Japanese living donor liver transplantation criteria for hepatocellular carcinoma: nationwide cohort study.

BACKGROUND: Validating the expanded criteria for living donor liver transplantation for hepatocellular carcinoma using national data is highly significant. The aim of this study was to evaluate the validity of the new Japanese criteria for living donor liver transplantation for hepatocellular carcinoma patients and identify factors associated with a poor prognosis using the Japanese national data set. METHODS: The study population comprised patients who underwent living donor liver transplantation for hepatocellular carcinoma at 37 centres in Japan between 2010 and 2018. In a nationwide survey, the overall survival and recurrence-free survival rates were evaluated based on the new Japanese criteria for applying the 5-5-500 rule when extending the indication beyond the Milan criteria. Prognostic factors within the Japanese criteria were determined using the Cox proportional hazards model. RESULTS: Patients within (485 patients) and beyond (31 patients) the Japanese criteria exhibited 5-year overall survival rates of 81% and 58% and 5-year recurrence-free survival rates of 77% and 48% respectively. Patients who met the Milan criteria, but not the 5-5-500 rule, had poorer outcomes. Multivariate analysis for 474 patients identified a neutrophil-to-lymphocyte ratio greater than or equal to 5 and a history of hepatectomy as independent risk factors. CONCLUSION: This nationwide survey confirms the validity of the Japanese criteria. The poor prognostic factors within the Japanese criteria include a neutrophil-to-lymphocyte ratio greater than or equal to 5 and previous hepatectomy.

Improved survival of pediatric deceased donor liver transplantation recipients after introduction of the pediatric prioritization system: Analysis of data from a Japanese national survey.

BACKGROUND: In Japan, there has never been a national analysis of pediatric deceased donor liver transplantation (pDDLT) based on donor and recipient factors. We constructed a Japanese nationwide database and assessed outcomes of pDDLT focusing on the pediatric prioritization system introduced in 2018. METHODS: We collected data on pDDLTs (<18 years) performed between 1999 and 2021 from the Japan Organ Transplant Network and Japanese Liver Transplantation Society, identified risk factors for graft survival and compared the characteristics and graft survival in pDDLTs conducted before and after the introduction of the pediatric prioritization system. RESULTS: Overall, 112 cases of pDDLT were included, with a 1-year graft survival rate of 86.6%. Four poor prognostic factors were identified: recipient intensive care unit stay, model for end-stage liver disease/pediatric end-stage liver disease score, donor cause of death, and donor total bilirubin. After the introduction of the system, allografts from pediatric donors were more reliably allocated to pediatric recipients and the annual number of pDDLTs increased. The 1-year graft survival rate improved significantly as did pDDLT conditions indicated by the risk factors. CONCLUSIONS: Under the revised allocation system, opportunities for pDDLT increased, resulting in favorable recipient and donor conditions and improved survival.

Interleukin-33 and liver natural killer cells: A novel perspective on antitumor activity in liver fibrosis.

AIM: Liver fibrosis, heralding the potential progression to cirrhosis and hepatocellular carcinoma (HCC), compromises patient survival and augments post-hepatectomy recurrence. This study examined the detrimental effects of liver fibrosis on the antitumor functions of liver natural killer (NK) cells and the interleukin-33 (IL-33) signaling pathway. METHODS: Our investigation, anchored in both human physiologies using living and deceased donor livers and the carbon tetrachloride (CCl4)-induced mouse fibrosis model, aimed to show a troubling interface between liver fibrosis and weakened hepatic immunity. RESULTS: The Fibrosis-4 (FIB-4) index emerged as a salient, non-invasive prognostic marker, and its elevation correlated with reduced survival and heightened recurrence after HCC surgery even after propensity matching (n = 385). We established a strong correlation between liver fibrosis and liver NK cell dysfunction by developing a method for extracting liver NK cells from the liver graft perfusate. Furthermore, liver fibrosis ostensibly disrupted chemokines and promoted IL-33 expression, impeding liver NK cell antitumor activities, as evidenced in mouse models. Intriguingly, our results implicated IL-33 in diminishing the antitumor responses of NK cells. This interrelation, consistent across both mouse and human studies, coincides with clinical data suggesting that liver fibrosis predisposes patients to an increased risk of HCC recurrence. CONCLUSION: Our study revealed a critical relationship between liver fibrosis and compromised tumor immunity, emphasizing the potential interference of IL-33 with NK cell function. These insights advocate for advanced immunostimulatory therapies targeting cytokines, such as IL-33, aiming to bolster the hepatic immune response against HCC in the context of liver fibrosis.

Delayed peak antibody titers after the second dose of SARS-CoV-2 vaccine in solid organ transplant recipients: Prospective cohort study.

Poor post-vaccination production of antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a concern among solid organ transplant (SOT) recipients. Furthermore, the timing and kinetics of antibody titers after the second vaccine dose are unknown. We conducted a multicenter prospective observational study that included 614 SOT recipients: 460 kidney, 53 heart, 50 liver, 20 lung, and 31 simultaneous pancreas-kidney (SPK). The participants received two doses of the mRNA vaccine (Pfizer BNT162b2 or Moderna mRNA-1273), as indicated. Serum samples were collected before the first and second vaccinations and at 1, 3, and 6 months after the second vaccine dose, which were then assessed for SARS-CoV-2 antibodies. The overall seropositivity rate was 43% at 1 month after administration of the second vaccine dose; it gradually increased to 68% at 3 months after second dose administration and to 70% at 6 months. In addition, recipient of kidney, lung or SPK transplants had lower antibody titers at the 3- and 6-month time points than did the other recipients. SOT recipients acquired SARS-CoV-2 S-IgG antibodies slowly, and the peak titer differed significantly from that of the general population.

Exploratory study on the impact of intraesophageal pressure on quality of life in patients following total gastrectomy: a retrospective cohort study.

BACKGROUND: The usefulness of high-resolution impedance manometry (HRIM) in patients who underwent total gastrectomy with Roux-en-Y (R-Y) anastomosis has never been well validated. This study aimed to investigate whether intraesophageal pressure affects quality of life in patients who underwent total gastrectomy with R-Y anastomosis. METHODS: The participants comprised 12 patients who underwent total gastrectomy for gastric cancer between October 2014 and July 2022 and underwent a postsurgical HRIM examination. The association between the HRIM data and Postgastrectomy Syndrome Assessment Scale-37 (PGSAS-37) questionnaires was analyzed. RESULTS: Esophageal body motility was normal in almost all patients. The anastomosis shape (circular stapler and overlap method with linear stapler) did not influence intraesophageal pressure. The integrated relaxation pressure and lower esophageal sphincter (LES) residual pressure during swallowing-induced relaxation were involved in "diarrhea subscale" scores (p = 0.0244 and p = 0.0244, respectively). The average maximum intrabolus pressure was not involved in postgastrectomy symptom. The contractile front velocity correlated with the "indigestion subscale," "diarrhea subscale," and "constipation subscale" (p = 0.0408, p = 0.0143, and p = 0.0060, respectively). The distal latency, i.e., the time from upper esophageal sphincter relaxation to contractile deceleration, was also associated with the "abdominal pain subscale" (p = 0.0399). LES pressure and esophageal body motility affected patients' quality of life after total gastrectomy. CONCLUSIONS: HRIM for the evaluation of intraesophageal pressure is useful for the functional assessment of esophagojejunostomy with the R-Y reconstruction after total gastrectomy.

Clinicopathological features of hepatoid adenocarcinoma of the stomach: A multicenter retrospective study.

BACKGROUND: Hepatoid adenocarcinoma of the stomach (HAS) is a rare and aggressive subtype of gastric cancer (GC), accounting for less than 1% of all cases. It is characterized by frequent liver metastasis recurrence and a poorer prognosis than conventional GC. However, established treatment guidelines for HAS are currently not available.In this report, we present the results of a clinicopathological study of 19 patients diagnosed with HAS, including seven patients with liver metastasis, conducted by the Hiroshima Surgical Study Group of Clinical Oncology (HiSCO) between 2016 and 2018. AIMS: The aim of the study was to retrospectively observe the outcomes of HAS with gastrectomy and hepatectomy for liver metastasis and determine relevant prognostic factor. We also examined the criteria and outcomes of hepatectomy for liver metastasis and aimed to suggest the optimal treatment for HAS, including chemotherapy. METHODS AND RESULTS: A total of 2147 patients underwent gastrectomy for GC at HiSCO-affiliated institutions during the study period; 19 patients, all male with a mean age of 70.9 years, were diagnosed with HAS by hematoxylin-eosin and immunohistochemical staining. Patients underwent gastrectomy at varying pathological stages: six at Stage I, three at Stage II, seven at Stage III, and three at Stage IV. Ten patients received postoperative chemotherapy and the 5-year survival rate was 67.7% after gastrectomy. Among the seven patients with pre or postoperative liver metastasis, five patients underwent hepatectomy. Although one patient had recurrence, the 3-year survival rate was 100% after hepatectomy. CONCLUSION: Contrary to previous reports suggesting a 3-year survival rate of approximmately 30% for HAS, our findings indicate that the prognosis for HAS may not be as poor as reported previously. This study contributes valuable insights into the management and potential treatment strategies for HAS.

Serum Calcification Propensity T50 Is Associated with Soluble Thrombomodulin in Patients on Hemodialysis.

Background/Objectives: Levels of circulating soluble thrombomodulin (sTM), an anticoagulant factor, are associated with the severity and progression of arteriosclerotic diseases. However, the role of elevated sTM levels remains to be clarified in patients on dialysis. As the calcification propensity time T50 is a novel marker of arterial calcification, we aimed to determine the association between sTM and T50 in patients on hemodialysis (HD). Methods: This cross-sectional study included 49 adult patients on maintenance HD. Correlation analysis was performed to test the association between T50 and patient characteristics. Linear regression was used to evaluate the association between T50 and sTM. Results: Partial correlation analysis showed a strong association between T50 and glycated albumin, phosphorous, and sTM levels (partial correlation coefficient: r [partial] = -0.359, p = 0.023; r [partial] = -0.579, p < 0.001; and r [partial] = 0.346, p = 0.029, respectively). Multivariate linear regression analysis revealed that only sTM level was significantly and positively associated with T50 (ß = 0.288; t = 2.27; p = 0.029; 95% confidence interval, 0.082-1.403). Conclusions: sTM is independently and positively associated with the propensity time for calcification, suggesting that sTM could be a good marker of arterial calcification progression in patients on HD.

Bowel pseudo-obstruction caused by goblet cell adenocarcinoma of the appendix: A case report.

INTRODUCTION: Goblet cell adenocarcinoma of the appendix is a rare diagnosis with features of both adenocarcinomas and carcinoid tumors. Commonly presenting with chronic abdominal pain, appendicitis, or abdominal distention, it can also be incidentally discovered during appendectomies. CASE PRESENTATION: A 50-year-old man with right lower abdominal pain was admitted to our hospital, which is a critical care center. A computed tomography(CT) scan showed ileal narrowing, but endoscopy found no strictures. He was admitted with suspected bowel obstruction and improved with an ileal tube. Laparoscopic surgery revealed a tumor of the appendix. Histologically, he was diagnosed goblet cell adenocarcinoma, suggesting tumor infiltration of nerve fibers impairing peristalsis. DISCUSSION: Goblet cell adenocarcinoma of the appendix has unique histology and a poor prognosis. Treatment typically involves surgery and chemotherapy. This case highlights challenges in preoperative diagnosis, with the tumor causing bowel pseudo-obstruction by invading the intestinal wall and nerve plexus. Extensive infiltration of Auerbach's plexus was observed, consistent with the length of intestinal stenosis. CONCLUSION: This case describes goblet cell adenocarcinoma of the appendix leading to bowel pseudo-obstruction due to ileal end stenosis. It emphasizes the importance of considering this diagnosis in cases of bowel obstruction without an obvious mass.

Right-sided versus left-sided colorectal cancer in elderly patients: a sub-analysis of a large multicenter case-control study in Japan.

PURPOSE: This study investigated the impact of sidedness of colorectal cancer (CRC) in elderly patients on the prognosis. METHODS: In a sub-analysis of a multicenter case-control study of CRC patients who underwent surgery at ≥ 80 years old conducted in Japan between 2003 and 2007, both short- and long-term outcomes were compared between right-sided colon cancers (RCCs) and left-sided colorectal cancers (LCCs). RCCs were defined as those located from the cecum to the transverse colon. RESULTS: Among the 1680 patients who underwent curative surgery, 812 and 868 had RCCs and LCCs, respectively. RCCs were more frequent than LCCs in those who were female, had renal comorbidities, and had a history of abdominal surgery. Regarding tumor characteristics, RCCs were larger, invaded more deeply, and were diagnosed as either mucinous or signet ring-cell carcinoma more frequently than LCCs. Regarding the prognosis, patients with RCCs had a significantly longer cancer-specific survival (CS-S) and cancer-specific relapse-free survival (CS-RFS) than those with LCCs. Furthermore, sidedness was determined to be an independent prognostic factor for CS-S and CS-RFS. CONCLUSION: RCCs, which accounted for half of the cases in patients ≥ 80 years old, showed better long-term outcomes than LCCs.

A case of successful management for spontaneous rupture of paraganglioma treated with preoperative transcatheter arterial embolization.

BACKGROUND: Tumors arising from catecholamine-producing chromophil cells in paraganglia are termed paragangliomas (PGLs), which biologically resemble pheochromocytomas (PCCs) that arise from the adrenal glands. Spontaneous rupture of a PGL is rare and can be fatal. Although elective surgery for ruptured PCCs after transcatheter arterial embolization (TAE) has been shown to provide good outcomes, the efficacy of TAE pretreatment for ruptured PGL remains unknown. CASE PRESENTATION: A 65-year-old female with hypertension and tachycardia was diagnosed with a 3-cm PGL located behind the inferior vena cava. The patient was scheduled to undergo an elective surgery with antihypertensive therapy. However, she presented with a chief complaint of abdominal pain and was diagnosed with intratumoral hemorrhage. Urgent TAE was performed that successfully achieved hemorrhage control. After TAE, serum levels of both epinephrine and norepinephrine were within the normal range. Abdominal computed tomography revealed resolving retroperitoneal hematoma. Elective open surgery was performed without significant intraoperative bleeding or fluctuations in blood pressure. CONCLUSION: We report a case of successful preoperative TAE for functional PGL to control intraoperative blood pressure fluctuations and bleeding. Preoperative TAE could be a useful procedure for the surgical preparation of functional PGL, including unruptured cases.

Feasibility, safety, and efficacy of intraoperative magnetic resonance imaging-guided hepatectomy for small hepatocellular carcinoma: A retrospective study.

Advancements in diagnostic modalities, such as enhanced magnetic resonance imaging, provide increased opportunities for identifying small hepatocellular carcinoma that is undetectable on preoperative ultrasonography. Whether it is acceptable to leave these lesions untreated is uncertain. This study aimed to evaluate the safety and efficacy of intraoperative magnetic resonance imaging-guided hepatectomy using new navigation systems. This study was conducted between July 2019 and January 2023. We retrospectively studied the clinicopathological features and prognoses of patients with small hepatocellular carcinoma who underwent curative intraoperative magnetic resonance imaging-guided hepatectomy. We evaluated 23 patients (median age, 75 years), among whom 20 (87.0%) were males. Seven (30.4%) and 15 (65.2%) patients had liver cirrhosis and a history of hepatectomy, respectively. The median size of the target lesions was 9 mm, with a median distance of 6 mm from the liver surface. Despite being undetectable preoperatively on contrast-enhanced ultrasonography, all lesions were identified using intraoperative magnetic resonance imaging. Based on pathological findings, 76.0% of the lesions were malignant. The complete resection rate was 100%, and tumor-free margins were confirmed in 96.0% of the patients. Intraoperative magnetic resonance imaging-guided hepatectomy is safe and effective in identifying and resecting small hepatocellular carcinoma lesions that are undetectable on preoperative ultrasonography.

Effect of genetic polymorphisms of interleukin-1 beta on the microscopic portal vein invasion and prognosis of hepatocellular carcinoma.

BACKGROUND: Several studies have demonstrated a relationship between genetic polymorphisms of interleukin-1 beta (IL-1ß) and cancer development; however, their influence on cancer prognosis is unknown. In the present study, we aimed to evaluate the impact of IL-1ß single nucleotide polymorphisms on the hematogenous dissemination and prognosis of hepatocellular carcinoma. METHODS: We conducted a retrospective cohort study including patients with hepatocellular carcinoma who underwent primary liver resection at our hospital between April 2015 and December 2018. The primary endpoints were overall and recurrence-free survival. Secondary endpoints were microscopic portal vein invasion and number of circulating tumor cells. RESULTS: A total of 148 patients were included, 32 with rs16944 A/A genotype. A/A genotype was associated with microscopic portal vein invasion and number of circulating tumor cells (p = .03 and .04). In multivariate analysis, A/A genotype, alpha-fetoprotein level, and number of circulating tumor cells were associated with microscopic portal vein invasion (p = .01, .01, and <.01). A/A genotype, Child-Pugh B, and intraoperative blood loss were independent predictive factors for overall survival (p = .02, <.01, and <.01). CONCLUSIONS: Our results indicate that the IL-1ß rs16944 A/A genotype is involved in number of circulating tumor cells, microscopic portal vein invasion, and prognosis in HCC.

Impact of a Liver Immune Status Index among Living Liver Transplant Recipients with Hepatocellular Carcinoma.

Introduction: Hepatocellular carcinoma (HCC) is a major global health challenge, being the fifth most prevalent neoplasm and the third leading cause of cancer-related deaths worldwide. Liver transplantation offers a potentially curative approach for HCC, yet the risk of recurrence posttransplantation remains a significant concern. This study investigates the influence of a liver immune status index (LISI) on the prognosis of patients undergoing living-donor liver transplantation for HCC. Methods: In a single-center study spanning from 2001 to 2020, 113 patients undergoing living-donor liver transplantation for HCC were analyzed. LISI was calculated for each donor liver using body mass index, serum albumin levels, and the fibrosis-4 index. This study assessed the impact of donor LISI on short-term recurrence rates and survival, with special attention to its correlation with the antitumor activity of natural killer (NK) cells in the liver. Results: The patients were divided into two grades (high donor LISI, >-1.23 [n = 43]; and low donor LISI, ≤-1.23 [n = 70]). After propensity matching to adjust the background of recipient factors, the survival rates at 1 and 3 years were 92.6% and 88.9% and 81.5% and 70.4% in the low and high donor LISI groups, respectively (p = 0.11). The 1- and 3-year recurrence-free survival were 88.9% and 85.2% and 74.1% and 55.1% in the low and high donor LISI groups, respectively (p = 0.02). Conclusions: This study underscores the potential of an LISI as a noninvasive biomarker for assessing liver NK cell antitumor capacity, with implications for living-donor liver transplantation for HCC. Donor LISI emerges as a significant predictor of early recurrence risk following living-donor liver transplantation for HCC, highlighting the role of the liver antitumor activity of liver NK cells in managing liver malignancies.

Atherosclerosis Deteriorates Liver Ischemia/Reperfusion Injury Via Interferon Regulatory Factor-1 Overexpression in a Murine Model.

BACKGROUND: Abdominal aortic calcification (AAC) is associated with cardiovascular-related mortality, along with an elevated risk of coronary, cerebrovascular, and cardiovascular events. Notably, AAC is strongly associated with poor overall and recurrence free survival posthepatectomy for hepatocellular carcinoma. Despite the acknowledged significance of atherosclerosis in systemic inflammation, its response to ischemia/reperfusion injury (IRI) remains poorly elucidated. In this study, we aimed to clarify the impact of atherosclerosis on the liver immune system using a warm IRI mouse model. METHODS: Injury was induced in an atherosclerotic mouse model (ApoE-/-) or C57BL/6J wild-type (WT) mice through 70% clamping for 1 hour and analyzed after 6 hours of reperfusion. RESULTS: Elevated serum levels of aspartate and alanine aminotransferase, along with histological assessment, indicated considerable damage in the livers of ApoE-/- mice than that in WT mice. This indicates a substantial contribution of atherosclerosis to IRI. Furthermore, T and natural killer (NK) cells in ApoE-/- mouse livers displayed a more inflammatory phenotype than those in WT mouse livers. Reverse transcription-polymerase chain reaction analysis revealed a significant upregulation of interleukin (IL)-15 and its transcriptional regulator, interferon regulatory factor-1 (IRF-1) in ApoE-/- mouse livers compared with that in WT mouse livers. CONCLUSIONS: These findings suggest that in an atherosclerotic mouse model, atherosclerosis can mirror intrahepatic immunity, particularly activating liver NK and T cells through IL-15 production, thereby exacerbating hepatic damage. The upregulation of IL-15 expression is associated with IRF-1 overexpression.

Immunotherapy Using Activated Natural Killer Cells Improves Postoperative Neutrophil-to-Lymphocyte Ratio and Long-Term Prognosis of Living Donor Liver Transplant Recipients With Hepatocellular Carcinoma.

OBJECTIVE: Preoperative neutrophil-to-lymphocyte ratio (NLR) is a well-known prognostic indicator in various malignancies; however, the impact of postoperative NLR on living donor liver transplant (LDLT) recipients is unknown. Immunotherapy with donor liver-derived activated natural killer (NK) cells may improve postoperative NLR by coactivating immune cells or suppressing activated neutrophils. This study aims to clarify the clinical significance of postoperative NLR in recipients after LDLT with HCC and assess whether immunotherapy improves postoperative NLR. METHODS: We conducted a retrospective study of LDLT recipients between 2001 and 2022 to evaluate the clinical significance of postoperative NLR. Furthermore, the correlation between postoperative NLR and the activation marker of infused NK cells was also evaluated. The postoperative NLR was examined 4 weeks after LDLT. RESULTS: The postoperative high NLR group (N = 78) had preoperative lower NLR and higher model for end-stage liver disease and a higher rate of postoperative infection within 30 days after LDLT than the postoperative low NLR group (N = 41). Postoperative high NLR (hazard ratio [HR], 2.62; 95% confidence interval [CI], 1.01-6.79; P = .047) and nontreatment of immunotherapy (HR, 3.10; 95% CI, 1.33-7.22; P < .01) were independent risk factors for poor overall survival in multivariate analysis. Furthermore, the activation marker of infused NK cells is inversely correlated with decreased postoperative NLR. CONCLUSIONS: The higher level of postoperative NLR was independently associated with poor prognosis in patients after LDLT with HCC. Immunotherapy using activated NK cells may improve postoperative NLR and long-term prognosis.

Protocol to evaluate the efficacy and safety of tolvaptan in patients with refractory ascites after liver resection: an open-label, single-arm phase I/II study.

Background: In patients with chronic liver diseases such as cirrhosis, massive ascites after hepatic resection is the cause of prolonged hospitalization and worsening prognosis. Recently, the efficacy of tolvaptan in refractory ascites has been reported; however, there are no reports on the efficacy or safety of tolvaptan for refractory ascites after hepatic resection. This study aims to evaluate the efficacy of early administration of tolvaptan in patients with refractory ascites after hepatic resection. Materials and methods: This is an open-label, single-arm phase I/II study. This study subject will comprise patients scheduled for hepatic resection of a liver tumor. Patients with refractory ascites after hepatic resection (drainage volume on postoperative day 1 ≥5 ml/body weight 1 kg/day) will be treated with tolvaptan. The primary endpoint will include the maximum change in body weight after hepatic resection relative to the preoperative baseline. The secondary endpoints will include drainage volume, abdominal circumference, urine output, postoperative complication rate (heart failure and respiratory failure), number of days required for postoperative weight gain because of ascites to decrease to preoperative weight, change in improvement of postoperative pleural effusion, total amount of albumin or fresh frozen plasma transfusion, type and amount of diuretics used, and postoperative hospitalization days. Conclusion: This trial will evaluate the efficacy and safety of tolvaptan prophylaxis for refractory ascites after hepatic resection. As there are no reports demonstrating the efficacy of tolvaptan prophylaxis for refractory ascites after hepatic resection, the authors expect that these findings will lead to future phase III trials and provide valuable indications for the selection of treatments for refractory postoperative ascites.

Donor Age Correlates With Liver-Resident Natural Killer Cell Activity in Adoptive Immunotherapy Using Donor Liver Natural Killer Cells in Liver Transplantation.

BACKGROUND: Natural killer (NK) cells are involved in innate immunity and have been reported to play an important role in hepatocellular carcinoma recurrence and post-liver transplantation (LT) infection. However, the relationship between donor age and liver-resident NK cell activity remains to be elucidated. METHODS: We successfully performed NK cell immunotherapy in 19 living donor LT recipients to prevent post-LT bloodstream infections. Liver mononuclear cells (LMNCs) were collected from the liver graft perfusate and stimulated with interleukin 2 for 3 days. Liver-resident NK cells were analyzed using flow cytometry and a chromium release assay before and after cell culture. RESULTS: The median donor age was 44 years (range, 24-64 years). The graft weight was 492 g (range, 338-642 g), and the median number of LMNCs was 584 million cells (range, 240-1472 million cells). The proportion of NK cells before and after culture was 22% and 33%, respectively. A significant correlation was found between graft weight and the number of LMNCs. However, no correlation was found between donor age and the number or percentage of NK cells in the liver. Moreover, donor age showed a significant inverse correlation with NKp46 and NKp44 expression before culture and with NKp44, tumor necrosis factor-related apoptosis-inducing ligand, and CD69 expression after culture. CONCLUSION: A significant inverse correlation was observed between donor age and NK cell activity in the liver. This information may be useful for cell therapy during LT.

Association of Abdominal Aortic Calcification With the Postoperative Metabolic Syndrome Components After Liver Transplantation.

BACKGROUND: This study aimed to assess the risk factors for components of metabolic syndrome, such as diabetes mellitus, hypertension, and dyslipidemia, more than a year after liver transplantation. METHODS: This study included 164 patients with liver failure secondary to acute and chronic liver disease or hepatocellular carcinoma who underwent liver transplantation between 2000 and 2019. Univariate and multivariate analyses were performed to identify the risk factors associated with metabolic syndrome components after liver transplantation. RESULTS: The median follow-up period was 10.5 years. Of the 164 patients who underwent liver transplantation, 144 (87.8%) developed components of metabolic syndrome after liver transplantation. The most common cause of liver failure was hepatitis C virus infection (34.1%). The incidence of hepatocellular carcinoma was 36.0%. In univariate analysis, preoperative diabetes mellitus was a significantly more common component of metabolic syndrome than the others. In multivariate analysis, preoperative abdominal aortic calcification was a risk factor for the new onset of all components of metabolic syndrome after liver transplantation, despite the varying degree of calcification at risk of development (odds ratio for diabetes mellitus = 3.487, P = .0069; odds ratio for hypertension = 2.914, P = .0471; odds ratio for dyslipidemia = 3.553, P = .0030). CONCLUSIONS: Preoperative abdominal aortic calcification was significantly associated with the development of each metabolic syndrome component after liver transplantation.

Anti-Donor T-Cell Responses Are Not Necessarily Attenuated During Cytomegalovirus Infection in Kidney Transplant Recipients.

BACKGROUND: Cytomegalovirus (CMV), the most common opportunistic infection of kidney transplantation (KT), is preventable by prophylactic and preemptive antiviral drugs in CMV-immunoglobulin (Ig)G-positive donors. Our preemptive therapy optimized immunosuppressive doses based on mixed lymphocyte response (MLR) results, regardless of preoperative CMV-IgG serostatus pairing. This study used the MLR to compare the anti-donor T-cell responses between CMV antigenemia-positive and -negative cases. METHODS: One hundred patients underwent KT using a cyclosporine (CsA)-based immunosuppressive regimen at Hiroshima University Hospital. CMV antigenemia-positive cells were defined as 4/50,000 CMVpp65-positive cells. T-cell responses to allo-antigens were measured using MLR assays to evaluate patients' anti-donor immune reactivity. After analyzing the proliferation of CD4+ and CD8+ T-cell subsets, the stimulation indices of CD4+ or CD8+ T cells were quantified. The study used no prisoners, and the participants were neither coerced nor paid. The manuscript was created in compliance with the Helsinki Congress and the Declaration of Istanbul. RESULTS: Forty-three patients tested positive for CMV antigenemia within 3 months after KT. No significant differences were found between the CMV antigenemia-positive and -negative groups in the stimulation indices for CD4+ and CD8+ T-cell responses to anti-donor stimulation. However, T-cell responses to third-party stimuli during the postoperative month 1 were significantly less in the CMV antigenemia-positive than -negative group. CONCLUSION: Anti-donor T-cell responses are not necessarily attenuated during CMV infection in KT recipients. In CMV-infected KT recipients, caution should be exercised against inadvertent dose reduction of immunosuppressants.