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Keywords:

  • Complications;
  • graft survival;
  • live donor;
  • liver transplantation;
  • outcome;
  • patient survival

Abstract

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

We present our program experience with 85 live donor adult liver transplantation (LDALT) procedures using right lobe grafts with five simultaneous live donor kidney transplants using different donors performed over a 6-year period. After an ‘early’ 2-year experience of 25 LDALT procedures, program improvements in donor and recipient selection, preoperative imaging, donor and recipient surgical technique and immunosuppressive management significantly reduced operative mortality (16% vs. 3.3%, p = 0.038) and improved patient and graft 1-year survival in recipients during our ‘later’ experience with the next 60 cases (January 2001 and March 2005; patient survival: early 70.8% vs. later 92.7%, p = 0.028; graft survival: Early 64% vs. later 91.1%, p = 0.019, respectively). Overall patient and graft survival were 82% and 80%. There was a trend for less postoperative complications (major and minor) with program experience (early 88% vs. later 66.7%; p = 0.054) but overall morbidity remained at 73.8%. Biliary complications (cholangitis, disruption, leak or stricture) were not influenced by program experience (early 32% vs. later 38%). Liver volume adjusted to 100% of standard liver volume (SLV) within 1 month post-transplant. Despite a high rate of morbidity after LDALT, excellent patient and graft survival can be achieved with program experience.


Introduction

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

Live donor liver transplantation is a surgical innovation that has been developed to address the issue of organ shortages. In pediatric patients, live donor liver transplantation has helped to reduce waiting list mortality (1) and has served as a stimulus to begin live donor programs for adult patients (2). Opponents of live donor liver transplantation cite evidence of increased morbidity and worse patient and graft survival compared to deceased donor transplantation (3–5). Since the potential for donor complications in the right lobe donor is significant (6), ethical debate has arisen regarding the appropriateness of live liver donation in the setting of potentially worse recipient outcome (7).

In this article, we provide our experience in performing 85 live donor adult liver transplant procedures utilizing right lobe grafts between December 1998 and March 2005. The impact of program maturation and experience, improved patient selection and preoperative imaging, modifying surgical technique and immunosuppression has on recipient survival and outcome is explored.

Methods

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

Patient selection

All recipients of right lobe live donor grafts went through complete transplant evaluation and were listed with the United Network for Organ Sharing (UNOS). Living donors were genetically or ‘emotionally’ related to the recipients and also underwent complete evaluation as described previously (8). Donors were volunteers and were not solicited by the transplant team. Since recipient morbidity and mortality were anticipated to be significant, recipients were not offered live donation unless the risk of death from their liver disease was greater than the risk of the procedure. Clinical determination of need was based on a variety of factors including the recipient's model for end-stage liver disease (MELD) score, comorbid conditions, quality of life, and likelihood of life threatening events (variceal bleeding etc.). Asymptomatic patients with low MELD scores with a very low likelihood of morbidity or mortality from their liver disease were discouraged from live donation and observed expectantly on the UNOS waiting list (9). All recipients were reevaluated by a hepatologist prior to transplantation to ensure suitability for live donor adult liver transplantation (LDALT).

Donors were evaluated by an independent medical team who were not involved with the care of the recipient. Suitable donors were between ages 18–55, had compatible blood type, were free of underlying disease, had an estimated right lobe graft size of at least 0.8% of the recipient's body weight, and were freely volunteering to donate. Donors with a body mass index >28 underwent routine liver biopsy if they were otherwise acceptable. Donor outcomes were recorded prospectively in a comprehensive database. No donor deaths occurred. Donor morbidity was approximately 35%. Three donors required reoperation; one for bleeding, one for suspected infected hematoma and one for portal vein (PV) thrombosis that was repaired. All are doing well currently.

Results for donor morbidity and quality of life have been published previously by our group (8,10–12).

Operative technique

All donor and recipient procedures were performed by the same two teams of surgeon/authors (donors EAP, RLJ and recipients JJP, WDL). Recipients were prepared for surgery in exactly the same manner as our deceased donor recipients. Routine intravenous access and hemodynamic monitoring was employed. A standard right subcostal incision with a vertical midline extension was used in all patients. Recipient hepatectomy was performed without the use of veno-venous bypass or vena cava occlusion at any time.

When the recipient team was ready for the liver graft, the donor was given 5000 units of intravenous heparin prior to the vessels being clamped and divided. The right lobe graft was then procured, weighed and flushed with 2 L of University of Wisconsin (UW) solution. Any ‘backbench’ work including anastomosis of either autologous vein graft or cryopreserved iliac artery allograft to segment V or VIII branches was performed. Immunosuppression was initiated during the anhepatic phase with 1 g of methylprednisolone.

To allow for optimal positioning of the graft relative to the inflow vessels and bile duct, the anterior aspect of the vena cava just below the diaphragm was clamped and opened with a vertical vena cavotomy. End-to-side anastomosis between the right hepatic vein of the graft and the anterior vena cava was performed and provides excellent exposure awhile avoiding the need for cavoplasty or other remedial procedures. At the completion of this anastomosis, the suture was left untied for eventual blood flushing of the graft. In our opinion, this is a helpful step in avoiding venous outflow blockage. During blood flushing, the anastomosis is allowed to expand to its full diameter thus avoiding purse stringing after it is secured.

When inferior right hepatic veins measuring greater than 5 mm were encountered in the donor graft (Figure 1), these were routinely reimplanted in the recipient. Occasionally, significant portions of the anterior segments (V and VIII) of the donor graft drain into the donor middle hepatic vein (MHV) and require reconstruction based on the amount of ‘graft at risk’ for congestion after reimplantation (Figure 1). In no case was the donor MHV taken with the graft. This is somewhat controversial since it is considered critical by some authors (13). When hepatic vein branches draining segments V or VIII into the MHV needed to be reconstructed, anastomosis was performed using either autologous inferior mesenteric vein (IMV) graft or cryopreserved iliac artery allograft from a deceased donor.

image

Figure 1. Hepatic vein territories of a live liver donor using three-dimensional CT renderings. Each color depicts segmental drainage and demonstrates two large inferior hepatic veins draining directly into the vena cava and another draining segment VIII into the MHV. Volume for each segment can be calculated individually to estimate ‘graft at risk’ if not reconstructed. Total estimated graft volumes utilizing virtual resection planes were 90–95% accurate in predicting actual graft volumes. Images were provided by post-imaging software (Hepavision™, MeVis, Bremen, Germany) after ‘rapid slice’ CT scanning.

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Although there is very little data supporting routine reconstruction of segment V or VIII veins that drain into the MHV, the decision to reconstruct these branches was based on the percentage of the graft at risk. If the segment draining into the MHV was greater than 10% of the total graft volume and anticipated loss of liver volume from failing to reconstruct a segment V or VIII branch would lower the graft weight to body weight (GW/BW) ratio <0.8, then routine reconstruction was performed. Brisk visible drainage during back-table flushing with UW solution aided in the decision. Initially, autologous IMV graft was used but due to poor patency we changed our technique to iliac artery allograft for segmental drainage. In some cases, the insertion of the segment VIII branch is close enough to join with the MHV to make a single anastomosis.

During our early experience, only donors with ‘normal’ PV anatomy were considered acceptable. As the program matured, two donors were accepted who presented with a trifurcated PV where the posterior branch of the right lobe inserted into the left branch of the PV. The result is a graft with two PVs oriented vertically. To avoid twisting with PV reconstruction, the native PV bifurcation in the explanted liver was resected on the backbench and reimplanted in the proper orientation.

Hepatic artery reconstruction was performed utilizing 4× loupe magnification with an end-to-end anastomosis between the right hepatic artery of the graft and either the right or left hepatic artery of the recipient. After several failures with hepatic artery thrombosis (HAT) during our early experience, the surgical technique was altered to an all interrupted technique with all suture bites passing from the inside of the vessel to the outside to minimize trauma to the intima. When a graft had a main right hepatic artery and a replaced right hepatic artery, double anastomosis to the recipient left and right hepatic artery was performed. In one case, dissection of the recipient hepatic artery required anastomosis to a loop of redundant splenic artery in an end-to-side fashion for salvage.

Routine intraoperative ultrasound was performed in all cases to confirm excellent blood flow through the graft. In our experience, a palpable thrill in the graft artery is associated with favorable outcome. Any doubt or concern about the arterial inflow of the graft was addressed immediately.

During our ‘early’ experience, 24 of 25 biliary systems were reconstructed using Roux-en-Y hepaticojejunostomy in an antecolic fashion. The antecolic position was used since it allowed for placing radio-opaque markers on the site of the anastomosis if remedial percutaneous radiologic procedures were needed to access the biliary tree. When 3 patients developed colonic dilatation leading to tension on the anastomosis with disruption, all Roux-en-Y limbs were subsequently passed in a retrocolic fashion. This has prevented any further problem with biliary disruption.

During our ‘later’ experience, 23 of 60 (38.3%) recipients underwent choledochocholedochostomy when the graft had a single bile duct. Roux-en-Y hepaticojejunostomy was routinely performed when two or more bile ducts were present or the patient had a diagnosis of primary sclerosing cholangitis (PSC). Biliary stenting with a 5 French pediatric feeding tube placed through the defunctionalized portion of the Roux limb, or cystic duct stump was routinely performed for the purpose of postoperative diagnostic imaging.

Five recipients underwent simultaneous live donor kidney transplantation using a separate live donor. Four of these were primary liver transplants and one case of retransplantation. A separate kidney donor procurement team was used in all cases. Kidney procurement was not initiated until the liver graft was reperfused and the patient stabilized. The kidney graft was placed in the pelvis through a separate incision and the native kidneys were left intact except in one case of oxalosis where both native kidneys were removed prophylactically to decrease oxalate release postoperatively.

Immunosuppression

Since we had initial concerns about the possibility of graft volume loss due to acute cellular rejection (ACR), all recipients received induction immunosuppression (daclizamab 1 mg/kg postoperative day 0 and 4). This was a deviation from our deceased donor recipient protocol since induction therapy is not routinely used. Maintenance immunosuppression regimen was based on tacrolimus or cyclosporin, mycophenolate mofetil (Cellcept™, Roche Laboratories, Inc., Natley, NJ), and a ‘standard’ prednisone taper. Approximately half way through our LDALT experience, a ‘rapid’ (6-week) steroid taper was employed for all recipients.

Preoperative and postoperative imaging

Both donor and recipient liver anatomy and volume were evaluated by multi-phase computed tomography (CT) with three-dimensional renderings (Hepavision™, MeVis, Bremen, Germany). This post-imaging software technology allows for very accurate preoperative total liver and segmental volume assessment, patency of inflow and outflow vessels. Biliary anatomy was defined by CT cholangiography using cholegraffin. Volumetric-CT scans were obtained preoperatively and postoperatively at 1 week, and 3, 6 and 12 months.

Data collection and statistical analysis

Patient demographics, diagnosis, operative data, surgical outcome, liver volume and postoperative complications were prospectively collected and stored in a comprehensive database. Data were analyzed to compare our ‘early’ (first 25) LDALT procedures (December 1998–December 2000) to our ‘Later’ (last 60) cases (January 2001–March 2005) using a statistical software package (SPSS Inc./SYSTAT Software Inc.). Parametric data were compared using analysis of variance (ANOVA). Nonparametric data were compared using chi square. Survival data were analyzed using the Kaplan-Meier method and the log-rank statistic. Statistical significance was set at p < 0.05 for all tests.

Results

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

Influence of program experience

Patient demographics, diagnosis, incidence of hepatocellular carcinoma (HCC), GW/BW ratio, preoperative MELD score, operative data and hospital length of stay (LOS) are presented in Table 1. Comparing our ‘early’ versus ‘later’ experience, only total and warm ischemic times and mean number of readmissions significantly decreased with program experience (Table 1, p < 0.02 by ANOVA). Mean age, sex, body mass index, GW/BW ratio, MELD score, duration of recipient surgery, diagnosis and hospital LOS did not differ significantly between our ‘early’ and ‘later’ experience.

Table 1. Recipient demographics, operative data, and diagnosis stratified by program experience (early: first 25 cases vs. later: last 60 cases)
ParameterEarly experienceLater experienceSignificance
  1. Data presented as mean ± SD; *p < 0.05 versus early group.

Sex (male/female)14/1141/190.174
Age49.0 ± 2.849.4 ± 1.50.897
Body mass index26.2 ± 1.227.3 ± 0.60.381
GW/BW ratio1.3 ± 0.091.2 ± 0.040.162
MELD score15.2 ± 1.118.1 ± 1.00.093
Surgery time (h)6.4 ± 0.45.8 ± 0.20.152
Warm ischemia (h)0.54 ± 0.020.45 ± 0.020.017*
Total ischemia (h)1.0 ± 0.060.9 ± 0.030.015*
Number of readmissions3.1 ± 0.91.3 ± 0.260.012*
Length of stay (days)23.6 ± 4.718.2 ± 2.70.310
Number of bile ducts (1/2/3)15/9/124/30/60.236
Donor procedure time (h)5.4 ± 0.93.9 ± 0.60.001*
Diagnosis (total)25600.525
HCV824 
Cryptogenic38 
ETOH37 
PSC28 
PBC43 
Autoimmune23 
NASH03 
Hemochromatosis11 
Oxalosis10 
HBV10 
Fulminant01 
Alpha 1 ATD01 
Hepatopulmonary01 
Hepatocellular cancer %12300.061

Patient and graft survival

Patient and graft survival were analyzed using the Kaplan-Meier method and log-rank statistic. Survival curves for patient and graft survival are shown in Figure 2A,B respectively. During our ‘early’ LDALT experience, patient survival at 1 year was 70.8% but improved significantly during our ‘later’ experience (92.7%, p = 0.028). Operative (30 days) mortality also significantly improved with program experience (early 16% vs. later 3.4%, p < 0.05 vs. early). Similarly, graft survival at 1 year during our ‘early’ experience was 64% but improved significantly with program experience to 91.1% (p = 0.038). Overall patient and graft survival were not statistically different from our deceased donor experience (patient 92.4%, graft 82.7%) over the same time period. However, ‘later’ LDALT recipients did demonstrate significantly improved patient and graft survival compared to deceased donors recipients over the same time period (Figures 2 and 3, p < 0.05, Cox's F test). At 6 years, there was a trend for improved overall patient survival after LDALT compared to deceased donor recipients (80% vs. 66%, p > 0.05) (Figure 3A).

image

Figure 2. (A) and (B) Kaplan-Meier plots of patient and graft survival stratified by program experience. The ‘early’ experience of 25 cases occurred over the first 2 years of the programs existence between December 1998 and December 2000. The ‘later’ experience of 65 cases occurred between January 2001 and March 2005. Patient and graft survival improved significantly p < 0.05 by log-rank statistic. The number of patients at risk for death each year (years 1–6) were ‘early’ 18, 17, 17, 17, 10, 1 and ‘later’ 46, 31, 23, 5, 0, 0, respectively. The number of grafts at risk over the same time period (years 1–6) were ‘early’ 16, 16, 16, 16, 10, 1 and ‘later’ 46, 41, 23, 5, 0, 0.

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image

Figure 3. (A) and (B) Kaplan-Meier plots of overall patient and graft survival comparing LDALT to deceased donors over the same time period. There was no significant difference between the groups using log-rank statistic. There was a significant difference in patient and graft survival between ‘later’ LDALT (Figure 1A,B) and deceased donor recipients over the same time period (patient p = 0.01; graft p = 0.004, respectively).

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Of the five recipients who underwent simultaneous live donor liver and kidney transplant, all of the patients who underwent primary transplant are currently alive. One patient who underwent retransplant died during the early postoperative period of massive pulmonary embolus leading to cardiovascular collapse.

Complications

There was a trend for less postoperative complications (major and minor) with program experience (early 88% vs. later 66.7%; p = 0.054) but the overall morbidity was 73.8%. Major and minor complication types were stratified by program experience and are shown in Table 2. Of all the complications observed, there was no statistical difference in observed complications with regard to program experience except in the need for retransplant (early 16% vs. later 3.3%, p < 0.05), incidence of early vascular complications (within 7 days) (early, 24% vs. later, 6.7%, p < 0.05), biliary disruption (early, 12% vs. later 0%, p < 0.05), and wound dehiscence (early 8% vs. later 0%, p < 0.05).

Table 2. Observed complications after LDALT
Parameter N (%)Early experienceLater experienceSignificance
  1. *p < 0.05 versus early group; HAT = hepatic artery thrombosis; PVT = portal vein thrombosis.

Overall morbidity (%)22/25 (88)40/60 (67)0.054
Perioperative 30-day morbidity (%)15 (60)28 (47)0.293
Perioperative 30-day mortality (%)4 (16)2 (3.4)0.038*
Vascular complications (%)6 (24)6 (10)0.240
 HAT4(16)5 (8)0.295
 PVT2 (8)1 (1.6)0.213
Postoperative bleeding (%)0 (0)6 (10)0.098
Biliary complications (%)8 (32)23 (38)0.580
 Leak3 (12)13 (21)0.299
 Stricture7 (28)14 (23)0.649
 Recurrent stricture4 (16)2 (3.3)0.038*
 Biliary disruption3 (12)0 (0)0.006*
 Biloma3 (12)3 (5)0.251
 Choledocholithiasis1 (4)2 (3.3)0.662
 Cholangitis7 (28)16 (27)0.934
Bacteremia (%)8 (32)15 (25)0.537
Urosepsis (%)2 (8)2 (3.3)0.364
Require retransplant (%)4 (16)2 (3.3)0.040*
Recurrent HCV (%)2/8 (25)12/24 (50)0.362
Recurrent HCC (%)0/3 (0)3/18 (16.7)0.105
Aseptic bone necrosis (%)2 (8)0 (0)0.280
Compression fractures (%)1 (4)1 (1.7)0.526
Clostridium difficile colitis (%)2 (8)7 (11.7)0.601
Wound cellulitis (%)0 (0)1 (1.7)0.513
Wound infection (%)2 (8)4 (6.7)0.843
Wound dehiscence (%)2 (8)0 (0)0.028*
Incisional hernia (%)2 (8)4 (6/7)0.843
Central pontine myelinolysis (%)0 (0)1 (1.7)0.513
Decubitis ulcer (%)0 (0)1 (1.7)0.513
Evan's syndrome (%)0 (0)1 (1.7)0.513
Guillain-Barre syndrome (%)0 (0)1 (1.7)0.513
Pulmonary embolus (%)1 (4)0 (0)0.122
Peritonitis (%)1 (4)1 (1.7)0.526
Symptomatic pleural effusion (%)1 (4)2 (3.3)0.890
Pneumonia (%)1 (4)6 (10)0.350
Postoperative autoimmune hepatitis (%)1 (4)1 (1.7)0.526
Acute cellular rejection (%)2 (8)2 (3.3)0.364
Small-bowel obstruction (%)1 (4)1 (1.7)0.526
Seizure (%)1 (4)2 (3.3)0.890
Small for size syndrome (%)1 (4)1 (1.7)0.526

Combined biliary complications (disruption, biloma, choledocholithiasis, biliary disruption, bile leakage or stricture) were not influenced by program experience (early 32% vs. later 38%; p > 0.05) or method of reconstruction (Roux-en-Y, 35% vs. duct-to-duct, 40%, p > 0.05). Patients who developed early postoperative leaks tended to develop biloma, strictures, cholangitis or recurrent strictures (Table 2).

Despite a trend for a reduced incidence of HAT with program experience, this did not reach statistical significance (16% vs. 8.3%, p > 0.05). Our current incidence of HAT excluding our early experience is now approximately 5%. HAT and death unrelated to liver disease were the two most common causes of graft loss (30.8% each). However, graft salvage rate in recipients with HAT did improve with program experience (early 25% vs. later 80%). Rapid diagnosis, early return to the operating room for thrombectomy or reconstruction with the use of alternative conduits (splenic, right gastroepiploic or gastroduodenal artery) improved outcome. No interposition vein grafts were used for hepatic artery reconstruction. In two cases, recipients were reexplored for presumed HAT when postoperative day 1 ultrasound failed to confirm intrahepatic flow. Exploration confirmed good flow and palpable thrill in the vessel in both cases. In our experience, rapid return to the operating room is preferable to further radiographic studies or arteriography as it allows for definitive diagnosis and immediate repair if required.

Three cases of complete or partial PV thrombosis were encountered postoperatively in one recipient with a prior transjugular intrahepatic portosystemic shunt (TIPS) and two with preoperative PV thrombosis. In the first, the TIPS was removed from the main PV and it was reconstructed with autologous jugular vein and failed. The latter two cases were partial PV thrombosis identified in the early postoperative period by ultrasound and were taken back to operating room for subsequent thrombectomy before complete thrombosis occurred. In both cases, thrombus was removed from the native PV at the time of transplant prior to reconstruction. These results suggest that only recipients with previous TIPS or PV thrombosis prior to LDALT are at risk for developing PV thrombosis postoperatively.

Based on preoperative imaging, if a right lobe graft was found to have either segment V or VIII that was greater than 10% of total graft volume with a hepatic vein branch that drained into the MHV, and failing to reconstruct these branches would leave a graft smaller than 0.8% graft weight to body weight ratio, we would consider this a ‘graft at risk’. Using these criteria, reconstruction of segment V or VIII branches with either autologous IMV graft or cryopreserved iliac artery allograft was performed. In this study, only 12% (n = 10) of donors had segment V or VIII branches that required reconstruction (10/85) based on these criteria and is not dissimilar to other series (14). Regardless of the technique used, all but one reconstructed segment V or VIII branches thrombosed by 3 months postoperatively. Six were reconstructed with autologous IMV graft and four with cryopreserved iliac artery allograft. All of the IMV grafts thrombosed by 1 week postoperatively with only two iliac artery allografts remaining patent for 1 month and one for 3 months. In one case, dehydration from a gastrointestinal illness may have contributed to iliac artery allograft thrombosis in a recipient who had a patent conduit draining segment VIII based on imaging at 3 months postoperatively but shortly thereafter developed transient significant elevations in liver enzymes and reimaging confirmed thrombosis. No grafts were patent beyond 4 months postoperatively. Given the rapid rate of liver regeneration, temporary patency may provide some protection from early graft congestion. Low flow rates, technical failures and rotation of graft during regeneration may be the predominant mechanisms resulting in segmental graft thrombosis. Cryopreserved iliac artery allograft demonstrated slight improvement in short-term patency but it is unclear that this can justify the significant extra cost associated with these arterial grafts.

Biopsy proven ACR was 4.7% for all patients in this series. This compares to approximately 30% in our deceased donor population. Initiating a ‘rapid’ (6-week) steroid taper did not alter ACR rates in our ‘later’ series. Short ischemic times, improved graft quality and more aggressive immunosuppression may explain some of the differences observed between our LDALT and deceased donor recipients.

Liver regeneration

Recipient liver volume rapidly adjusted to 100% of standard liver volume (SLV) within 1 month post-transplantation (15). Liver grafts less than 100% SLV demonstrated rapid regeneration. In two children who received right lobe grafts approximately 120% of their SLV, volumetric CT scans demonstrated atrophy over the same time period with plateau at 100% SLV.

Discussion

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

There has been increasing concern that adult to adult live donor liver transplantation does not afford recipients the same survival and outcome as those achieved with deceased donors whole liver grafts (4,5). As with any surgical innovation, program and surgeon experience improves outcome over time. ‘Experience’ is the acquisition of knowledge from active participation in events and the concept of improved outcome with LDALT after a ‘learning curve’ experience is well established (16,17). In this article, we analyze our program changes and experience as they relate to recipient outcome.

The decision to analyze our data using 25 cases as the break point between our ‘early’ and ‘later’ experience was somewhat arbitrary. Others have suggested that their learning curve experience was approximately 20 cases (18). The recent adult to adult living liver (A2ALL) transplantation study also has suggested that programs that have performed less than 20 live donor procedures were more likely to experience poor outcome (19). In this series, the first 25 cases were performed during the initial 2-year period of the live donor liver transplant program at the Lahey Clinic. During that time period, several modifications in the program were implemented and improved technologies became available. The surgical technique in both donors and recipient was modified and improved. In short, after that initial 2-year period, we felt that the program had matured and that the team had achieved an adequate level of ‘field strength’ as eloquently described by the late Dr. Francis D. Moore in discussing the ethics of medical and surgical innovation (20). The following are the elements in our program and operative technique that we believe have contributed to improved outcome in LDALT recipients.

First, recipient selection was refined when it was realized that patients who were more debilitated, suffered significant malnutrition and had significant portal hypertension were more likely to experience ‘small for size syndrome’ than those with well-compensated liver failure (21). In this respect, MELD score does alone not take into consideration other comorbidities that may also predict poor outcome (22). While we have successfully performed LDALT in patients with very high MELD scores in the setting of fulminant hepatic failure, the absence of significant portal hypertension along with relatively low blood loss (<10 units) during those procedures contributed to favorable outcome. Our current practice is to consider LDALT in patients with MELD scores that are likely to benefit from transplantation (i.e. >15) (9) while being more cautious when the unadjusted MELD scores are above 30 (23). There are no absolute contraindications for LDALT based on MELD score since some patients with lower MELD scores may have had life threatening events (variceal bleeding) or suffer from inadequate quality of life that increases the desire to proceed with transplantation. Obviously, the decision to proceed with LDALT is complicated and is dependent on many interrelated variables between donor and recipient and is impacted by the availability of deceased donor organs and waiting list mortality (24).

Secondly, a competent, comprehensive and independent medical evaluation of each donor has had the positive effect of improving donor safety while providing the best possible graft for the recipient. Undiagnosed medical illnesses such as renal cell cancer, liver disease, diabetes, hypertension, coagulopathy were just a few of the problems identified in so-called ‘healthy’ donors. The medical evaluation of donors has been expanded to routinely screen for hypercoaguable states after a recipient with homozygote Factor V Leiden received a graft obtained from a heterozygote Factor V Leiden donor developed complete graft thrombosis while on therapeutic heparin and warfarin. Factor V Leiden in the donor and recipient is now an absolute contraindication for LDALT in our practice.

Major advances in imaging technology with segmental volume assessment have resulted in better identification of suitable donors in terms of graft size and has aided in the development of the concept of ‘graft at risk’ from segment V and VIII hepatic vein branches. Recently, the addition of a biliary contrast agent to the volumetric CT scan has allowed for simultaneous noninvasive assessment of the donor biliary anatomy thus avoiding the need for preoperative or invasive biliary imaging in the donor.

The addition of more precise post-imaging software technology has also allowed for adequate surgical planning when considering donors with more complicated anatomy. Initially, higher risk donors with complicated PV anatomy and marginal liver size were avoided to maximize donor safety and to simplify the recipient procedure. With more experience, more complicated donor anatomy was considered acceptable, such as those with trifurcated PVs (right posterior PV originates from the left PV). While many operations are technically feasible, it may not be reasonable to attempt these more difficult situations until the team has achieved adequate ‘field strength’.

Another technical modification in the donor operation that has improved recipient outcome was achieved by standardizing the liver parenchymal transection. After a trial of various surgical techniques and instruments used for dividing the liver, we have found that the water hydro-jet dissection technique superior and more rapid in most cases. The hydro-jet device has helped to minimize graft injury and the zone of necrosis along the transection line compared to other techniques. Donor operative times have steadily and significantly decreased as well (5.4 h ‘early’ vs. 3.9 h ‘later’, p < 0.001, Table 1). Other techniques using bipolar electrocautery alone can result in a larger zone of necrosis. In one case where a ‘floating ball’ electrocautery device was used, a 2 cubic centimeter area on the cut surface of the right lobe liver graft was lost contributing to the development of ‘small for size syndrome’.

Not surprisingly, it has become clear that the success of the recipient procedure was not only dependent on the quality of the recipient operation but also on the quality of the donor evaluation and graft procurement. As results steadily improved, it was felt that consistency of the surgical team was a positive influence and should not be changed to avoid secondary learning curves.

Biliary problems continue to be the most common complication after LDALT and were not influenced by program experience or method of reconstruction. Investigation of the literature suggests that the rate of biliary complications ranges widely but has persisted despite various reconstructive techniques with or without the use of stents. Biliary complications are related to multiple factors and not surgical technique alone. Therefore, attempts to identify donor features (number of bile ducts, arterial blood supply to the right hepatic duct, etc.) may provide clues as to how to reduce biliary complications after LDALT. Ultimately, better donor selection with favorable anatomic features may be the best strategy for avoiding biliary complications.

Another area of concern and surgical debate is the issue of maximal venous outflow and the best method for surgical reconstruction to avoid graft congestion. Three surgical techniques for maximizing venous outflow have evolved. These include, (i) including the MHV with the donor graft in all cases, (ii) selectively reconstructing larger segment V and VIII venous tributaries draining to the MHV or (iii) performing remedial backbench procedures to create ‘cloacae maximum’ to augment drainage (13,25).

Since donor safety was paramount, our program made a decision to not include the MHV with the donor graft. This decision has not compromised surgical outcome or increased the incidence of ‘outflow block’. Patients with severe portal hypertension and higher MELD score may benefit from routine inclusion of the MHV to increase graft size since this technique can also be performed safely (13).

The superior patient and graft survival observed after LDALT in our later experience compared to deceased donors deserves comment since it differs from other published reports (4). We are unable to identify a single reason for these results. Differences in survival are not related to diagnosis, patient demographics or incidence of HCV and HCC, which are similar to our deceased donor recipients (Table 2). However, some of the following parameters may have contributed to improved results after LDALT since they differ from our deceased donor recipient population.

First, recipients of live donor grafts in this series had MELD scores approximately one-half of those observed in our deceased donor recipients during the same time period. While outcome after LDALT was not influenced by preoperative MELD score other series (26), live donor recipients with lower MELD scores generally present with improved nutritional status and metabolic reserve, which may improve outcome (27).

Relatively short ischemic times (1 h) were observed in our LDALT group and this improved significantly with program experience (0.9 h, Table 1). These ischemic times are significantly shorter than those observed with our deceased donors that typically range between 4–12 h. Short ischemic times, undoubtedly, reduce the incidence of early and late postoperative complications after LDALT (28–31) and may explain in part the reduced incidence of ACR after LDALT in this series (32). More aggressive immunosuppression with induction therapy may have also played a role. Rapid steroid taper over 6 weeks was well tolerated and did not alter outcome.

Another important issue is graft quality. Graft quality from living donors is excellent if procurement is properly performed. Live donors are usually young, healthy and have ‘normal’ liver function. This affords the live donor recipient an advantage over the deceased donor recipient since the national organ shortage has resulted in the use of donors after cardiac death and ‘marginal’ donors which may be inferior (33–35). While graft quality is important during liver transplantation, the contribution of an experienced hepatobiliary surgeon in preserving graft integrity during live donor liver procurement is unquantifiable but undoubtedly paramount to favorable outcome.

In regions of the country such as ours, where waiting list mortality can exceed 20%, LDALT provides a suitable alternative for patients with end-stage liver disease. This study demonstrates that excellent results can be achieved with LDALT using right lobe grafts despite a high morbidity rate. In our experience, simplifying the surgical technique as much as possible has proven to be advantageous for both the patient and the operative team. Comprehensive medical and anatomic evaluation of the donor avoids ‘surprises’ and provides the recipient with the best possible graft. Continuing efforts to identify donor features that contribute to the pathogenesis of recipient complications will improve safety and surgical outcome.

Acknowledgments

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

This work was supported in part by unrestricted educational grant from Roche Laboratories, Inc. and the Robert E. Wise Educational Foundation of Lahey Clinic Medical Center.

References

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