Health & Medical Organ Transplants & Donation

Complications of Living Donor Hepatic Lobectomy

Complications of Living Donor Hepatic Lobectomy

Discussion


In 2008, we reported that in a retrospective cohort of 396 LLD (387 right and 9 full left lobes), 38% developed at least one complication, the vast majority within the first year. In 2010, the Toronto group reported that in a retrospective single center experience of 202 right lobe donors with a minimum follow-up of 12 months, 40% developed complications within the first year. Also in 2010, the Kyoto group updated their previously published experience with LLD complications. A retrospective single-center review of 500 right lobe donors with a median follow-up period of 36.5 months revealed that 44% experienced at least one complication within the follow-up period. In the current study, we have markedly extended the duration of follow-up in the retrospective era donors and include an additional 352 donors whose procedures occurred in the prospective era. In total, this represents the complete experience with LLD at these nine centers over a nearly 12-year period. We now report that among 740 LLD (707 right lobes), 39% developed at least one complication in the first year, an incidence strikingly similar to and confirming our prior experience and that of others. We have also confirmed that increasing center experience is not associated with a reduction in donor complications. Therefore, we propose that 40% can be considered a fairly definitive assessment of the risk of complications in the first year following live donor right lobectomy. Regarding the severity of these complications, we had previously reported that 2.8% of patients had Clavien grade 3 or 4 complications. Using a slight modification of the Clavien classification in which grade 4 included residual disability or death, the Toronto group reported that out of 202 donors, 15.8% of patients had a grade 3 and none had a grade 4 complication. The Kyoto group, using a 5-tier modification of the Clavien system, reported that in 500 LLD (right lobe), 17% developed >grade 3 complications (consistent over 3 eras) with 1/500 grade 5 (death). Using the same grading system, the Pittsburgh group reported that among the 121 LLD (right lobectomy), 10.7% of patients developed >grade 3 complications (no grade 5). Our current combined A2ALL study shows that 8/740 LLD (1.1%) developed a grade 3 (residual disability, n = 5) or grade 4 (liver failure or death, n = 3), 7/396 (1.8%) in the retrospective era and 1/344 (0.3%) in the prospective era. The Kyoto and Pittsburgh groups used versions of the Clavien system that did not specifically capture residual disabilities. Based on the Toronto and A2ALL experience, the combined risk of residual disability, liver failure or death following LLD (0/202 and 8/740, respectively), is approximately 1%. We have previously defended our use of the 4-tier Clavien system. Our current study also demonstrates that 20/760 (2.6%) procedures were aborted intraoperatively (2.9% and 2.3% in retrospective and prospective cohorts prospectively). The Toronto group has reported 4.9% (12/252) aborted procedures. Thus, we consider that 2%–5% represents the risk of aborted LLD.

A major aim of our study was to evaluate predictors associated with postdonation complications. The Pittsburgh group identified BMI ≥ 30 and macrovesicular steatosis as significant risk factors for the development of grade 4a complications. The Kyoto group found donor age and prolonged operative time to be associated with any complication and with biliary complications, but gender, BMI, and blood loss were not significant risk factors in a limited analysis. We now confirm our previous observation, that blood transfusion is associated with a significantly higher risk of complication, and specifically of bile leaks and infection. In our current study, each unit of transfused blood was associated with a 38% to 55% higher risk of complication. Intraoperative hypotension (systolic blood pressure <100 mm Hg) was associated with an overall higher risk of complications, independent of the requirement for blood transfusions. Donors with higher body weight were at significantly higher risk of bile leak; each increment of 10 kg in body weight increased the risk by 22%. Risk factors for incisional hernia formation included older age, male gender and higher BMI, each of which has been observed in populations of general surgical patients undergoing open abdominal procedures. Baseline predonation laboratory studies have had inconsistent associations with donor complications. In the current study, we failed to confirm our prior finding that higher levels of alkaline phosphatase were associated with a higher risk of complications. However, higher predonation serum bilirubin was surprisingly associated with a lower risk of development of complications. As with alkaline phosphatase, the vast majority of serum bilirubin levels fell within the normal range. A biological basis for these associations is not obvious.

Previous studies have focused principally on the development of complications within the first year following donation. We had previously reported that 46% of all complications occurred during the initial hospitalization. The Toronto group focused their analyses on complications within 30 days of donation and between 30 days and 1-year postdonation, but noted one keloid, one incisional hernia and one bowel obstruction that presented between 1 and 5 years postdonation. The Pittsburgh group did not report long-term complications. The Kyoto report spanned three empirical eras but made little attempt to analyze long-term complications. Our current study demonstrates that certain complications (hernia, bowel obstruction and psychological complications) may develop as late as 5 or more years after donation. A novel feature of the current report is the analysis of the time to resolution of postdonation complications, starting from their time of onset. Nearly 80% of complications resolved by 3 months. However, some complications took many years to resolve or remained unresolved as long as 3 to 5 years after presentation. The probabilities of resolution by 1 year after diagnosis were only 75% and 42% for hernias and psychological complications, respectively. This is especially important since these same types of complications tended to occur later postdonation. In contrast, neuropraxia, which developed immediately after donation, took as long as 3 years to resolve. Of interest, with longer follow-up, some complications initially defined as Clavien grade 3 (residual disability at the time of recording) eventually resolved and were downgraded to 2, explaining the discrepancy in the number of grade 3 complications between our previous and current reports. This was true for several cases of neuropraxia. The exact proportion of grade 3 complications that eventually resolve over time and are therefore downgraded to grade 2 is unclear, and while this may add confusion to the assessment of donor morbidity, it highlights the need for longer term follow-up and underlines the significance of the current study. We did not observe any examples of upgrading over time.

We should note that since the current analysis, two well publicized donor (right lobectomy) deaths have occurred in the US. One of these occurred at a center that participated in the A2ALL study, on which we currently report, but the study was closed for enrollment at the time of donor death and therefore it is not included in the analysis. The other donor death occurred at a nonparticipating center. Both centers were among the most experienced adult LLD in the US at the time of these events. Therefore, although not part of our analysis, we believe that these deaths warrant mention to prevent an erroneous interpretation of a decrease in grades 3 and 4 complications between the retrospective and prospective cohorts.

Limitations of our study include limited data for some donors who may have sought treatment elsewhere, and the possibility of under-ascertainment of retrospectively assessed complications. Although we collected data on 29 specific complications generated by consensus among the study investigators, we did not include an 'other' category for rare or unexpected complications. All centers were monitored annually, but only approximately 10% of records were audited for accuracy of reporting. Over the course of the study, these audits uncovered a few new complications, suggesting that complications may be slightly underestimated. In addition, the exact nature of donor work up was not prescribed by the study and it is certainly possible that participating centers used varying inclusion and exclusion criteria for donors, and that these may have changed over the period of study. Finally, our observations regarding the relative risk of complications for left versus right lobe donation are inconsistent with that of others, most likely as a result of the small number of left lobe donors in our cohort. We believe that all the limitations described above could have only a modest effect on our results.

From this longitudinal observational cohort of 740 completed hepatic lobe donations in the multicenter A2ALL consortium, we can draw several important conclusions: (1) the incidence and severity of LLD complications are well defined and do not appear to change over time (40% overall incidence of complications, 1% incidence of residual disability, liver failure or death and 2%–5% risk of aborted donation); (2) there do not appear to be any significant risks associated with LLD complications not previously identified; (3) the impetus to further compile and register LLD complications specifically for the purpose of assessing general donor risk should take into consideration our first two conclusions. We believe that any further investigation should focus on assessing the relative risk of evolving LLD approaches that may alter the risk profile and (4) we have found that longer follow-up (>1 year) allows for a better understanding of the natural history of LLD complications, including late complications and time to resolution. Therefore, we believe that the current study will serve as a comprehensive report to inform decision making by potential donors and their caregivers, and as a benchmark against which the effectiveness of future interventions or strategies to reduce donor complications can be measured.

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