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Keywords:

  • Donor;
  • liver transplantation;
  • living donor liver transplant;
  • outcomes

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

The purpose of this study is to determine the role of liver biopsy and outcome of patients undergoing donor evaluation for adult-to-adult right hepatic lobe living donor liver transplantation (LDLT). Records of patients presenting for a comprehensive donor evaluation between 1997 and February 2005 were reviewed. Liver biopsy was performed only in patients with risk factors for abnormal histology. Two hundred and sixty patients underwent a comprehensive donor evaluation and 116 of 260 (45%) were suitable for donation, 14 of 260 (5.4%) did not complete evaluation and 130 of 260 (50%) were rejected. Four patients underwent unsuccessful hepatectomy surgery due to discovery of intraoperative abnormalities. Between 1997 and 2001, the acceptance rate of donor candidates (63%) was higher than 2002–2005 (36%), p < 0.0001. Sixty-six of the 150 eligible patients (44%) fulfilled criteria for liver biopsy and 28 of 66 (42%) had an abnormal finding. Less than half of the patients undergoing donor evaluation were suitable donors and the donor acceptance rate has declined over time. A large proportion of the patients undergoing liver biopsy have abnormal findings. Our evaluation process failed to identify 4 of 103 who had aborted donor surgeries.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

In the United States, adult-to-adult right hepatic lobe living donor liver transplantation (LDLT) developed as an effective therapy for selected patients with end-stage liver disease in the late 1990s (1). The number of cases peaked in 2001 at 512 operations or approximately 10% of liver transplantations (2). Thereafter, the volume has declined to approximately 350 cases yearly or approximately 5% of all liver transplantations. The explanation for the reduction in the number of LDLTs is multifactorial (3). Concern over donor safety is an important factor that received national attention after the highly publicized death of a donor in 2001 and the subsequent development of increased regulation and criteria for the evaluation, care and follow-up of donors and recipients. As a result of these events, some liver transplant programs may have decided not to perform LDLT. In addition, the concerns expressed by two leading transplant surgeons regarding the safety of the LDLT may have dissuaded centers from offering this procedure (4,5). Another important factor is the increased availability of deceased donors (DD) over the past several years as reflected in the increased number of deceased-donor liver transplantations (DDLT) by 25% from 4670 in 2001 to 5846 in 2004 (2). The improvement in the supply of DDs is likely due to increased efficiency of organ procurement, increased utilization of extended criteria grafts including non-heart beating donors and lower thresholds for organ acceptance. Finally, the availability of suitable living donors may limit the application of this procedure.

In the analysis presented here, we examine the outcome of patients presenting to our center for a comprehensive donor evaluation for donation of a right hepatic lobe for adult-to-adult LDLT. We report (1) the percentage of donor candidates who were rejected during the evaluation and the indication for rejection and (2) the utility and findings of the ‘reflexive’ liver biopsy, i.e. selection of patients for liver biopsy whose clinical features place them at higher risk for abnormal histology.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Our center (University of Colorado Health Sciences Center) performed our first adult-to-child LDLT in 1996 and first adult-to-adult LDLT in 1997. All adult-to-adult LDLT at our center have utilized right hepatic lobes. The recipient and donor evaluation process has changed very little since the inception of our program and has been described in detail elsewhere and summarized here (1,6). Patients listed for DD transplantation may be considered for LDLT if they are deemed ‘medically eligible’ and ‘surgically suitable’ for the procedure. To be considered ‘medically eligible’ for LDLT, the patient must have an urgency for transplantation and, in the judgment of the transplant team, must have a significant risk of dying prior to the anticipated DD transplantation. Selected patients with nonlife-threatening complications (pruritus, fatigue) may be considered for LDLT on a case-by-case basis. The model for end-stage liver disease (MELD) score is a valuable selection criterion for LDLT recipients. However, clinical judgment is as important or more important than the MELD score in recipient selection. Because the 90-day mortality associated with a MELD score ≥18 is >10%, all patients with a MELD score over 18 should be considered as potential candidates for LDLT. However, some patients with a MELD score <18 may also have a medical urgency for transplantation for LDLT. Typically, these patients experience life-threatening symptoms such as cachexia, recurrent encephalopathy or recurrent infections, which have no bearing on their MELD score. For decompensated patients with a low MELD score (<18), the chances of imminent DD transplantation are low at most transplant centers. As a result, an expedited transplantation with a live donor may be their best treatment option. Compared to viral hepatitis, patients with cholestatic liver disease (primary biliary cirrhosis and sclerosing cholangitis) are more likely to have significantly decompensated liver disease with a low MELD score. Early in our program development, we performed LDLT in critically ill patients (listed as status 2A under the old UNOS allocation system) with chronic liver disease. However, with greater experience, we rejected critically ill patients with chronic liver disease for LDLT with the following features: mechanical ventilation, hemodialysis or very low Karnofsky score.

Each liver transplant candidate who is listed for DD liver transplantation may be considered for LDLT. Patients accepted as an LDLT candidate may then accept volunteers for donation. The potential donors then undergo a preliminary screening evaluation where the following information is obtained: age, height, weight, basic medical/surgical history, relationship to potential recipient (spouses are denoted as ‘primary relatives’) and any other special circumstances. This information is reviewed by the Liver Transplantation Selection Committee and acceptable donor candidates then undergo blood tests including complete cell count, liver function tests, serum electrolytes, blood type, hepatitis C antibody, hepatitis B surface antigen and hepatitis B core antibody. If these screening tests are acceptable, the potential donor is scheduled for a comprehensive 1–2 day outpatient donor evaluation at our center, which includes complete history and physical examination (by an attending physician other than the attending for the recipient), surgical consultation, social work consultation, perioperative training session, chest radiograph, electrocardiogram, comprehensive serologic evaluation, cross-sectional imaging and a psychiatric evaluation for selected patients. The specific type of cross-sectional imaging technique utilized in the donor evaluation has varied since the inception of our program. Based on the experience and preference of the donor surgeon and radiologist, we have utilized magnetic resonance imaging, magnetic resonance cholangiography and computed tomographic imaging. This information from the comprehensive donor evaluation is presented at the weekly Liver Transplantation Selection Committee meeting. If the donor is found to be suitable, then final approval rests on liver biopsy results (in selected patients) and a detailed review of the donor anatomy on the following day by the donor surgeon and one specific radiologist who is our center's expert in cross-sectional imaging. If the donor anatomy is found suitable, then the liver biopsy (if required) is scheduled. In special circumstances where donor candidates are traveling from great distances and the likelihood for a liver biopsy is high (based on information from the screening evaluation), the donor candidate may be scheduled for a biopsy as part of their comprehensive evaluation. Since the inception of our program we have elected to perform liver biopsy ‘reflexively’, i.e. on a selective basis in donor candidates with one or more of the following clinical indications: body mass index (BMI) ≥28 kg/m2, significant history of alcohol or drug use, mild steatosis on cross-sectional imaging, mild elevations in liver function tests or positive hepatitis B core antibody IgG (see below). In almost all cases, liver biopsy was performed following review and approval of all other tests and consults during the evaluation. In addition, endoscopic retrograde cholangiography and angiography are utilized only in donors with biliary or vascular abnormalities requiring further investigation, respectively.

The following are more detailed guidelines for donor evaluation. Donor age: The absolute age ranges for donor candidates is 18–55 years. Hypertension: The presence of chronic uncontrolled hypertension or the long-term use of antihypertensive medication was a contraindication for evaluation. Heart disease: The presence or history of coronary artery disease or valvular heart disease or heart enlargement were contraindications for evaluation. Patients with isolated electrocardiographic abnormalities, e.g. primary ventricular contractions or cardiac conditions with no or minimal perioperative risk (asymptomatic mitral valve prolapse), were evaluated by a cardiology consultant. Renal insufficiency: The presence of repeatedly abnormal and unexplained serum creatinine >10% above the upper limit of normal was a contraindication for evaluation. Pulmonary disease: The presence or history of a chronic respiratory condition including asthma requiring chronic treatment was a contraindication for evaluation. Mild asthma characterized by seasonal nature, not requiring prednisone or chronic inhalation therapy, was a relative contraindication for evaluation. Smokers were asked to stop smoking prior to evaluation. A history of 20 pack-years of smoking or greater was strong relative contraindication for evaluation. BMI: Our center does not have an absolute cut off for BMI in donor candidates. Donor candidates with a BMI ≥ 30 kg/m2 are required to have a visual evaluation either in person (by presenting themselves to the transplant center) or by sending pictures to the center. Most candidates with BMI ≥ 30 kg/m2 and predominance of adipose tissue in the abdomen (high waist-to-hip ratio) are rejected for formal donor evaluation and advised to lose weight if they wish to donate. Candidates with a high waist-to-hip ratio may be accepted for formal evaluation during which a liver biopsy would be required. The evaluation of the waist-to-hip ratio is based on a subjective judgment of the donor surgeon and no formal calculation is made. Mild elevations in ALT: We do not evaluate donors with ALT >1.25-fold above the upper limit of normal. Patients with ALT between the upper limit of normal and 1.25 times the upper limit of normal (mild elevation) require a liver biopsy to be accepted for donation. Steatosis: We reject all donors whose liver biopsy shows ≥10% steatosis. Hepatic anatomy: There are not absolute anatomic contraindications for donors. However, anatomic abnormalities that may result in rejection of donors include imperforate intrahepatic vena cava (absence of intrahepatic vena cava with associated collateral vessels), hepatic cyst(s) or hepatic hemangioma (≥3 cm and in the likely transaction path). While many centers use formal equations to evaluate donor right hepatic volume, for the most part, we do not use formal assessments of liver volume in our donor evaluation. However, we reject all donors whose remnant left hepatic lobe is <300 cc. Psychosocial features: The psychosocial features that are absolute contraindications for donation include active substance abuse, overt coercion, marked immaturity or inability of the donor candidate to provide care for infant dependents during postoperative recovery.

In our analysis, the disposition of each potential donor was categorized as ‘accepted for donation’ or ‘did not complete evaluation due to change in recipient status’ (death, DDLT, too sick for LDLT due to progression of liver disease, not sick enough for LDLT due to improvement in clinical condition or other) or ‘rejected for donation’ for one of the following indications: (1) abnormal histology on liver biopsy, (2) medical problem, (3) anatomic anomaly on cross-sectional imaging, (4) psychosocial problem and (5) multifactorial causes. Some donors may have had several abnormalities or reasons for disqualification. In these cases, the actual cause of donor rejection as recorded in the minutes of our transplant selection meeting was the indication for rejection. In addition, some donors were accepted for donation, but did not undergo donor surgery because of a change in the recipient status between the time of donor approval and LDLT (death, DDLT, too sick for LDLT due to progression of liver disease, not sick enough for LDLT due to improvement in clinical condition or other). Statistical analysis was performed using Student's t-test (Microsoft Excel, Microsoft Corporation, Redmond, WA) or chi square analysis where appropriate.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Two hundred and sixty patients underwent a comprehensive donor evaluation at our center. The demographic features of these 260 patients are depicted in Table 1, and Figure 1 shows a depiction of outcomes of the donor evaluation. Most donor candidates were young, male, related to the recipient and thin. Of the 260 patients who underwent comprehensive evaluation, 116 of 260 (45%) were found suitable for donation, 14 of 260 (5.4%) did not complete evaluation due to change in recipient status during evaluation and 130 of 260 (50%) were rejected as donors. The demographics of these rejected patients are depicted in Table 1. The rejected patients had significantly higher age and BMI. The proportion of accepted candidates who were primary relatives (95 of 116) or 82% was significantly higher than the proportion of primary relatives in rejected candidates (92 of 130) or 71%, p = 0.03.

Table 1.  Demographics of 260 patients undergoing comprehensive donor evaluation
 AcceptedRejectedP
n116130 
Mean age (years)33.4 ± 9.736.9 ± 10.20.02
Age range (years)18–5419–56 
Gender M/F (%)69/47 (59/41)80/50 (62/38)Ns
Body mass index (kg/m2)25.0 ± 3.026.9 ± 3.80.0001
Body mass range (kg/m2)17.5–34.020.0–35.5 
Relationship
 Son27 (23%)18 (14%)Ns
 Friend12 (10%)24 (19%)Ns
 Daughter17 (15%)18 (14%)Ns
 Brother15 (13%)18 (14%)Ns
 Sister12 (10%)8 (6%)Ns
 Other primary relative12 (10%)6 (5%)Ns
 Other secondary relative19 (16%)32 (25%)Ns
 Other unrelated2 (2%)6 (5%)Ns
image

Figure 1. Outcomes of patients evaluated for donation.

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Of the 116 patients approved for donation, 103 of 260 patients (40.0%) were taken to the operating room for donor surgery. Thirteen patients were approved for donation, but were not taken to the operating room for donor surgery due to a change in recipient status after donor approval: DDLT prior to LDLT (7), recipient death (2), recipient worsened becoming too sick for LDLT (2) recipient improved and too well for LDLT (2). Four patients approved as donors were taken to the operating for donor hepatectomy, but were discovered to have anatomic abnormalities that were sufficiently problematic that the operation was aborted to insure the safety of the donor. These four cases are described here:

  • 1
    Thirty-six-year-old male had BMI = 30 and a normal predonation liver biopsy. During the dissection of the portal vein, it was found that the right portal vein bifurcated off the main portal vein with four or five separate branches, some of which were proximate to the main left portal vein. Because of this anatomic anomaly, we decided that the surgery should be stopped to avoid any complications and risks to the donor, with the option that this right portal vein could not be placed together on a common cuff to perform the recipient's surgery.
  • 2
    Thirty-six-year-old male with BMI = 26 and a normal pre-donation liver biopsy. Intraoperative cholangiogram indicated that a main left bile duct came off one of the branches of the right hepatic duct. In addition, the right hepatic bile duct had a very high trifurcation with two branches going to the right lobe. With this complexity of the bile duct anatomy, we elected to abort the surgery.
  • 3
    Twenty-eight-year-old female with BMI = 28 and did not have a pre-donation liver biopsy. The pre-operative MRI, performed within 1 month of surgery, was normal with no evidence of steatosis. The intraoperative findings showed gross steatosis, and intraoperative biopsy showed 80% steatosis at which time the surgery was stopped.
  • 4
    Twenty-four-year-old male with BMI = 24 and normal liver function tests and did not have a pre-donation liver biopsy. The pre-operative MRI was normal. The intraoperative findings showed a grossly abnormal liver, and intraoperative biopsy showed nonspecific hepatitis at which time the donor surgery was halted.

The specific indication in the 130 rejected donors is shown in Table 2 and Figure 1. This included 4 patients with likely nonhepatic malignancies discovered during evaluation including significant pulmonary nodule suspicious for lung malignancy, CT scan and subsequent PET scan consistent with thyroid cancer, renal mass consistent with renal cell carcinoma and serum alpha-fetoprotein level >10 000 IU/mL suggestive of gonadal tumor. The number of donors who underwent comprehensive evaluation and the percentage of donors accepted for donation, by year, are shown in Figures 2 and 3, respectively. The number of donors evaluated from the initiation of our program nearly doubled each year until 2002 when the evaluations dropped by over half compared to 2001. Thereafter, donor evaluations increased such that about 50 donors are evaluated each year. The percentage of donors approved for donation has generally decreased since the inception of our program and declined significantly after 2001. In the initial phase of our program (1997–2001), the proportion of candidates accepted for donation (63%) was more than 2-fold higher than the later phase (36%) (2002–2005), p < 0.0001. The indication for donor rejection for the two eras (1997–2001 vs. 2002–2005) is histology (10% vs. 6%), medical (6% vs. 19%*), anatomy (8% vs. 14%), psychosocial (8% vs. 16%*), multifactorial (4% vs. 7%), where *= p < 0.01.

Table 2.  Indication for rejection of 130 donor candidates
Abnormal liver histology (by biopsy)20 (16%)
 Steatosis17
 Inflammation1
 Other2
Medical problem34 (26%)
 Excess body weight7
 Cardiac6
 Elevated liver function tests or hepatitis6
 Likely nonhepatic carcinoma4
 Other11
Abnormal hepatic anatomy29 (22%)
 Hepatic cysts5
 Hemangioma3
 Small left hepatic lobe10
 Venous anomaly5
 Other6
Psychosocial problem32 (25%)
 Declined donation17
 Active substance abuse4
 Other11
Multifactorial problem15 (12%)
image

Figure 2. Number of donor evaluations by year.

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image

Figure 3. Percentage of donors approved following evaluation.

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Of the 260 donor candidates, 110 were not considered for liver biopsy due to early rejection for the following problems: medical (30), hepatic anatomy (27), psychosocial (28), multifactorial (12), incomplete evaluation due to change in recipient status (13). Of the remaining, 150 donor candidates, 66 (44%) fulfilled criteria for liver biopsy and had the procedure. We evaluated the biopsy simply in terms of whether the biopsy was normal (38 of 66 or 58%) or abnormal (28 of 66 or 42%), including 19 steatosis, 2 inflammation, 2 increased iron deposition and 5 other (excess copper deposition (1), cholestasis (1), pericentral sclerosis (1), focal regenerative changes (1), sinusoidal vascular congestion (1)) see Figure 4A). Because the result of the liver biopsy was not the sole determinant of donor disposition, we also evaluated the impact of the liver biopsy of the outcome of the donor candidate, as depicted in Figure 4B. Of the 38 patients with a normal biopsy, 7 were rejected for the other following indications: splenomegaly (1), hepatic cystic disease (1), psychosocial concerns (2), elevated liver function tests (1), bile duct anomaly (1) and donor pregnancy (1). Of the 28 patients with an abnormal biopsy, 2 patients were accepted for donation (due to the minimal inflammatory changes) and 26 were rejected for donation. Of the 26 rejected for donation with an abnormal biopsy, the biopsy was the sole indication for rejection in 20, a contributing cause of rejection in 4 patients and unrelated to the reason for rejection in 2 patients.

image

Figure 4. (A) and (B) Outcomes relative to liver biopsy.

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Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

There are several important findings regarding the outcomes of the donor evaluation process. We found that less than half of the patients undergoing evaluation were ultimately found acceptable for donation. In addition, the percentage of patients who were rejected has increased over time; we currently reject approximately two-fold as many donor candidates compared to the early years of our program (7). The explanation for the increased rejection rate is not clear, but is likely due to one or more of the following. With the highly publicized donor death in 2001 and increased scrutiny regarding donor safety, we may have increased our threshold for donor acceptance and rejected a greater proportion of donors. In accordance with this view is the significant decrease in the donor acceptance rate after 2001. Another factor could be related to a ‘front-loaded’ effect. At the inception of our LDLT program we had several hundred patients listed for DDLT some of whom were excellent candidates for LDLT. Perhaps in our early experience, a proportionally higher number of these recipients with ideal donors were identified and accepted for LDLT at a high rate. Once the ideal donor-recipient pairs were transplanted, the remaining patients were considered for LDLT and their donors were rejected at a higher rate during the evaluation process. Institution of the MELD score as the basis for allocation of DD organs may have also reduced the number of LDLTs. The MELD has reduced the number of patients who have died on the transplant list and has facilitated expeditious transplants in sicker patients. Therefore, the number of LDLTs, which are often used to transplant patients with a medical urgency for transplant, may have been reduced because of the salutary effects of the MELD. Finally, with greater experience, we may have elected to evaluate donor candidates that would not have been considered earlier, e.g. a desperate recipient whose sole potential donor candidate has marginal social circumstances, excess body weight and advanced age. These marginal donor candidates may have been subsequently rejected at a higher rate during the evaluation process. The increased rejection rate based on medical and psychosocial indications between 2002 and 2005 supports this concept.

The donor evaluation process is quite complex, and the indications for rejecting specific donors are not always straightforward. As a result, the description of this process may be equally complicated. For example, we found that the approval of a donor did not always lead to donor hepatectomy. Over 10% of approved donors did not undergo donor surgery due to a change in the recipient status, usually a DDLT that occurred between donor approval and the scheduled date of LDLT. In addition, the indication(s) for donor rejection were often complex. Thirteen donor candidates did not complete their evaluation due to a change in the recipient status, i.e. DDLT, death, clinical improvement or clinical deterioration precluding LDLT. The evaluation process for some donors did not necessarily occur over 1 to 2 days. In some cases, the final decision on the donor may have taken several days to weeks. The reasons for the prolonged evaluation in these donor candidates may have been due to ambivalence of the donor's spouse (or significant other), which may have required weeks to obtain a final disposition, donor's unwillingness to consent to surgery due to life events that may require weeks or months to resolve (military deployment, upcoming marriage, etc.). In addition, some of the donors had ongoing testing to follow-up on an abnormality found during donation and before completion of testing the recipient underwent DDLT. In 12% of cases the reason for donor rejection was multifactorial. For example, a donor candidate could be rejected for the presence of a minor electrocardiographic abnormality, advanced age, above normal BMI and complex hepatic anatomy. In addition, some patients may have had one or more abnormalities identified during the evaluation, but were rejected for a completely different indication. In fact, 18% (7 of 38) of patients with normal biopsies were rejected for donation based on another reason and nearly 25% of candidates with abnormal liver biopsies were rejected, in part, for other indications. For example, a patient may have had significant steatosis on biopsy, but declined to donate prior to learning of the abnormal histologic findings. There were a few patients who lived long distances from out center and had a marginal BMI for donor evaluation (BMI > 30). When these donors presented for the formal evaluation, they were judged to be too obese for donation. It may have been possible to exclude these candidates simply on the basis of the BMI. However, we have found that BMI itself is not necessarily the best means of rejecting donor candidates with excess body weight. We have found that the distribution of body fat is also an important determinant that requires a visual inspection to determine. Patients with high BMI and fat distribution in hips and thighs (low waist-to-hip ratio) were more likely to be accepted as donors than patients with abdominal fat (high waist-to-hip ratio). Some of these marginal donors were evaluated and rejected based on obesity after the formal evaluation. These donors were advised to lose weight to be deemed suitable donors. There were also a few patients who had normal liver function during the preliminary screening process whose liver function tests were abnormal during the formal evaluation. This explains why some of the donor candidates were rejected for these findings during the formal evaluation. We have no explanation for the change in LFTs between these two points of evaluation. In comparing data from our center to other programs, one must recognize that the donor evaluation process at each transplant center may significantly impact the outcomes of the donor evaluation. Prior to the comprehensive donor evaluation, some centers require a formal meeting during which the risks of the procedure are frankly discussed. This approach may eliminate less-committed donor candidates prior to the formal evaluation process and therefore fewer donor candidates may be rejected during the comprehensive donor evaluation process. Unique requirements at specific centers may also influence the outcomes of the donor evaluation. While our center does not have a specific requirement for graft weight-to-recipient weight (GWRW) cutoff, the donor's weight must, in general, be not less than 70% of the body weight of the recipient. However, other centers follow a strict GWRW cutoff in the selection of donor candidates. Finally, the specific sequence of the evaluation tests is an important consideration. We obtain blood chemistries, liver function tests and hepatitis serologies prior to the comprehensive evaluation process. Therefore, we may be less likely to reject candidates for abnormal serologies during the formal evaluation compared to centers that do not follow this practice. Unfortunately, we do not have comprehensive records reflecting the number of donor candidates who were rejected during the preliminary screening phase of the evaluation and the indication for rejection.

We noted differences in the candidates who were accepted vs. those rejected for donation. The accepted candidates were, in general, younger, less obese and more likely to be a primary relative compared to the rejected candidates. The higher proportion of younger, thinner patients who were accepted for donation might be expected, because these patients were likely better operative candidates. The lower degree of relatedness in the rejected donors may reflect the bias of out center toward accepting less-related candidates as donors. Alternatively, the less-related candidates may not have been as committed to become donors and may have therefore been rejected at a higher rate.

We were troubled that 4 patients were taken to the operating room without successful completion of the donor surgery due to abnormalities discovered intraoperatively. One of these patients had biliary anomalies and another had significant venous anomalies. Perhaps improved cross-sectional imaging techniques could have discovered these problems prior to the donor surgery. The 2 other patients with histologic abnormalities might have been discovered if we had instituted a policy of mandatory liver biopsy for all donors as part of the comprehensive donor evaluation. At some centers, all potential donors undergo liver biopsy to discover any histologic abnormalities prior to surgery. The advantage to a mandatory liver biopsy for all donor candidates is the discovery of histologic abnormalities prior to the donor surgery, thereby preventing aborted donor surgeries. The disadvantages include complications related to the biopsy, which are typically estimated at 1%. In addition, the mandatory biopsy in most patients would simply demonstrate normal histology. Another disadvantage is that histologic abnormalities could develop between the time of a normal biopsy and donor surgery. For patients who have significant steatosis (the most common identified abnormality) identified on the mandatory biopsy, a subsequent biopsy would be required prior to donation. There are reports of patients undergoing two liver biopsies with steatosis identified on the first biopsy and a subsequent liver biopsy (8). Such patients were still rejected as suitable donors despite having had two procedures with no medical indication. At our center, we have elected to perform liver biopsy only for specific clinical indications or ‘reflexively’. The advantages to this approach include avoidance of liver biopsy in patients who are at low risk for histologic abnormalities (only 25% patients underwent liver biopsy at our center) and the avoidance of biopsy complications. The obvious disadvantage is that a small fraction of patients may undergo surgery without successful completion of the donor hepatectomy due to undiscovered histologic abnormalities. The appropriate use of liver biopsy in the donor evaluation (mandatory vs. reflexive) is not clear. Because the negative outcomes in each group are so small, we believe that there is insufficient data to determine which approach (mandatory vs. reflexive) is best. Therefore, assessment of the role of liver biopsy in the evaluation of the living donor must be critically examined on an ongoing basis including the experience from different LDLT centers.

Other centers have reported their findings relative to the role of the liver biopsy in the donor evaluation. A recent study showed that hepatic steatosis (>10% steatosis) was present in 78% of patients with BMI >28 kg/m2 (9). As a result, most centers will biopsy almost all donors with BMI >28 kg/m2. However, one report demonstrated a poor correlation with BMI and hepatic steatosis. Ryan et al. found that 73% of overweight (BMI > 25) donors had little or no hepatic fat and 9% of candidates with a BMI ≤ 25 had 10% or greater steatosis (10). Most centers will exclude donors who have >10% steatosis on liver biopsy; in part, because in DD transplantation, hepatic steatosis is associated with poor post-transplant graft function, but more importantly because hepatic steatosis increases the risk of bleeding and complications in the donor. However, there is no definitive data indicating the safe upper limit of steatosis in a living donor graft. In fact, there is a recent report from Korea regarding outcomes following LDLT using steatotic grafts with up to 30% steatosis (11). These investigators showed that steatosis resolves within 10 days of surgery and that there was no measurable increase in donor morbidity or graft dysfunction in the small group of patients studied.

There are several early reports regarding the outcomes of donor evaluations. Renz et al. reported outcomes of 75 donor candidates for 38 potential pediatric LDLT recipients (12). Of the 75 candidates, 17 declined donation, 13 had obvious exclusion criteria and 45 underwent evaluation of which 35 (78%) were excluded for the following reasons: medical history (8), blood type incompatible (8), psychosocial (7), donor size (5), hepatitis (4) and other (3). Therefore, only 10 of the candidates were found suitable. Sterneck et al. considered 69 pediatric recipients who were deemed suitable for LDLT (13). There were 73 donor candidates for these 69 patients and only 24 were rejected for donation for the following indications: psychosocial (6), cardiovascular risk factors (5), fatty liver (4), blood type (2) and the remaining 45 patients (65%) were accepted for donation. The authors commented in their article that the high rate of acceptance may have been related to a referral bias in that many patients came to their center specifically for LDLT. In two studies from Japan, the acceptance rates of donors were even higher, likely reflecting a referral bias in that LDLT is the only means of transplantation in that country (14,15). Finally, Baker et al. reported outcomes in 54 donor candidates, 18 of whom were rejected in the preliminary phase (due to incompatible blood type, donor size and medical history) (16). Of the remaining 36 candidates who underwent formal evaluation, 23 (64%) were acceptable. In a previous publication from our center, 26 donors underwent formal evaluation and 15 (58%) were ultimately able to undergo donor surgery (7). These early reports are characterized by (1) relatively small number of donor evaluations, (2) relatively high donor acceptance rates, which may reflect selection of ideal donor-recipient pair, or a ‘front-loaded’ effect described above.

A recent study that included a much more detailed description of the donor evaluation process and many more patients than there earlier studies found similar results compared to our findings (8). This center adopted the practice of mandatory liver biopsy on all donor candidates after a donor death ascribed to congenital lipodystrophy, which was not discovered in the preoperative evaluation. Eighty-six percent of donor candidates were rejected following the evaluation. Liver biopsies were performed in 116 of the donor candidates and complications were observed in 2 patients (1.6%).

We have learned from every case that we have performed and continue to learn by the shared experience of other centers. The current shortcomings of our approach would be that we could have likely detected histologic abnormalities in 2 of the aborted donor surgeries if we had performed protocol liver biopsies on every donor candidate. However, we would have performed many more liver biopsies and may have seen complications after some of these procedures. As described above, the basic problem regarding the application of liver biopsy in the donor candidate evaluation is that the current noninvasive screening modalities (liver function tests and cross-sectional imaging) and the clinical predictive markers (age, BMI, alcohol intake history) are not very sensitive. As a result, centers may either biopsy all patients (resulting in relatively few abnormal findings and potentially a significant number of procedural complications) or biopsy selected patients (resulting in a higher proportion of abnormal findings, but potentially a higher number of ‘aborted’ donors with abnormal hepatic histology discovered in the operating room). The problem could potentially be resolved or partially resolved with the development of more sensitive screening tests, which could allow for a more focused application of liver biopsy. Perhaps the newer generation radiologic imaging modalities, such as multidetector computed tomography, as well as future improvements in software capabilities for cross-sectional imaging will increase the sensitivity for detecting abnormal hepatic histology. The other two aborted cases involved abnormal vascular or biliary anatomy discovered in the operating room. We are unsure whether these problems could have been detected with more invasive preoperative testing, e.g. visceral angiography or ERCP. However, given the higher rate of complications with these procedures we do not believe that angiography and ERCP should be performed in every candidate. In our experience, we have used ERCP in fewer than 5 donor candidates and visceral angiography in fewer than 5 donor candidates. As noted in the Methods section, the final step in the donor evaluation process (once the donor candidate has been approved for donation) is a comprehensive and detailed review of the donor candidate's vascular and biliary anatomy by the donor surgeon and our single best cross-sectional abdominal radiologist. There are numerous vascular and biliary anomalies that can lead to disqualification of a donor candidate. Three of the most important are (1) donor bile ducts or veins, which cross between the right and left lobes and could be transected during surgery, (2) multiple minor anomalies (including recipient anomalies), each of which would not preclude successful donation, but together prohibitively increase the risk of complications (for example, trifurcated donor portal vein, diminutive donor hepatic vein requiring vascular reconstruction and thrombosed recipient portal vein requiring vascular graft) and (3) any vascular or biliary donor anomalies that could compromise the integrity of the remnant donor left lobe.

In summary, we report the outcomes in patients undergoing evaluation for living donor evaluation. We found that the majority of patients evaluated as donors were rejected and that the percentage of patients rejected for donation has increased over the years. In addition, we believe that donor evaluation with ‘reflexive’ liver biopsy is an appropriate approach but requires continued critical evaluation.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References