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Functional analysis of grafts from living donors. Implications for the treatment of older recipients
J C Emond1, J F Renz, L D Ferrell
1Department of Surgery, University of California, San Francisco, USA.
Insights
Living-related liver transplantation (LRLT) using small grafts in adult recipients leads to significant dysfunction and graft injury. Careful consideration of graft size is crucial for successful LRLT outcomes.
Area of Science:
- Hepatology
- Transplant Surgery
- Gastroenterology
Background:
- Living-related liver transplantation (LRLT) is effective in children, but its application in larger recipients necessitates smaller grafts due to donor hepatectomy limitations.
- The optimal minimum graft weight for successful LRLT remains undefined, with observed dysfunction in patients receiving small grafts.
Purpose of the Study:
- To investigate the clinicopathologic features and outcomes of small liver grafts in living-related liver transplantation.
- To compare graft function and histology between small and adequate-sized grafts in LRLT recipients.
Main Methods:
- A retrospective analysis of clinical and histologic data from 25 LRLT patients.
- Patients were divided into a small group (graft ≤50% of expected liver weight, n=5) and a large group (graft ≥60% of expected liver weight, n=20).
- Graft function was assessed through clinical parameters and liver biopsies.
Main Results:
- Graft loss occurred in 40% of the small group versus 10% in the large group; one death in the small group.
- The small group exhibited significantly decreased early function (prothrombin time on day 3) and cholestasis (bilirubin levels on days 7 and 14).
- Histology in the small group showed ischemic changes and cellular ballooning, progressing to cholestasis, while the large group had minimal ischemic changes.
Conclusions:
- Small-for-size liver grafts in LRLT are associated with significant functional impairment and ischemic-related histologic changes.
- Graft injury in these cases is directly linked to the small graft size.
- Findings highlight the challenges and implications of extending LRLT to adult recipients using small grafts.
Objective:
Living-related liver transplantation (LRLT) has established efficacy in children. In a larger recipient, LRLT requires the use of a small graft because of limits on the donor hepatectomy.
Summary Background Data:
The minimum graft weight required for successful transplantation has not been well established, although a characteristic pattern of graft dysfunction has been observed in our patients who receive small grafts. The authors present a clinicopathologic study of small liver grafts obtained from living donors.
Methods:
Clinical and histologic data were reviewed for 25 patients receiving LRLT. In five older recipients (small group), the graft represented 50% or less of expected liver weight, whereas in 20 others (large group), the graft represented at least 60% of expected liver weight. A retrospective analysis of graft function was conducted by analyzing clinical parameters and histology.
Results:
In the small group, 2 of 5 grafts (40%) were lost due to poor function, leading to one patient death (20% mortality), whereas in the large group, 2 of 20 grafts (10%) were lost due to arterial thrombosis without patient mortality. Early ischemic damage related to transplant was comparable with aspartate aminotransferase 203 +/- 23 (small group) and 290 +/- 120 (large group) at 24 hours (p = not significant). Early function was significantly decreased in the small group, with prothrombin time 18.2 +/- 2.2 seconds versus 14.8 +/- 1.6 seconds (large group) on day 3 (p = 0.034). All small group patients developed cholestasis with significantly increased total bilirubin levels at day 7 (16 +/- 5.2 mg% vs. 3.7 +/- 2.7 mg%; p = 0.021) and day 14 (12.0 +/- 7.4 vs. 1.8 +/- 0.7; p = 0.021) compared with the large group. Protocol biopsies in the small group revealed a diffuse ischemic pattern with cellular ballooning on day 7, which progressed to cholestasis in subsequent biopsies. Large group biopsies showed minimal ischemic changes. Three small group patients recovered with normal liver function by 12 weeks.
Conclusions:
Clinical recovery after a small-for-size transplant is characterized by significant functional impairment associated with paradoxical histologic changes typical of ischemia. These changes apparently are due to graft injury, which can only be the result of small graft size. These findings have significant implications for the extension of LRLT to adults.