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Keywords:

  • Liver grafts;
  • liver transplantation;
  • living-related liver donors

Abstract

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

The shortage of deceased organ donors has created a need for right lobe living donor liver transplantation (RLDLT) in adults. Concerns regarding donor safety, however, necessitate continuous assessment of donor acceptance criteria and documentation of donor morbidity. We report the outcomes of our first 101 donors who underwent right lobectomy between April 2000 and November 2004. The cohort comprised 58 men and 43 women with a median age of 37.8 years (range: 18.6–55 years); median follow-up is 24 months. The middle hepatic vein (MHV) was taken with the graft in 55 donors. All complications were recorded prospectively and stratified by grade according to Clavien's classification. Overall morbidity rate was 37%; all complications were either grade 1 or 2, and the majority occurred during the first 30 days after surgery. Removal of the MHV did not affect morbidity rate. There were significantly fewer complications in the later half of our experience. All donors are well and have returned to full activities. With careful donor selection and specialized patient care, low morbidity rates can be achieved after right hepatectomy for living donor liver transplantation.


Introduction

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

Living donor liver transplantation (LDLT) has become an accepted therapy for patients with end-stage liver failure in many transplant centers worldwide, and further growth is expected as the gap between the need and availability of deceased donor liver transplants increases (1–3). An ongoing concern about LDLT, however, is donor risk. This issue has prompted the liver transplant community to establish criteria for centers planning to initiate a LDLT program (4,5), and to promote complete documentation of donor morbidity and mortality in centers with active LDLT programs.

Right lobe LDLT was initiated at our center in 2000, and now accounts for 30% of our total adult liver transplantation activity. Herein, we report our 5-year experience and clinical outcomes of our first 101 donors.

Patients and Methods

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

Between April 2000 and November 2004, 469 patients were evaluated for liver donation at Toronto General Hospital; during this time period 101 of these patients underwent right hepatectomy (Figure 1). All living donors were deemed suitable for surgery after completing an evaluation process that included an initial health-screening survey, blood tests, viral serology, imaging studies, and medical and psychiatric assessments by health-care professionals independent of the transplantation team. Liver biopsies were performed selectively in patients in whom liver steatosis was suspected, and in those with serum liver enzyme abnormalities. Donors with a body mass index >35 were not evaluated until they completed a successful weight loss program. Absolute exclusion criteria were any underlying medical condition that was considered to increase the risk for complications, ABO incompatibility, positive hepatitis serology, underlying liver disease, inadequate graft size, steatosis >10% and abnormal biliary anatomy (e.g. branches to left lobe arising from right duct).

image

Figure 1. Live donor liver transplantation program at the University of Toronto from March 2000 to November 2004.

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A multi-step consent process involving two different surgeons on separate occasions was used, during which the operative procedure and potential complications were described in detail. Donors were informed that the risk of morbidity and mortality was 40% and 0.5%, respectively.

Triphasic computerized tomography (CT) was performed to assess arterial and venous anatomy, to assess removal of the middle hepatic vein (MHV), and to estimate the volume of the whole liver, right lobe and remaining liver using OSIRIS imaging software (Digital Imaging Unit, University Hospital of Geneva, Geneva, Switzerland). The liver resection plane was assessed to ensure that the residual liver weight/total liver weight ratio would be equal to or greater than 30%. The estimated graft-to-recipient weight ratio (GRWR) was calculated by dividing the right lobe volume by the recipient's weight; a ratio of at least 0.8% was considered acceptable. Magnetic resonance cholangiography (MRCP) has been used to assess biliary anatomy since July 2001 (6).

Patients donated 1–2 units of autologous blood within 1 month of the planned surgery date. Prophylactic antimicrobial (cefazolin, metronidazole) and anti-deep vein thrombosis (DVT; Heparin 5000 U s.c.) therapy was initiated immediately prior to surgery. Pneumatic compression stockings have been used routinely over the past year to reduce the risk of DVT. Epidural analgesic delivery was offered to all donors.

A detailed technical description of the donor operation has been described previously (1). Briefly, surgery was performed through a right subcostal 'hockey-stick' incision (7). An intraoperative cholangiogram was performed with fluoroscopy to verify biliary anatomy and to determine whether there were biliary anomalies that would preclude resection. Prior to the routine use of MRCP, surgery was aborted in two donors because of abnormal biliary anatomy detected by cholangiography; these patients were not included in the analysis. The right hepatic artery and right portal vein(s) were dissected and defined. The right lobe was mobilized off the inferior vena cava (IVC); accessory right hepatic veins exceeding 8 mm in diameter were preserved for revascularization in the recipient, and the right hepatic vein was encircled. The Hydro-Jet Dissector (ERBE, Teubingen, Germany) and the Cavitron Ultrasonic Aspirator (CUSA Excel, Valleylab, Boulder, CO) were used to transect the liver parenchyma along the plane of the MHV; the Hydro-Jet was used exclusively in the last 80 donors. When the MHV was removed with the graft, it was divided 1–2 cm above its termination with the IVC in order to preserve segment IVa veins and to reduce risk of injury to left hepatic vein. Parenchymal oozing was controlled with electrocautery without inflow occlusion. A red blood cell scavenging device was used routinely. The right bile duct(s) and the hilar plate were divided sharply after 80% of the parenchymal dissection had been completed. Heparin (5000 U) was given i.v. 5 min before removal of the graft. The right hepatic artery, right portal vein and the hepatic veins were clamped and divided, and the graft was removed and flushed with cold University of Wisconsin solution (Viaspan; Dupont, Wilmington, DE). A cholangiogram was performed at the conclusion of the procedure.

Donors were managed in an intensive care step-down unit for the first 48 h, and then on a regular surgical ward. Antibiotics were continued for 24 h postoperatively. Complete blood counts, coagulation profile and serum liver tests were monitored daily. Patients were given parental magnesium and phosphate infusions routinely until tolerating diet, and then were transitioned and discharged home on oral magnesium and phosphate as required (8–10). Deep venous thrombosis (DVT) prophylaxis continued with heparin (5000 U s.c.) and sequential compression stockings while in hospital and with low molecular weight heparin (dalteparin sodium injection; Pharmacia, Mississauga, Ontario) 5000 IU s.c. daily for 6 weeks after discharge. All patients underwent routine Doppler ultrasound of the abdomen on the third postoperative day to assess vessel integrity and flow. Donors were seen in follow-up with routine laboratory investigations and abdominal ultrasound at 1 month, 3 months, 6 months and then annually after surgery. All complications were recorded prospectively and stratified according to the classification scheme devised by Clavien et al. (11).

Continuous variables are presented as mean ± standard deviation, or medians with ranges, and analyzed by two-tailed Student's t-test. Categorical variables are presented as proportions and analyzed by Chi-square test. A p-value <0.05 was considered statistically significant.

Results

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

Donor characteristics

The mean age was 37.7 ± 11.7 years; 57% were male, and most were either a child or sibling of the recipient (Table 1). The volume of liver removed was 990 ± 227 mL, which left the donor with a residual volume of 601 ± 146 mL or 37.9 ± 6.2 % of their initial liver volume (Table 2). The GRWR was 1.4 ± 0.4%; inclusion of the MHV with the graft neither affected graft nor residual liver volume. The mean number of veins requiring revascularization in the recipient was 2.0 ± 0.8 (range: 1–4); and the mean number of bile ducts for anastomosis was 1.3 ± 0.5 (range: 1–4).

Table 1. Demographic data of RLDLT
CharacteristicNumber (n)
  1. Values are mean ± standard deviation.

  2. BMI: Body mass index [weight (kg)/height (m)2].

Number101
Age (years)37.7 ± 11.7
Sex
 Male58 (57%)
 Female43 (43%)
Relationship
 Child42 (41%)
 Sibling24 (24%)
 Parent10 (10%)
 Spouse5 (5%)
 Other biologic3 (3%)
 Friend17 (17%)
Body weight (kg)73.0 ± 12.6
BMI25.9 ± 3.99
Table 2. Operative characteristics of RLDLT
CharacteristicNumber (%)
  1. Values are mean ± standard deviation.

  2. RLD + MHV: Right lobe donor with middle hepatic vein; RLD − MHV: Right lobe donor without middle hepatic vein; GRWR: Graft recipient weight ratio.

Procedure
 RLD + MHV55 (54.5%)
 RLD − MHV46 (45.5%)
Total liver volume (mL)1596 ± 396
Volume of liver removed (mL)990 ± 227
Volume of liver retained (mL)601 ± 146
% of total liver volume retained37.9 ± 6.2
GRWR (%)1.4 ± 0.4
Graft anatomy
 No. of arteries1.0 ± 0.14
 No. of hepatic veins2.0 ± 0.84
 No. of bile ducts1.3 ± 0.51
Procedure time (min)397 ± 89
 Median (min)390
Estimated blood loss (mL)960 ± 546
 Median (mL)800
Blood transfusion
 Allogenic3 (3)
 Autologous14 (14%)
 Cell-saver63 (63%)

The median operative time was 390 min (range: 234–672 min). There were no intraoperative complications. Estimated blood loss was 800 mL. Fourteen patients (14%) received autologous transfusion either intra- or postoperatively, and 63% received blood from the cell saver (mean volume 453 mL) during surgery. Three patients required transfusion with allogeneic blood during hospital stay; in two because of postoperative bleeding, and in the other because the autologous blood was mislabeled.

Postoperative liver tests are shown in Figure 2. Most values peaked on postoperative day 1, although serum bilirubin values didn't peak until day 7 in some patients. The mean number of days for the International normalized ratio (INR) (<1.2) and bilirubin (<20μmol/L) values to normalize was 8.5 ± 15.5 and 13.4 ± 15.8, respectively. There was no difference in the peak values or the time for complete normalization between donors who had the MHV taken or preserved. All donors currently have normal liver tests. The mean length of hospitalization was 7.4 ± 2.1 days.

image

Figure 2. Peak elevation of liver function tests. POD# represents the day of peak elevation.

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Donor complications

The overall complication rate was 37% (Table 3). All complications were classified as either grade I or II (11,12). No patient suffered life-threatening organ dysfunction or residual disability. The complication rate during the first 30 days postoperatively was significantly lower in the later half of our experience (Table 4). All donors are currently alive and well, and have returned to their normal daily activities.

Table 3. Total complications of RLDLT classified by severity
ComplicationNumber (n)Operative intervention (n)
  1. Severity based on Clavien classification (10). Endoscopic implies ERCP or radiologically directed drainage catheter.

GRADE I
 Urinary tract infection/recatheterization4 (4%) 
 Arrythmia1 (1%) 
 Depression2 (2%) 
GRADE II
 Incisional hernia or repair9 (9%)9 (Operative)
 Wound infection5 (5%) 
 Bleeding (reoperation)4 (4%)4 (Operative)
 Subphrenic/pleural collection4 (4%)4 (Percutaneous)
 Bile leak3 (3%)3 (Endoscopic)
 Pulmonary emboli2 (2%) 
 Pneumonia2 (2%) 
 Partial bowel obstruction1 (1%) 
GRADE III
None
GRADE IV
None
Total37 (37%)21 (21%)
Table 4. Learning curve: complications during the first 30 days in the 1st 50 and 2nd 51 donors
Complication1st 50 cases2nd 51 cases
  1. Early complications are less than 30 days after surgery.

  2. *p < 0.05.

Bleeding22
Bile leak30
Subphrenic/pleural collections21
Pulmonary emboli10
Wound infections30
Arrythmia10
Urinary tract infection/recatherization40
Fascial dehiscence12
Total*175

Complications during first 30 days

The most common serious early complication was postoperative bleeding, which occurred in four patients on postoperative day 1; all were taken to the operating room and the source of bleeding in all four was a small artery in the hilar plate. Other early complications included bile leak (3%), subphrenic or pleural collections requiring drainage (3%) and pulmonary embolus (1%). Two of the three bile leaks were treated with ERCP, stent placement and papillotomy; the other was treated with a percutaneous drain. Temporary percutaneous drainage of a subphrenic or pleural effusion was required in three patients. Three patients required reclosure of a partial fascial dehiscence located at the junction of the midline and subcostal portion of the incision.

Complications beyond 30 days

Twelve (12%) donors were readmitted to hospital for treatment of various complications. Incisional hernia was the most common late complication (n = 6), and was treated surgically. Late wound infections requiring open drainage developed in two patients. The most serious late complication was pulmonary embolism, which was diagnosed 1-month postoperatively in one donor. Pneumonia developed in two donors 2 months after surgery, and was treated with a course of i.v. antimicrobial therapy in hospital. One patient was readmitted for a partial small-bowel obstruction that resolved with bowel rest and hydration. Depression requiring medication or psychiatric counseling developed in two donors after the recipient died.

Discussion

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

RLDLT rests on the assumption that the donor operation can be performed safely. Our study shows that with careful donor selection and specialized care, low morbidity rates can be achieved. Further, we show that the rate of early postoperative donor complications is reduced with experience.

Informed consent requires full disclosure of potential risks of complications. To date, it has been difficult to quantitate precisely the risk of morbidity, as many studies under report minor complications (13,14). A crude complication rate of 31% (54 events in 174 donors) has been reported in a review of 12 studies of right lobectomy in live donors by Beavers et al. (15). In our study, we have recorded all complications in a prospectively maintained database, and have followed the donors closely in our clinics during the first year and annually thereafter. We, therefore, believe that our findings accurately represent the actual risk to the donor.

Careful donor selection is clearly essential to ensure good outcomes. The value of a multidisciplinary evaluation process cannot be overemphasized. To minimize potential conflicts of interest in our program, donors are investigated by a nurse practitioner, administrative assistant and general internists who do not look after transplant patients. More than half of the prospective donors are eliminated for consideration based on the health screening survey, incompatible blood group and body mass index. The remaining patients are disqualified mostly because of anatomical concerns detected by imaging investigations.

Triphasic CT scanning is used predominately to assess arterial and venous anatomy, and to guide operative planning. The MHV and its tributaries from liver segments 4a, 4 b, 5 and 8 are scrutinized carefully to determine whether the MHV should be taken with the graft or preserved in the donor. Several variables are taken into consideration when determining the plane of resection: size of MHV; size of venous tributaries to segments 4, 5 and 8; presence of venous collaterals between segments 5 and 8 to the right hepatic vein or between segments 4 and left hepatic vein; the volume of segment 4; residual donor liver volume; clinical status of the recipient and GRWR. We have generally advocated removal of the MHV to optimize venous drainage of segments 5 and 8, which reduces the risk of graft congestion (1,16). However, there are situations where we believe that the MHV should be preserved: small donor residual volume (i.e. <30% of original volume); narrow segment 4; venous drainage of segment 4b is predominately via the MHV; venous drainage of segments 5 and 8 is predominately via the right hepatic vein. We prefer to retain the MHV with the graft when the recipient is critically ill (e.g. MELD >30), in the presence of portal hypertension and when the GWRW ratio is less than 0.9% (14,16,17). The donor, however, is our first consideration and if inclusion of MHV is not possible, we encourage families to explore whether other donor might be available.

Pulmonary embolism is a well-recognized cause of donor death (17,18). Recommendations to reduce the risk of this complication include cessation of smoking, discontinuation of oral contraceptives for 6 weeks and avoidance of donors with BMI >30 (17). Some groups have also advocated extensive hematological work-ups to exclude donors with hypercoagulable disorders (19). The value of this approach is controversial, however, because minor abnormalities with no clinical relevance are often detected. After discussion with a team of hematologists we initially elected to treat donors with a combination of anticoagulation and compression stockings. In our early experience, however, nonlife-threatening pulmonary embolism developed in two donors after a 5–6 h car trip home 1 month after donation. We have since extended anticoagulation with deltaparin for a total of 6 weeks, recognizing the absence of evidence supporting this approach, and have advised against any long distance travel during this time period.

Reoperation for bleeding was necessary in four patients (4%) in our series. Bleeding occurred during the first 24 h, and was recognized before any hemodynamic changes apart from mild tachycardia developed. In all patients, the bleeding site was located at the hilar plate. Heparin may have been a contributing factor in the development of bleeding in two donors because the partial thromboplastin time was elevated in both donors during the first 24 h. To reduce the risk of bleeding we have modified our surgical technique in cutting across the hilar plate and administer protamine to reverse the effect of heparin.

Bile leak from the cut surface of the liver occurs in approximately 5–10% of right lobe donors (20–27). A bile leak developed in three donors during our initial experience, but none in the last 80 donors. In contrast with several reports, biliary strictures have not developed in any of our donors. It is difficult to account for this low rate of biliary complications but several factors may be involved. First, the Hydro-Jet dissector, which we have used in the last 80 donors, facilitates meticulous dissection and identification of smaller bile ducts that can be either ligated or clipped before division. Second, we often repeat an intraoperative cholangiogram immediately before the bile duct is divided to ensure the proposed level and angle of division is accurate. This practice not only minimizes the risk of injury to the left duct system, but also increases the likelihood of achieving a single duct for the recipient team, which we have found significantly lowers the risk of bile duct complications in the recipient (manuscript in preparation). Third, we always repeat an intraoperative cholangiogram at the conclusion of the procedure. In several donors, we have revised the closure of the right bile duct stump(s) because of dye extravasation or identification of an apparent narrowing of the left bile duct.

The reported rate of complications related to abdominal surgery, including wound infection, small-bowel obstruction and incisional hernia, in living donors is 9–19% (12,19–22,27). In our series, wound complications that ranged from superficial infections to incisional hernias were common. Incisional hernias often do not manifest for several months, and all have required surgical repair. No complications have become apparent after 1 year, an experience that was consistent with other reports of LDLT documenting an excellent quality of life beyond the first year with little long-term morbidity (28–31).

The morbidity rate has decreased significantly since the inception of our LDLT program. We experienced a learning curve with LDLT despite a preexisting case volume of approximately 180 major hepatobiliary oncology resections and 120 liver transplants per year. Surgical groups in Hamburg and Chicago have also shown a reduction in complications with LDLT (17,32,33). Programs with large patient volumes of hepatectomy generally have better short-term surgical and long-term survival outcomes (34,35). Between 1997 and 2000, more than 80% of the total experience of LDLT in the United States was accounted for by 14 centers. Whether the same safety outcomes can be achieved by centers performing fewer liver resections merits further study. Our study suggests that volume alone is not the sole determinant of outcome; other factors such as our center's focus on continuous quality improvement processes may be equally or more important (36).

LDLT is an effective lifesaving procedure for patients with end-stage liver disease. The demand for right lobe LDLT in North America will continue to increase because of the critical shortage of donor organs. Although we have shown that right hepatectomy can be performed with low morbidity, it remains a daunting operation with unique surgical and ethical challenges. Comprehensive documentation of complications and long-term follow-up will continue to be required to define donor risk and to advance the field.

References

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