Difference Between LDLT and DDLT in Predicting Early Graft Function

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Li et al1 proposed a model characterizing early allograft dysfunction (EAD) in patients after living donor liver transplantation (LDLT), based on data from 2944 patients worldwide. This model is expected to make LDLT safer and more effective by selecting live donors based on the recipient’s possible postoperative course. Li et al adopted the definition of EAD as specified by Olthoff et al2: total bilirubin ≥10 mg/dL or prothrombin time and international normalized ratio test 1.6 on day 7, or alanine transaminase/aspartate transaminase >2000 U during the first week posttransplant. Furthermore, this study identified the following as independent predictive factors for EAD: Laboratory Model for End-Stage Liver Disease (MELD) score, necessity for hospitalization at the time of transplant, and graft weight. A diagnosis of EAD does not always result in early allograft failure. Therefore, predicting EAD should not be the sole criterion for deciding the indication for LDLT but rather a preliminary estimate of the possible postoperative course of the disease, which may allow for a detailed treatment strategy, including donor characteristics. Li et al observed a 5-y overall survival of 70.6% among patients who developed EAD after LDLT, which was significantly lower than among those without EAD; however, this outcome is an appropriate basis for considering LDLT to be an effective treatment. As discussed by the authors, the survival curve for patients with EAD declines steeply from 3 to 6 mo posttransplant. However, beyond this period, the survival curve for the EAD group was parallel to that of the non-EAD group, indicating that similar long-term survival rates can be achieved in patients who have recovered from EAD. Previous studies have shown that smaller grafts are associated with unfavorable outcomes in patients who are severely ill.3 For those with high MELD scores, for example, it is widely known that donor age and graft volume are important considerations in donor selection.4,5 The major difference between deceased donor liver transplantation (DDLT) and LDLT is that owing to partial liver use, LDLT carries an increased risk of small-for-size graft syndrome (SFSS). We previously reported that MELD score and donor age were associated with the occurrence of postoperative SFSS in patients with an undersized grafted donor liver, particularly those resulting in a graft-to-recipient weight ratio (GRWR) <0.6%.6 Posttransplant survival was significantly decreased in patients who experienced SFSS compared with those who did not. In the study by Li et al, graft weight was found to be a predictor, however, GRWR and graft volume/recipient standard liver volume ratio were not. The definition of EAD used in the study by Li et al was the same as that used in DDLT. The total bilirubin and prothrombin time values included in the definition of EAD described above are used in the definition of SFSS after LDLT.7,8 Although SFSS is associated with a poor prognosis, the prognosis is not always poor in patients with elevated bilirubin levels but normal prothrombin levels, a condition known as preserved synthetic capacity.4 An analysis of 10 000 cases (pediatric, n = 3572; adult, n = 6428) of LDLT based on recipient data obtained from the Japanese Liver Transplantation Society registry showed that the following were significant prognostic factors for long-term patient survival in adults: GRWR <0.6, donor age older than 60 y, recipient age older than 60 y, MELD score, and center volume.9 Among adult recipients aged 50–60 y, early patient survival and graft survival up to 5 y were significantly better in cases with a GRWR ≥0.7 than in those with a GRWR <0.7. (P = 0.02). The results of this registry-based study clearly showed the importance of combining recipient and donor conditions to ensure favorable posttransplant outcomes. Therefore, the outcomes based on actual data from the Japanese registry were consistent with the predictive factors of EAD described in the study conducted by Li et al. In this study, Li et al assessed the degree of macrosteatosis through pretransplant imaging, as liver biopsy is not recommended owing to its invasiveness. However, because pretransplant imaging does not necessarily reflect actual steatosis, an analysis of the findings of a time-zero biopsy of the transplant grafts may offer additional information regarding expected postoperative results. However, if an association between the grade of steatosis and EAD is confirmed, a less invasive, yet accurate, preoperative assessment of liver steatosis through various tools, including imaging evaluations, would be clinically useful for donor selection when used in conjunction with the recipients’ condition.10 Although graft weight has been clinically identified as a predictor of EAD by Li et al, it is important to evaluate grafts comprehensively, including various characteristics such as weight, age, grade of steatosis, and the volume of the congestion zone associated with the graft type. Furthermore, this study demonstrated that graft weight is a prognostic factor. However, unlike GRWR and graft volume/recipient standard liver volume ratio, graft type cannot be determined without knowing the relationship between graft weight and recipient body size, making it difficult to envision the usefulness of this factor in the clinical setting. Although the study by Li et al was a multicenter study based on global data, it is difficult to determine the clinical significance of graft type based on weight alone, given the size differences between Western and Asian individuals. The pathogenesis and dynamics of EAD vary between LDLT and DDLT. Considering the indications for LDLT, a specific definition of EAD as pertains to the clinical outcomes of the procedure is needed. However, even if it does not directly lead to survival, the preoperative prediction of EAD based on the current definition may lead to more personalized and appropriate postoperative management. Additionally, preoperative EAD prediction may assist in decision-making for patients and their families by informing them of possible postoperative courses. The primary achievement of the study by Li et al was the creation of a reliable tool for predicting EAD based on data from multiple centers worldwide. If a definition of EAD that has a stronger association with prognosis is established on the basis of the characteristics of LDLT, it is expected that the creation of a tool using the same methodology described by Li et al would enable more detailed treatment strategies and lead to safer and more effective LDLT.

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