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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.
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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.