of the evaluation of all rejected donors. We encourage all centers performing ALDLT to develop a registry to retrieve comprehensive data on the evaluation of donors. These data will constitute the scientific base to answer many questions that are still unresolved.

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