Liver regeneration after living donor transplantation: Adult‐to‐adult living donor liver transplantation cohort study

Abstract

Background & Aims Adult-to-adult living donors and recipients were studied to characterize patterns of liver growth and identify associated factors in a multicenter study. Methods 350 donors and 353 recipients in A2ALL (Adult to Adult Living Donor Liver Transplantation Cohort Study) transplanted between March 2003 and February 2010 were included. Potential predictors of 3-month liver volume included total and standard liver volumes (TLV, SLV), the model for end-stage liver disease (MELD) score (in recipients), remnant and graft size, remnant to donor and graft to recipient weight ratio (RDWR, GRWR), remnant/TLV, and graft/SLV. Results Among donors, 3-month absolute growth was 676±251g (mean± SD) and percent reconstitution was 80%±13%. Among recipients, GRWR was 1.3%±0.4% (8<0.8%). Graft weight was 60%±13% of SLV. Three-month absolute growth was 549±267g and percent reconstitution was 93%±18%. Predictors of greater 3-month liver volume included larger patient size (donors, recipients), larger graft volume (recipients), and larger TLV (donors). Donors with the smallest remnant/TLV ratios had larger than expected growth, but also had higher postoperative bilirubin and international normalized ratio at 7 and 30 days. In a combined donor-recipient analysis, donors had smaller 3-month liver volumes than recipients adjusted for patient size, remnant or graft volume, and TLV or SLV (p=0.004). Recipient graft failure in the first 90 days was predicted by poor graft function at day 7 (HR=4.50, p=0.001), but not by GRWR or graft fraction (p>0.90 for each). Conclusions Both donors and recipients had rapid yet incomplete restoration of tissue mass in the first 3 months, confirming previous reports. Recipients achieved a greater percentage of expected total volume. Patient size and recipient graft volume significantly influenced 3 month volumes. Importantly, donor liver volume is a critical predictor of the rate of regeneration, and donor remnant fraction impacts post-resection function.

Hepatic Hemodynamics and Portal Flow Modulation

“…While portal overflow injures the liver directly through nutrient excess, 17,21,22 endothelial activation 21 , and sinusoidal shear stress 19,23,24 , arterial vasoconstriction introduces secondary ischemic damage 25,26 . Several lines of work indicate that these insults are attenuated by reduction of portal flow.…”

“…When we examined the effects of modulation on the incidence of graft dysfunction (using the A2ALL definition 19 ), we noted that the modulated livers had an increased incidence of graft dysfunction consistent with the high frequency of left lobes and small grafts in the modulated population. A predictive model for the development of graft dysfunction identified modulation, left lobe, bilirubin, and donor age as predictors.…”

“…The occurrence of graft dysfunction was defined using criteria previously reported 19 derived from A2ALL-1 data based on postoperative day 7 lab values. Graft failure was defined as the earlier of retransplant or death.…”

Ad Integrum Functional and Volumetric Recovery in Right Lobe Living Donors: Is It Really Complete 1 Year After Donor Hepatectomy?

“…Contrary to findings in other studies (20,32,37) [14,18]), and also during the first month, (RLL/TLV ranged from 64% to 89% [25,30,33,49], and mean liver growth from 115% to 181% [14,25,27]). After the initial month, the rate of regeneration slowed down, RLL/TLV reaching 74-80% (33,38,40,53), 72-96% (17,23,29,31,37,46,(51)(52), and 80-97% (16,23,26,29,31,33,40,53) in the first 3 months, 6 months, and 1 year, respectively, after donor right hepatectomy. In our study, liver volume increased to more than 2Â estimated remnant liver volume at the end of 1 year, yet ad integrum liver regeneration did not occur.…”

“…Our study is one of the first to objectively demonstrate this fact. Only three other studies used paired sample t-test (27,36,53) to analyze the ad integrum restoration of liver function tests. They also found that ad integrum recovery does not occur even up to 1-2 years after donor hepatectomy.…”