岡田 憲樹

BACKGROUND: Acute rejection remains a major complication following liver transplantation, yet reliable noninvasive biomarkers for its early prediction and diagnosis remain unidentified. This exploratory study characterized bile and serum metabolites associated with acute rejection in living donor liver transplantation using comprehensive metabolomic profiling combined with machine learning. METHODS: Non-targeted metabolomics were performed on bile samples collected on post-operative day (POD) 1 (n = 38) and serum on POD 14 (n = 45) from liver transplant recipients. Partial least squares discriminant analysis-based variable selection was followed by logistic regression and least absolute shrinkage and selection operator models, which were evaluated via cross-validation in the discovery cohort to explore potential biomarkers for acute rejection. RESULTS: A three-variable, bile-based model for predicting acute rejection achieved a mean cross-validated AUC of 0.872 (95% confidence interval: 0.814-0.930). Glycohyocholic acid and sulfolithocholylglycine were the main contributors. A nine-variable serum model for the Rejection Activity Index, including the change in γ-glutamyl transferase, showed a mean cross-validated R2 of 0.728 (95% confidence interval: 0.609-0.846), with methionine, creatine, and oxidized fatty acids contributing prominently. CONCLUSIONS: These findings suggest that metabolomic profiling combined with machine learning may provide candidate biomarkers for acute rejection after liver transplantation. However, given the exploratory nature of the study and the lack of external validation, the clinical utility of these metabolite signatures remains to be determined. Therefore, external validation in larger, independent cohorts will be required.

Liver transplant (LT) recipients, particularly pediatric survivors, face an elevated lifetime risk of de novo malignancies due to prolonged immunosuppressive therapy. Alpha-fetoprotein (AFP) is widely used as a biomarker for hepatocellular carcinoma (HCC) in post-LT surveillance, but elevations may also reflect extrahepatic tumors. Here, we report a rare case of a testicular tumor incidentally detected through AFP monitoring in a pediatric LT survivor. A 20-year-old male with situs inversus totalis underwent living donor LT for biliary atresia at 1 year of age. Nineteen years post-transplant, AFP was elevated to 493 ng/mL during routine surveillance, raising suspicion for de novo HCC. Imaging studies revealed no liver lesions, but physical examination identified testicular swelling. Scrotal ultrasonography demonstrated a heterogeneous mass, and orchiectomy confirmed a mixed germ cell tumor composed of seminoma, yolk sac tumor, and embryonal carcinoma. AFP normalized postoperatively, and the patient is being carefully monitored during postoperative surveillance. This case highlights both the benefits and limitations of AFP-driven surveillance: while it facilitated early detection of a curable extrahepatic tumor, reliance on AFP alone may miss AFP-negative testicular cancers. Comprehensive surveillance strategies incorporating tumor markers, structured physical examinations, and patient education are warranted, with future emphasis on standardized guidelines for pediatric LT survivors.

BACKGROUND: Living donor hepatectomy carries a risk of bleeding, and allogeneic transfusion may cause adverse effects. Autologous blood preparation is therefore considered a safer strategy. While preoperative autologous donation (PAD) is widely used, acute normovolemic hemodilution (ANH) may overcome its limitations and offer a practical alternative. However, evidence supporting ANH in donor surgery remains limited. This study compared the clinical utility of ANH and PAD in living donor hepatectomy. METHODS: We retrospectively analyzed 60 consecutive cases of living donor right hepatectomy performed between 2017 and 2025. Among them, 58 donors who received either PAD or ANH were compared using 1:2 propensity score matching. Perioperative laboratory values, surgical outcomes, any allogeneic transfusion, and postoperative complications were evaluated. RESULTS: No unexpected intraoperative adverse events or allogeneic transfusions occurred. All ANH donors received autologous reinfusion, compared with only 6.5% of PAD donors. After matching, 27 donors (18 PAD, 9 ANH) were analyzed. Whole blood viscosity was higher in the ANH group. Weight-adjusted intraoperative bleeding was lower (2.6 vs. 4.6 mL/kg, p = .024; q = 0.106) and operative time was shorter (321 vs. 390 min, p = .007; q = 0.077) in the ANH group. Postoperative complication rates were comparable. Area under the curve analysis indicated better preservation of total protein (p = .038) and prothrombin time-international normalized ratio (p = .010) across the perioperative period in the ANH group. CONCLUSIONS: ANH maintained transfusion avoidance and donor safety comparable to PAD while improving operative efficiency, supporting ANH as a safe, effective alternative in living donor right hepatectomy.

INTRODUCTION: Neonatal haemochromatosis, considered to be a gestational alloimmune liver disease (NH-GALD), is a rare but serious disease that results in fulminant hepatic failure. The recurrence rate of NH-GALD in a subsequent infant of a mother with an affected infant is 70%-90%. Recently, antenatal maternal high-dose intravenous immunoglobulin (IVIG) therapy has been reported as being effective for preventing recurrence of NH-GALD in a subsequent infant. However, no clinical trial has been conducted to date. METHODS AND ANALYSIS: This is a multicentre open-label, single-arm study of antenatal maternal high-dose IVIG therapy in pregnant women with a history of documented NH in a previous offspring. The objective of this study is to evaluate the efficacy and safety of antenatal maternal high-dose IVIG therapy in preventing or reducing the severity of alloimmune injury to the fetal liver. ETHICS AND DISSEMINATION: The clinical trial is being performed in accordance with the Declaration of Helsinki. The trial protocol was approved by the Clinical Research Review Board at four hospitals. Before enrolment, written informed consent would be obtained from eligible pregnant women. The results are expected to be published in a scientific journal. PROTOCOL VERSION: 28 October 2024, V.8.0. TRIAL REGISTRATION NUMBER: jRCT1091220353.