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Platelet concentrates (PCs) are widely used in regenerative medicine; as it is produced from freeze–thawing PC, platelet lysate (PL) has a longer shelf life. The thrombotic risk of PL therapy needs to be explored since PL and PC contain cytokines that contribute to platelet aggregation and thrombus formation. Whole blood samples of 20 healthy subjects were collected; PL was produced from PCs with expired shelf life through freeze–thawing. The direct mixing of PL with platelet-rich plasma (PRP) or whole blood was performed. In addition, rotational thromboelastometry (ROTEM) was used to investigate whether PL enhanced coagulation in vitro; the effects of fibrinogen depletion and anticoagulants were evaluated to prevent hypercoagulation. The results showed that PL induced platelet aggregation in both PRP and whole blood. In ROTEM assays, PL was shown to cause a significantly lower clotting onset time (COT) and clot formation time (CFT), and a significantly greater α angle and maximum clot firmness (MCF). Compared with the controls, which were 1:1 mixtures of normal saline and whole blood, fibrinogen depletion of PL showed no significant difference in CFT, α angle and MCF. Moreover, heparin- and rivaroxaban-added PL groups demonstrated no clot formation in ROTEM assays. Platelet lysate-induced hypercoagulability was demonstrated in vitro in the present study, which could be prevented by fibrinogen depletion or the addition of an anticoagulant. [ABSTRACT FROM AUTHOR]

ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) can be performed successfully. However, anti-ABO isoagglutinin rebound may cause antibody-mediated rejection (AMR) and graft loss. The risk threshold of isoagglutinin rebound is still not defined. 76 ABO-I LDLT recipients were divided into group A (n = 56) with low isoagglutinin titers (<1:256), and group B (n = 20) with high isoagglutinin titers (≥1:256), at initial assessment for liver transplantation. The last 12 patients in group B received a modified desensitization regimen by adding bortezomib to deplete plasma cells. Six (10.7%) patients in group A and 10 (50.0%) patients in group B had postoperative isoagglutinin rebound (p < 0.001). Three patients (5.54%) in group A and two patients (10%) in group B developed clinical AMR (p = 0.602). The cutoff value of postoperative isoagglutinin rebound to cause clinical AMR was ≥1:1024. Among the 12 patients in group B with bortezomib administration, isoagglutinin rebounded up to 1:128 only, and no clinical AMR occurred. In conclusion, the patients with high isoagglutinin titers had a higher rate of postoperative isoagglutinin rebound. Isoagglutinin rebound ≥1:1024 is risky for developing clinical AMR. Adding bortezomib into the desensitization regimen may mitigate isoagglutinin rebound, and avoid clinical AMR. [ABSTRACT FROM AUTHOR]

Simple Summary: Liver transplantation (LT) is an optimal treatment option for hepatocellular carcinoma (HCC) associated with cirrhosis. Additionally, the transplantation community is eager to expand the criteria for transplantation to accommodate more patients with HCC. Despite numerous efforts to broaden LT eligibility, HCC with portal vein tumor thrombosis (PVTT) remains a contraindication due to the associated risk of poor prognosis after transplantation. However, there have been arguments addressing the dilemma of LT in cases of HCC with PVTT. This study aimed to analyze the outcomes of LT in patients with HCC and portal vein thrombosis, specifically evaluating the impact of PVTT on long-term outcomes. The results indicate that the presence of residual viable tumor within the portal vein thrombus may lead to poor outcomes following LT. Therefore, patients with HCC and PVTT could still be considered for LT after appropriate downstaging treatment. However, caution should be exercised regarding the potential for residual viable PVTT, which may result in unsatisfactory outcomes after LT. Background: Liver transplantation (LT) is a promising treatment option for patients with hepatocellular carcinoma (HCC) comorbid with cirrhosis. However, HCC with portal vein tumor thrombosis (PVTT) remains an absolute contraindication for LT. This study aimed to analyze the outcomes of LT in patients with HCC plus portal vein thrombosis and further evaluate the impact of PVTT on the long-term outcomes of patients. Methods: Among the 501 patients who underwent LT for HCC between January 2000 and March 2023, 29 (5.8%) patients with HCC who had portal vein thrombosis were further analyzed. Of these 29 patients with portal vein thrombosis, 12 (41.4%) were preoperatively diagnosed with PVTT and underwent LT after receiving downstaging therapy. The remaining 17 (58.6%) patients were PVTT-free prior to LT. Results: Overall, the recurrence-free survival rates at 1, 3, and 5 years were 96.3%, 74.2%, and 74.2%, respectively, while the 1-, 3-, and 5-year overall survival rates were 82.4%, 74.2%, and 70.1%, respectively. However, patients with viable PVTT had significantly worse outcomes than those without viable PVTT (p = 0.030). The 5-year recurrence-free and overall survival rates for patients with viable PVTT were 57.5% and 57.0%, respectively. Conclusions: LT may still be a promising option for patients with HCC and PVTT after appropriate downstaging. However, caution should be adopted, as remnant viable PVTT might lead to unsatisfactory outcomes after transplantation. [ABSTRACT FROM AUTHOR]

Background: Diagnostic tests for early allograft dysfunction (EAD) after living donor liver transplantation (LDLT) vary widely. We aimed to evaluate the predictive value of rotational thromboelastometry (ROTEM)-derived parameters in EAD. Materials and Methods: A total of 121 patients were reviewed. The definition of EAD proposed by Olthoff et al. included the presence of any of the following at postoperative day 7: bilirubin level ≥ 10 mg/dL, INR ≥ 1.6, or serum AST or ALT levels > 2000 IU/L. All patients underwent ROTEM assay, which consisted of an extrinsically activated thromboelastometric test (EXTEM) before and 24 h after LDLT. Results: The 1-year/2-year OS were 68.%8/64.5% and 94.4%/90.8% for the EAD and non-EAD groups, respectively (p = 0.001). Two independent risks were identified for EAD, the postoperative clotting time (CT, p = 0.026) and time to maximum clot firmness (maximum clot firmness (MCF)-t, p = 0.009) on the EXTEM. CT yielded a specificity of 82.0% and negative predictive value of 83.0%, and MCF-t displayed a specificity of 76.4% and negative predictive value of 81.9% in diagnosing EAD. The use of the 24 h post-LDLT ROTEM increased the effectiveness of predicting overall survival (OS) compared to using the Olthoff's EAD criteria alone (p < 0.001). Conclusion: We conclude that CT and MCF on EXTEM were independent predictors of EAD. The 24 h post-LDLT ROTEM can be used with conventional laboratory tests to diagnose EAD. It increases the effectiveness of predicting OS. [ABSTRACT FROM AUTHOR]

Dexmedetomidine, an α2-adrenergic receptor agonist, is used as an anti-anxiety medication. It exerts a cholinergic effect, thereby reducing the release of tumor necrosis factor alpha (TNF-α). We hypothesized that the use of dexmedetomidine as a sedative agent in transplantation would also protect allografts. We examined our patients who underwent living donor liver transplantation. Subsequently, we generated a series of mouse models to investigate the effect of dexmedetomidine on sedation-based tolerance post transplantation. A total of 49 liver recipients were enrolled in this study, of which 23 (47%) were administered dexmedetomidine through 24 h infusion on postoperative day 1. A trend toward the improvement of hepatocyte injury along with better liver function was observed in the dexmedetomidine-treated group during the first postoperative week. In animal models, dexmedetomidine inhibited the proliferation of CD4+ and CD8+ T cells and TNF-α production in a dose-dependent manner. We used dexmedetomidine to treat skin-transplanted mice and observed a significantly prolonged graft survival in mice that were administered a higher dose of dexmedetomidine. Our results revealed that dexmedetomidine exerts a dual effect of sedation and immunosuppression. This light-sedation approach will not only make patients calmer in the intensive care unit but also protect allografts from injury. [ABSTRACT FROM AUTHOR]

Background: We aimed to develop a novel scoring system for risk stratification specific to living donor liver transplantation (LDLT) recipients, to improve the accuracy of predicting short-term outcomes. Methods: The sequential organ failure assessment (SOFA) score at postoperative day 7 was collected and simplified by dichotomization, and these categories and other clinical factors were subjected to univariate and multivariate logistic regression analyses to select independent risks in constructing a "graft-to-recipient weight ratio (GRWR)-SOFA" scoring system. Results: We enrolled 519 patients who underwent LDLT. The GRWR-SOFA score comprises a sum of six factors: cardiovascular (mean arterial pressure < 70 mmHg, scored 3), coagulation (serum platelet < 50 × 103/μL, scored 2), renal (creatinine > 1.2 mg/dL, scored 2), liver (serum total bilirubin > 5.9 mg/dL, scored 5), neurological (Glasgow coma scale < 15, scored 2), and GRWR < 0.8, scored 2. The GRWR-SOFA contained four classes: The early mortality rate at 3 months and 1 year after LDLT was 1.3% and 6.9% for class I (scores of 0–4), 9.1% and 16.7% for class II (scores of 5–8), 25.5% and 34% for class III (scores of 9–10), and 61.3% and 67.7% for class IV (scores ≥ 11), respectively. The area under the receiver operating characteristic curve of GRWR-SOFA in the 3-month mortality prediction was 0.881 (95% confidence interval (CI): 0.818–0.944). Conclusions: The GRWR-SOFA model demonstrates superior discriminatory power for predicting short-term mortality. It enables clinicians to identify the right level of care for distinct subgroups of patients receiving LDLT. [ABSTRACT FROM AUTHOR]

Liver transplant recipients are immunocompromised and have low immunogenicity to produce antibodies in anti-COVID-19 vaccination. Whether immunosuppressant adjustment could facilitate anti-COVID-19 antibody production in anti-COVID-19 mRNA vaccination is undetermined. Our patients were informed to temporarily suspend mycophenolate mofetil (MMF) or everolimus (EVR) for 2 weeks during both the 1st and 2nd doses of Moderna mRNA-1273 vaccine. A total of 183 recipients receiving two doses of Moderna mRNA-1273 vaccine were enrolled and grouped into tacrolimus monotherapy (MT, n = 41), and dual therapy with non-adjustment (NA, n = 23), single suspension (SS, n = 19) and double suspension (DS, n = 100) of MMF/EVR in two-dose mRNA vaccination. A total of 155 (84.7%) patients had a humoral response to vaccines in this study. The humoral response rates were 60.9%, 89.5%, 91.0% and 80.5% in NA, SS, DS, and MT group patients, respectively (p = 0.003). Multivariate analysis showed that favorable factors for humoral response were temporary suspension of MMF/EVR and monotherapy, and unfavorable factors were deceased donor liver transplantation, WBC count < 4000/uL, lymphocyte < 20% and tacrolimus trough level ≥ 6.8 ng/mL. In conclusion, temporary two-week suspension of anti-proliferation immunosuppressants could create a window to facilitate antibody production during anti-COVID-19 mRNA vaccination. This concept may be applied to other vaccinations in liver transplant recipients. [ABSTRACT FROM AUTHOR]

Simple Summary: Currently, two established staged hepatectomy techniques are used for curative resection of advanced colorectal liver metastasis (CRLM) as well as preventing inadequate future remnant liver (FRL). However, the selection of staged hepatectomy between the conventional two-stage hepatectomy (cTSH) and the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) remains under debate. Therefore, the present study proposed a selection criterion based on tumor burden related to the size and number of metastases within the FRL for decision making when utilizing staged hepatectomy for advanced CRLM. Accordingly, metastatic tumors within the FRL should not exceed three nodules and none of the nodules should measure larger than 3 cm for ALPPS. By contrast, cTSH would be considered in patients whose tumor burdens within the FRL beyond the aforementioned criteria. The individualized selection criteria appear to be promising and can be used to select a more effective staged hepatectomy approach for patients with advanced CRLM. Staged hepatectomy is a promising strategy for curative resection of advanced colorectal liver metastasis (CRLM) to prevent inadequate future remnant liver (FRL). However, the selection criteria for conventional two-stage hepatectomy (cTSH) and associating liver partitioning and portal vein ligation for staged hepatectomy (ALPPS) remain unclear. This study aimed to propose a selection criterion for determining the optimal staged hepatectomy for patients with advanced CRLM. A selection criterion based on the degree of metastatic tumors within the FRL was established to determine staged hepatectomy approaches. Generally, ALPPS is recommended for patients with ≤3 metastatic nodules and whose nodules do not measure >3 cm in the FRL. cTSH is performed for patients whose tumor burden in FRL beyond the selection criteria. Data of 37 patients who underwent staged hepatectomy and curative intent of CRLM were analyzed. The clinical characteristics and outcomes of the two approaches were compared. Overall, cTSH and ALPPS were performed for 27 (73.0%) and 10 (27.0%) patients, respectively. Of those, 20 patients in the cTSH group and all patients in the ALPPS group had completed staged hepatectomy. The 1-, 3-, and 5-year survival rates were 91.6%, 62.4%, and 45.4% for all patients, respectively. The outcomes of patients who had successfully completed the staged hepatectomy were significantly better than those of other patients who failed to achieve staged hepatectomy. However, no significant difference was observed in the overall survival of patients who underwent staged hepatectomy between the two groups, but those in the ALPPS group had 100% survival at the end of this study. The individualized selection criteria based on tumor burden in the FRL that could balance the operative risk and oncologic outcome appear to be a promising strategy for achieving complete staged hepatectomy in patients with advanced CRLM. [ABSTRACT FROM AUTHOR]

Background: Patients with hepatocellular carcinoma (HCC) tend to be referred for liver transplantation (LT) at an early stage of cirrhosis, with lower pre-LT Model of End-Stage Liver Disease (MELD) scores. We investigated the impact of high MELD scores on post-LT outcomes in patients with HCC and validated the prognostic significance of the neutrophil-to-lymphocyte ratio (NLR). Patients and Method: This retrospective single-center cohort study enrolled 230 patients with HCC who underwent LDLT from 2004–2019 in our institute. We defined a high MELD score as ≥20. Results: The MELD < 20 and MELD ≥ 20 groups comprised 205 and 25 cases, respectively. Although there was no significant difference in disease-free survival between the two groups (p = 0.629), the incidence of septic shock (p = 0.019) was significantly higher in the high MELD group. The one-, three-, and five-year overall survival rates were not significantly different between the two groups (p = 0.056). In univariate analysis, a high pre-LT NLR was associated with poorer survival in the high MELD group (p = 0.029, hazard ratio [HR]: 1.07, 90% confidence interval [CI]: 1.02–1.13). NLR cut-off values of ≥10.7 and <10.7 were predictive of mortality, with an AUC of 0.705 (90% CI: 0.532–0.879). The one-, three-, and five-year post-LT survival rates were significantly higher among the recipients with an NLR < 10.7 than those with an NLR ≥ 10.7 (p = 0.005). Conclusions: Pre-LT MELD score ≥ 20 was associated with a higher risk of developing post-LT septic shock and mortality. The pre-LT serum NLR is a useful predictive factor for clinical outcomes in patients with HCC with high MELD scores. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) occurring at the left lateral segment (LLS) is relatively susceptible to treatment with curative intent in terms of tumor location. However, outcomes might vary depending on the selection of treatment modalities. This study aimed to analyze patients who had undergone curative treatment for early HCC at LLS. Methods: A retrospective analysis of 179 patients who underwent curative treatment for early HCC at LLS was performed. Patients were grouped based on treatment modalities, including radiofrequency ablation (RFA) and liver resection (LR). The long-term outcomes of the two groups were compared. Additionally, the impact of the LR approach on patient outcomes was analyzed. Results: Among these patients, 60 received RFA and 119 underwent LR as primary treatment with curative intent. During follow-up, a significantly higher incidence of HCC recurrence was observed in the RFA group (37/60, 61.7%) than in the LR group (45/119, 37.8%) (p = 0.0025). The median time of HCC recurrence was 10.8 (range: 1.1–60.9 months) and 17.6 (range: 2.4–94.8 months) months in the RFA and LR groups, respectively. In addition, multivariate analysis showed that liver cirrhosis, multiple tumors, and RFA treatment were significant risk factors for HCC recurrence. The 1-, 2-, and 5-year overall survival rates in the RFA and LR groups were 96.4%, 92.2%, and 71.5% versus 97.3%, 93.6%, and 87.7%, respectively. (p = 0.047). Moreover, outcomes related to LR were comparable between laparoscopic and conventional open methods. The 1-, 2-, and 5-year recurrence free survival rates in the laparoscopic (n = 37) and conventional open (n = 82) LR groups were 94.1%, 82.0%, and 66.9% versus 86.1%, 74.6%, and 53.1%, respectively. (p = 0.506) Conclusion: Early HCC at LLS had satisfactory outcomes after curative treatment, in which LR seems to have a superior outcome, as compared to RFA treatment. Moreover, laparoscopic LR could be considered a preferential option in the era of minimally invasive surgery. [ABSTRACT FROM AUTHOR]

Simple Summary: Microvascular invasion (MVI) is the most consistently reported risk factor for recurrence after curative treatment in hepatocellular carcinoma (HCC), but the preoperative prediction of MVI is still challenging. We retrospectively collected 1153 patients who underwent liver resection for HCC, and our multivariate analysis revealed preoperative total tumor volume (TTV) and alpha-fetoprotein (AFP) to be independent risk factors for MVI. We used both factors to build a risk score model that is easy to calculate and objective, with minimal user bias. The preoperative prediction of MVI can guide the treatment plan of HCC, including surgical planning, criteria for transplantation, and adjuvant or neoadjuvant therapy. Our risk score model is easily and widely applicable with moderate performance, which optimizes clinical practice and helps study design in the future. Microvascular invasion (MVI) is a significant risk factor for the recurrence of hepatocellular carcinoma, but it is a histological feature that needs to be confirmed after hepatectomy or liver transplantation. The preoperative prediction of MVI can optimize the treatment plan of HCC, but an easy and widely applicable model is still lacking. The aim of our study was to predict the risk of MVI using objective preoperative factors. We retrospectively collected 1153 patients who underwent liver resection for HCC, and MVI was found to be associated with significantly poor disease-free survival. The patients were randomly split in a 3:1 ratio into training (n = 864) and validation (n = 289) datasets. The multivariate analysis of the training dataset found preoperative total tumor volume (TTV) and alpha-fetoprotein (AFP) to be independent risk factors for MVI. We built a risk score model with cutoff points of TTV at 30, 60, and 300 cm3 and AFP at 160 and 2000 ng/mL, and the model stratified the risk of MVI into low risk (14.1%), intermediate risk (36.4%), and high risk (60.5%). The validation of the risk score model with the validation dataset showed moderate performance (the concordance statistic: 0.731). The model comprised simple and objective preoperative factors with good applicability, which can help to guide treatment plans for HCC and future study design. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma is the most common liver malignancy. In the population with an advanced stage of the disease, outcomes could be disappointed by treating with molecular targeting agents because of low treatment response rates. It has gained improving effects of immune checkpoint inhibitor as an emerging treatment for advanced HCC (Hepatocellular carcinoma). However, this novel treatment regimen is quite expensive; to select suitable patients prior to treatment is crucial in daily practice. Here, we intend to present the effect of immunotherapy in treating advanced hepatocellular carcinoma in the real world and to assess potential factors predicting treatment responses for patient selection. Immune checkpoint inhibitors (ICI) have been applied to treat advanced stage hepatocellular carcinoma (HCC) and obtain promising effects. However, tumor response to treatment was unpredictable. A predicting biomarker of objective response or disease-control is an unmet need for patient selection. In this study, 45 advanced HCC patients who failed to sorafenib treatment and received nivolumab, 3 mg/kg bi-weekly, were included. Tumor responses to nivolumab treatment were assessed by the modified response evaluation criteria in solid tumors (mRECIST) criteria. Tumor responses were correlated to clinical characteristics to find out response predictors. In this small series, the prevalence of extrahepatic nodal metastasis, distant metastasis, and portal vein thrombus among the patients were 22.2% (n = 10), 48.9% (n = 22), and 42.2% (n = 19), respectively. The pre-treatment tumor size was 7.2 ± 4.2 cm in maximal diameter, and the calculated total tumor volume was 619.0 ± 831.1 cm3. Among 45 patients, 3 patients had partial response (PR), 11 had stable disease (SD), and the other 31 had progression of disease. By correlating clinical data to the patients with PR and SD, serum neutrophil-to-lymphocyte ratio (NLR) (hazard ratio (HR) = 2.04) and patient-generated subjective global assessment (PG-SGA) score (HR = 2.30) were the independent factors in multivariate analysis. By receiver operating characteristic curve analysis, pre-treatment NLR ≤ 2.5 and PG-SGA score < 4 were the cutoff points to predict tumor response to ICI treatment. In conclusion, biomarkers to predict tumor response for HCC are still lacking in this costly ICI therapy. In this study, NLR ≤ 2.5 and PG-SGA score < 4 indicated disease-control, and can be applied as biomarkers to select the right patients to receive this costly therapy. [ABSTRACT FROM AUTHOR]

Portal vein thrombus (PVT) is a challenge in liver transplantation. How PVT develops in cirrhotic patients who already have coagulopathy is unclear. This study aimed to investigate possible contributing factors to PVT in cirrhotic patients. A total of 349 cirrhotic patients who waited liver transplantation were included in this study and 48 of them had PVT. For all the patients, the mean age was 53.5 ± 9.0 year old, and 75.9% of the patients were male. There were 233 (66.8%) patients who had either hepatitis B or C. The mean Model For End-Stage Liver Disease (MELD) score was 16.4 ± 7.5. Eighteen of 48 patients with PVT and 145 of 301 patients without PVT received liver transplantation. Multivariate analysis showed that low protein S level (hazard ratio = 2.46, p = 0.017) was the only independent risk factor for PVT development. Protein S deficiency also demonstrated prognostic value on short-term survival, not only for cirrhotic patients awaiting liver transplantation (69.9% versus 84.1% at 1 year survival, p = 0.012), but also for the patients having liver transplantation (70.4% versus 84.8% at 1 year survival, p = 0.047). In conclusion, protein S level was an independent risk factor for PVT development in decompensated cirrhotic patients, and protein S deficiency was also a prognostic factor for the patients waiting for liver transplantation. [ABSTRACT FROM AUTHOR]

Background: Organ demand for liver transplantation (LT) is constantly increasing. Split liver transplantation (SPLT) is an ideal option for increasing the number of available liver grafts for transplantation and ameliorating organ shortage to a certain degree. However, SPLT for two adult recipients is still not broadly applied. Methods: We retrospectively analyzed the outcomes of SPLT for adult recipients at a single center. All donor, recipient, and transplantation factors were thoroughly investigated to clarify factors affecting patient outcomes after LT. Results: One hundred consecutive adult SPLTs were performed during the study period. Early mortality and 1-year mortality occurred in 21 and 31 recipients, respectively. On multivariate analysis, graft weight (p = 0.036, odds ratio = 0.99, 95% confidence interval = 0.98–0.99) was the independent risk factor associated with early mortality; however, no factor was significantly related to 1-year mortality. On receiver operating characteristic curve analysis, a graft weight of 580 g was identified the cutoff for stratifying outcomes. Recipients transplanted with a graft weighing ≥580 g had significantly better outcome as compared with other recipients (p = 0.001). Moreover, SPLT remarkably provided a better survival benefit for recipients than those on the LT wait-list (p < 0.0001). Conclusions: Given the considerable incidence of wait-list mortality, SPLT for two adult recipients should be encouraged whenever possible to increase the donor pool and benefit patients awaiting LT. Nonetheless, caution should be taken with a smaller graft weight owing to the risk of early graft loss. [ABSTRACT FROM AUTHOR]

Liver transplantation can be performed with deceased or living donor allografts. Deceased liver grafts are donated from brain- or circulation-death patients, and they have usually suffered from a certain degree of damage. Post-transplant graft function and patient survival are closely related to liver allograft recovery. How to define the damage of liver grafts is unclear. A total of 47 liver donors, 23 deceased and 24 living, were enrolled in this study. All deceased donors had suffered from severe brain damage, and six of them had experienced cardio-pulmonary-cerebral resuscitation (CPR). The exploration of liver graft metabolomics was conducted by liquid chromatography coupled with mass spectrometry. Compared with living donor grafts, the deceased liver grafts expressed higher levels of various diacylglycerol, lysophosphatidylcholine, lysophosphatidylethanolamine, oleoylcarnitine and linoleylcarnitine; and lower levels of cardiolipin and phosphatidylcholine. The liver grafts from the donors with CPR had higher levels of cardiolipin, phosphatidic acid, phosphatidylcholine, phatidylethanolamine and amiodarone than the donors without CPR. When focusing on amino acids, the deceased livers had higher levels of histidine, taurine and tryptophan than the living donor livers. In conclusion, the deceased donors had suffered from cardio-circulation instability, and their lipid metabolites were increased. The elevation of lipid metabolites can be employed as an indicator of liver graft suffering.

Human cytomegalovirus (CMV) infection has been reported to compromise liver transplantation (LT) outcomes. Recent studies have shown that CMV has a beneficial oncolytic ability. The aim of this study was to investigate the impact of CMV on tumor recurrence in patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT). This retrospective study enrolled 280 HCC patients with LT at our institute between January 2005 and January 2016. Their relevant demographic characteristics, pre- and post-LT conditions, and explant histology were collected. A CMV pp65 antigenemia assay was performed weekly following LT to identify CMV infection. A total of 121 patients (43.2%) were CMV antigenemia-positive and 159 patients (56.8%) were negative. A significantly superior five-year recurrence-free survival was observed among CMV antigenemia-positive patients compared with the CMV-negative group (89.2% vs. 79.9%, p = 0.049). There was no significant difference in overall survival between the positive and negative CMV antigenemia groups (70.2% vs. 75.3%, p = 0.255). The major cause of death was HCC recurrence in CMV antigenemia-negative patients (51.3%), whereas more CMV antigenemia-positive patients died due to other bacterial or fungal infections (58.3%). In the multivariate analysis, the independent risk factors for tumor recurrence included positive CMV antigenemia ( p = 0.042; odds ratio (OR) = 0.44; 95% confidence interval (CI) = 0.20-0.97), microscopic vascular invasion ( p = 0.001; OR = 3.86; 95% confidence interval (CI) = 1.78-8.36), and tumor status beyond the Milan criteria ( p = 0.001; OR = 3.69; 95% CI = 1.77-7.71). In conclusion, in addition to the well-known Milan criteria, human CMV is associated with a lower HCC recurrence rate after LT. However, this tumor suppressive property does not lead to prolonged overall survival, especially in severely immunocompromised patients who are vulnerable to other infections.