Evaluation of donor steatosis in living donor liver transplantation

Abstract

Donor evaluation forms the cornerstone of safe and successful living donor liver transplantation (LDLT). It aims to both identify a suitable graft for the recipient and protect the donor from unnecessary surgical risk of donor hepatectomy. The process and outcomes of donor evaluation have evolved over the past few decades and will likely continue to evolve in the future, as ongoing efforts aim to safely widen the donor pool and expand the applicability of LDLT. One important challenge for future donor evaluation is the rising prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), as careful assessment of hepatic steatosis is required to safeguard donor safety. In this thesis, the outcomes of donor evaluation in the past were reviewed, including the reasons for donor non-acceptance and the changes that have occurred over time. Additionally, the use of computed tomography (CT) and transient elastography (TE) for non-invasive assessment of hepatic steatosis in donor candidates were examined. To determine donor evaluation outcomes, a retrospective study involving 2035 donor candidates evaluated from 1997-2020 was conducted. Comparison was made between donor evaluation outcomes in 1997-2008 and 2009-2020. The overall donor acceptance rate was 40.1% and it decreased in the recent decade (44.8% vs. 38.0%, P=0.002). Fewer candidates were declined due to ABO incompatibility (26.7% vs. 13.5%, P<0.001) and viral hepatitis (17.5% vs. 5.5%, P<0.001), while a higher prevalence of metabolic syndrome (4.4% vs. 16.7%, P<0.001), cardiac disease (0.7% vs. 5.7%, P<0.001), malignancy (0.5% vs. 2.3%, P=0.016) and psychological contraindications (22.8% vs. 39.6%, P<0.001) were observed. Technical contraindications contributed to only 5% of donor nonacceptance. The study also investigated donor-recipient relationships, revealing a decrease in offspring (22.6% vs. 12.9%, P<0.001) and partners (25.7% vs. 15.0%, P<0.001) and an increase in friends (5.6% vs. 8.8%, P=0.007) and Samaritan (0.1% vs. 11.1%, P<0.001) donor candidates. The majority of recipients only had one potential live donor available. Donor candidates with hepatic steatosis ≥10% are currently declined for donation. In view of the growing prevalence of hepatic steatosis among donor candidates, there is an unmet need to develop non-invasive assessment modalities to evaluate donor hepatic steatosis and minimise the reliance on invasive pre-donation liver biopsy. To address this need, a retrospective study was conducted involving 67 donor candidates who underwent pre-donation liver biopsy and CT scan of liver. Non-contrast CT-derived hepatic attenuation, among other parameters, was found to have good diagnostic performance in predicting steatosis ≥10% on histology (AUC 0.833, P<0.001). A prospective study involving 83 donor candidates was commenced to investigate the diagnostic performance of TE and compare it with CT. The study found that 36.1% of donor candidates had mild to severe hepatic steatosis, as assessed by TE with controlled attenuation parameter (CAP). Among the 37 candidates with either pre-donation liver biopsy or intraoperative graft biopsy available, CAP showed good diagnostic performance in predicting hepatic steatosis ≥10% on histology (AUC 0.811, P<0.001), but CT-derived hepatic attenuation parameters did not perform as well (AUC 0.423-0.427). The results suggested that TE alone or in combination with CT can potentially minimise or replace the need for liver biopsy. Further studies with larger study cohorts are needed to fully validate the use of TE in reliably assessing hepatic steatosis in living donor evaluation.