Female-to-Male Match Predicted Poor Survival After Living-Donor Liver Transplantation—Some Issues Needed to be Clarified

Abstract

We read with great interest the recent article by Yoshizumi et al. (1), which evaluated the risk factors that increased mortality after living-donor liver transplantation. Their study found that male recipients of transplants from female donors (FM), those having pretransplantation diabetes mellitus (DM), and having a model for end-stage liver disease score of 20 or more were independent risk factors that predicted poor survival for LDLT recipients. Nevertheless, close inspection of the study revealed some methodological issues that are worth mentioning and clarifying. First, Yoshizumi et al. (1) reported 335 cases of living-donor liver transplantation (LDLT), which included 180 cases of benign end-stage liver diseases and 155 cases of hepatocellular carcinoma (HCC). HCC accounts for nearly half of the cohort patients, and HCC recurrence is the main cause of death in the study (14/80). However, none of the risk factors that increased mortality after LDLT in the study, to our knowledge, is related to HCC recurrence. Tumor recurrence is the main cause of death after liver transplantation for HCC, as demonstrated by previous studies (2, 3). Not surprisingly, some factors associated with biologic aggressiveness, such as tumor number, tumor differentiation grade, presence of a peritumoral capsule, and microscopic vascular invasion, were independent predictors of survival (4–7). In other words, tumor biology determines outcome after liver transplantation for HCC, whereas for benign end-stage liver diseases, the factors that predicted survival were model for end-stage liver disease scores and Child-Pugh category (8–10). Recently, Li et al. (11) reported that preoperative renal dysfunction, intraoperative red blood cell transfusions of greater than 5 U, and female-to-male gender match were independent risk factors that predicted poor survival for LDLT recipients with benign end-stage liver diseases. Therefore, it is not very proper to analyze the factors that predicted poor survival of LDLT recipients, which were mixed by benign end-stage liver diseases and HCC. The authors should separately analyze the factors that predicted survival of LDLT for HCC and benign end-stage liver diseases. Second, the authors reported that the 1-year, 3-year, and 5-year survival rates after LDLT for HCC were 91.7%, 80%, and 69%, whereas rates for benign end-stage liver diseases were 80.5%, 74.7%, and 73.0% (in Table 2 of Yoshizumi et al. (1)). Patients in the HCC group showed higher 1-year, 3-year, 5-year survival rates compared with patients in the benign end-stage liver diseases group, although this difference was not statistically significant (P=0.077). Did the authors consider that the long-term survival rates of LDLT for HCC were equal to LDLT for benign liver diseases? What criteria were used to screen HCC patients for LDLT in the authors’ institute? Milan criteria, University of California San Francisco criteria, or other criteria? Third, the distribution of the HCC was markedly skewed among the four groups (in Table 1 of Yoshizumi et al. (1)), and the FM group owned the highest proportion of HCC in the four groups (P<0.001). Although the HCC was not identified as a risk factor that predicted poor survival in the study, a subgroup analysis in the FM group should be performed according to the HCC to exclude the effect of HCC on survival. Moreover, the pretransplantation DM is another risk factor that predicted poor survival after LDLT. Similarly, the distribution of the pretransplantation DM was markedly skewed among the four groups (in Table 1 of Yoshizumi et al. (1)). The female donor to female recipient group owned the lowest proportion of pretransplantation DM (0%), whereas the FM group owned a significantly higher proportion of pretransplantation DM (20.33%) (P=0.001). In contrast, the FM group showed significantly worse patient survival rates compared with the female donor to female recipient group (P<0.01). In order to exclude the effect of pretransplantation DM on survival in the FM group, a subgroup analysis should be performed according to the pretransplantation DM. The authors can perform a subgroup analysis in the FM group according to the graft weight-standard liver weight ratio. Why did the authors not perform a subgroup analysis in the FM group according to the pretransplantation DM?