Association of serum lactate dehydrogenase with prognosis and tumor metabolism in patients with hepatocellular carcinoma treated with atezolizumab plus bevacizumab therapy.

PURPOSE: Treatment outcomes are predicted by analyzing peripheral blood markers such as serum lactate dehydrogenase (LDH). We conducted this study to investigate whether serum LDH levels can predict the prognosis of patients treated with atezolizumab plus bevacizumab (ATZ/BEV) therapy for hepatocellular carcinoma (HCC) and whether LDH levels correlate with metabolic changes. METHODS: We enrolled 66 HCC patients treated with ATZ/BEV. Based on the change in serum LDH levels before and after treatment, the patients were divided into two groups, and the prognosis of each group was examined. Moreover, the association of LDH levels with tumor metabolism was analyzed by fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). RESULTS: There were 32 patients categorized as the LDH-decrease group. Kaplan-Meier survival analysis indicated worse progression-free survival (PFS) in the LDH-increase group than in the LDH-decrease group (p = 0.0029). Multivariate analysis showed that an increase in the LDH level was an independent risk factor for worse PFS (p = 0.0045). The baseline LDH level correlated significantly with a high maximum standardized uptake value of 18F-FDG, according to the PET/CT findings. Transcriptomic analyses of specimens resected after ATZ/BEV therapy showed downregulated mitochondria-related pathways. CONCLUSION: Serum LDH levels are a potential prognostic marker and an indicator of tumor metabolism.

What is the crux of successful living-donor liver transplantation for recipients aged 70 and beyond?

Aim: There is limited evidence regarding the feasibility of living-donor liver transplantation (LDLT) for patients aged over 70. The aims of this study were to assess postoperative outcomes in elderly recipients and to ascertain the potential feasibility and acceptability of LDLT. Methods: Data were collected from 762 recipients, including 26 in the elderly group (aged ≥70) and 736 in the younger group (aged <70), and reviewed even by propensity score matching (PSM). Results: No significant differences were observed in the frequency of postoperative complications between the two groups. Additionally, both groups exhibited a comparable 30-day mortality rate after LDLT (3.9% in both) and similar hospital stays (36 days vs. 40 days). The 1-, 3-, and 5-year graft survival rates in the elderly group were 92.0%, which was comparable to those in the younger group (p = 0.517), as confirmed by PSM. Notably, all donors for elderly patients were the children of the recipients, with an average age of 41.6 years, and grafts from donors aged ≥50 years were not utilized, signifying the use of high-quality grafts. Our inclusion criterion for elderly recipients was strictly defined as an ECOG-PS score of 0-2, which played a pivotal role in achieving favorable postoperative outcomes. Conclusion: LDLT can be performed safely for elderly patients aged 70 years or older, provided they have a preserved PS and receive high-quality grafts from younger donors, inevitably all children of elderly recipients. This approach yields acceptable long-term outcomes. Consequently, age alone should not serve as an absolute contraindication for LDLT.

Prediction of portal venous pressure in living donor liver transplantation: A retrospective study.

Liver transplantation is the definitive treatment for advanced liver cirrhosis with portal hypertension. In Japan, the scarcity of deceased donors leads to reliance on living donors, often resulting in smaller grafts. Managing portal venous pressure (PVP) is critical to prevent fatal posttransplant complications. This study explored the possibility of predicting intraoperative PVP. We analyzed 475 living donor liver transplant cases from 2006 to 2023, excluding those with acute liver failure or prior splenectomy or splenic artery embolization. Patients were divided into a training group (n=425) and a test group (n=50). We evaluated the correlation between preoperative factors and PVP at laparotomy, to predict PVP at laparotomy and closure. The predictive model was validated with the test group data. PVP at laparotomy could be predicted using correlated preoperative factors: prothrombin time ( p <0.001), predicted splenic volume ( p <0.001), and presence of a portosystemic shunt ( p =0.002), as follows: Predicted PVP at laparotomy (mmHg)=25.818 - 0.077×[prothrombin time (%)]+0.004×[predicted splenic volume (ml)] - 2.067×[1: with a portosystemic shunt] ( p <0.001; R=0.346). Additionally, PVP at closure could be predicted using correlated operative factors, including measured PVP at laparotomy, as follows: predicted PVP at closure (mmHg)=14.268+0.149×[measured PVP at laparotomy (mmHg)] - 0.040×[GV/SLV (%)] - 0.862×[1: splenectomy (if yes)] - 3.511×[1: splenic artery ligation without splenectomy (if yes)] ( p <0.001; R=0.339).This study demonstrated the feasibility of predicting intraoperative PVP using preoperative factors in liver transplant patients with decompensated cirrhosis. This predictive approach could refine surgical planning, potentially improving patient outcomes.

Is preoperative weight reduction of living-donor liver transplant recipients and donors harmful to postoperative outcomes?

PURPOSE: Although the incidence of recipients and donors with overweight and obesity is increasing worldwide, few reports have focused on outcomes of preoperative weight reduction (WR) in living-donor liver transplantation (LDLT). Therefore, we examined the outcomes and the impact of WR on the postoperative course. METHODS: We analyzed 217 consecutive LDLT procedures performed from 2017 to 2022. We divided the recipients and donors into a WR group and non-WR group. RESULTS: Twenty-two recipients (10.1%) achieved WR (preoperative recipient WR [RWR] group), reducing their weight by 6.8% ± 6.0% within 2.2 ± 1.4 months with a significant decrease in body mass index (BMI) (P < .0001). The RWR group showed no significant differences in short-term postoperative outcomes (operative factors, postoperative liver function tests, amount of ascites, and morbidity) or in the graft survival rate as a long-term outcome (P = .24) compared with the non-RWR group. Forty-one donors (18.9%) achieved WR (preoperative donor WR [DWR] group), reducing their weight by 9.7% ± 6.3% within 3.2 ± 5.8 months with a significant decrease in BMI (P < .0001). Compared with the non-DWR group, the DWR group showed no significant differences in short-term postoperative outcomes between themselves and recipients or in the graft survival rate (P = .49). Furthermore, WR resulted in an increase to 32 donor-eligible and 6 recipient-eligible patients. CONCLUSION: WR in LDLT recipients and donors had no harmful effect on postoperative outcomes and should lead to increase recipients' chance of undergoing LDLT and to expand the donor pool.

Venous reconstruction using a round ligament-covered prosthetic vascular graft in right­lobe living­donor liver transplantation: a technical report.

PURPOSE: To evaluate the short term-outcomes of venous reconstruction using a round ligament-covered prosthetic vascular graft and assess its effectiveness in the prevention of prosthetic vascular graft migration in right­lobe living donor liver transplantation (LDLT). METHODS AND RESULTS: Thirty patients underwent reconstruction of the middle hepatic vein (MHV) tributaries during right lobe LDLT between January, 2021 and October, 2022. These patients were divided into the autologous vascular graft group (A group, n = 24) and the round ligament-covered prosthetic vascular graft group (RP group, n = 6). The computed tomography (CT) density ratio of the drainage area in the posterior segment of patent grafts was significantly higher in the RP group than in the A group (0.91 vs. 1.06, p = 0.0025). However, the patency rates of reconstructed MHV tributaries in the A and RP groups were 61% and 67%, respectively, with no significant difference between the groups (p = 0.72). Prosthetic vascular graft migration did not occur in the RP group. CONCLUSION: Venous reconstruction using round ligament-covered prosthetic vascular grafts is a feasible and simple method to prevent prosthetic vascular graft migration in right-lobe LDLT.

Impact of electrical muscle stimulation on serum myostatin level and maintenance of skeletal muscle mass in patients undergoing living-donor liver transplantation: Single-center controlled trial.

AIM: Sarcopenia is reportedly associated with a poor prognosis in patients who undergo living-donor liver transplantation (LDLT), most of whom are not able to tolerate muscle strengthening exercise training. Myostatin is one of the myokines and a negative regulator of skeletal muscle growth. The clinical feasibility of an electrical muscle stimulation (EMS) system, which exercises muscle automatically by direct electrical stimulation, has been reported. In this study, we aimed to determine the effect of perioperative application of SIXPAD, which is a type of EMS system, with reference to the serum myostatin and sarcopenia in LDLT patients. METHOD: Thirty patients scheduled for LDLT were divided into a SIXPAD group (n = 16) and a control group (n = 14). In the SIXPAD group, EMS was applied to the thighs twice daily. The serum myostatin was measured in samples obtained before use of SIXPAD and immediately before LDLT. The psoas muscle index (PMI) at the level of the third lumbar vertebra and the quadriceps muscle area were compared on computed tomography images before use of SIXPAD and 1 month after LDLT. RESULTS: The preoperative serum myostatin was found to be higher in LDLT patients than in healthy volunteers and EMS significantly reduced the serum myostatin. Electrical muscle stimulation prevented a postoperative reduction not only in the area of the quadriceps muscles but also in the PMI despite direct stimulation of the thigh muscles. CONCLUSION: Stimulation of muscles by EMS decreases the serum myostatin and helps to maintain skeletal muscle in patients who have undergone LDLT.

Impact of ACSL4 on the prognosis of hepatocellular carcinoma: Association with cancer-associated fibroblasts and the tumour immune microenvironment.

BACKGROUND & AIMS: Recently, the association between hepatocellular carcinoma (HCC) and ferroptosis has been the focus of much attention. The expression of long chain fatty acyl-CoA ligase 4 (ACSL4), a marker of ferroptosis, in tumour tissue is related to better prognosis in various cancers. In HCC, ACSL4 expression indicates poor prognosis and is related to high malignancy. However, the mechanism remains to be fully understood. METHODS: We retrospectively enrolled 358 patients with HCC who had undergone hepatic resection. Immunohistochemistry (IHC) for ACSL4 was performed. Factors associated with ASCL4 expression were investigated by spatial transcriptome analysis, and the relationships were investigated by IHC. The association between ACSL4 and the tumour immune microenvironment was examined in a public dataset and investigated by IHC. RESULTS: Patients were divided into ACSL4-positive (n = 72, 20.1%) and ACSL4-negative (n = 286, 79.9%) groups. ACSL4 positivity was significantly correlated with higher α-fetoprotein (p = .0180) and more histological liver fibrosis (p = .0014). In multivariate analysis, ACSL4 positivity was an independent prognostic factor (p < .0001). Spatial transcriptome analysis showed a positive correlation between ACSL4 and cancer-associated fibroblasts; this relationship was confirmed by IHC. Evaluation of a public dataset showed the correlation between ACSL4 and exhausted tumour immune microenvironment; this relationship was also confirmed by IHC. CONCLUSION: ACSL4 is a prognostic factor in HCC patients and its expression was associated with cancer-associated fibroblasts and anti-tumour immunity.

A successful case of deceased-donor liver transplantation from a donor with Marfan syndrome: a case report.

BACKGROUND: Liver transplantation is the definitive therapy for patients with decompensated cirrhosis. Marfan syndrome is a systemic inheritable connective tissue disease associated with fibrillin-1 gene mutations, which cause abnormalities in connective tissue. Vascular changes due to Marfan syndrome occur mostly in the main vessels due to the high amount of connective tissue within the vessel wall and the high pressure and blood flow to which they are exposed. The incidence of changes in visceral arteries is about 0.42% and usually presents with cystic medial necrosis. This report is the first deceased-donor liver transplantation with a donor with Marfan syndrome with a history of abdominal surgery. CASE PRESENTATION: A patient in his 50s underwent liver transplantation for decompensated alcoholic cirrhosis. The donor, a 50s male with Marfan syndrome, was diagnosed with brain-death due to a cerebral hemorrhage caused by a cerebral aneurysm. The donor's clinical presentation as Marfan syndrome was aortic dissection, with multiple surgical procedures performed from the aortic root to the abdominal aorta. An intraoperative biopsy of the hepatic artery showed no abnormality, so this organ was considered appropriate. The surgery was completed without any problems of the arterial anastomosis. The patient's postoperative course was uneventful, and he was transferred to a hospital for recuperation on the 18th postoperative day. One year after the surgery, the patient is still alive without any complications from the transplantation or arterial problems. CONCLUSIONS: Even if the patient had a history of surgery for vascular anomalies extending to the abdominal aorta due to Marfan syndrome, the patient can be a donor for liver transplantation under appropriate judgment, including intraoperative biopsy.

Clinical significance of mechanistic target of rapamycin expression in vessels that encapsulate tumor cluster-positive hepatocellular carcinoma patients who have undergone living donor liver transplantation.

Background: There is limited published information regarding the expression of mechanistic target of rapamycin (mTOR) in vessels that encapsulate tumor cluster (VETC)-positive hepatocellular carcinoma (HCC). The mTOR inhibitor, everolimus, has been approved as an immunosuppressant for use in HCC patients after living donor liver transplantation (LDLT). Methods: Using a database of 214 patients who underwent LDLT for HCC, we examined the mTOR protein and angiopoietin-2 (Ang-2) in VETC-positive HCC by immunohistochemical staining. The presence of VETC and mTOR expression were evaluated in both primary and recurrent HCC lesions. Results: Forty-three of the 214 patients (20.1%) were VETC-positive, and 29 of these 43 patients (67.4%) expressed mTOR. Relative Ang-2 expression was significantly higher in the mTOR-positive than in the mTOR-negative group (p = 0.037). Thirty-four of the 214 patients experienced HCC recurrence after LDLT; 20 of these were operable. The primary lesions of six of these 20 patients were VETC-positive; five of these six patients also had VETC-positive recurrent lesions (p < 0.001). The expression of mTOR was significantly higher in the VETC-positive lesions (p = 0.0018). Conclusions: We showed that mTOR expression was higher in the VETC-positive primary and recurrent lesions than in the VETC-negative ones.

Impact of TP53-induced glycolysis and apoptosis regulator on malignant activity and resistance to ferroptosis in intrahepatic cholangiocarcinoma.

TP53-induced glycolysis and apoptosis regulator (TIGAR) is an important gene that encodes a regulatory enzyme of glycolysis and reactive oxygen species (ROS) detoxification and is associated with worse prognosis in various cancers. Ferroptosis is a recently identified type of programmed cell death that is triggered by iron-dependent lipid peroxidation. There are no reports on the prognostic impact of TIGAR on intrahepatic cholangiocarcinoma (ICC), and its role in ferroptosis is unclear. Ninety ICC patients who had undergone hepatic resection were enrolled. Immunohistochemical staining for TIGAR was performed. The regulation of malignant activity by TIGAR and the association between ferroptosis and TIGAR were investigated in vitro. Twenty-two (24.4%) patients were categorized into TIGAR-high and -low groups by immunohistochemical staining. There were no noticeable differences in background factors between the two groups, but TIGAR positivity was an independent prognostic factor in disease-free survival (hazard ratio [HR], 2.00; 95% confidence interval [CI], 1.04-3.85, p = 0.0378) and overall survival (HR, 2.10; 95% CI, 1.03-4.30, p = 0.00422) in a multivariate analysis. In vitro, TIGAR knockdown (KD) decreased cell motility (cell proliferation/migration/invasion/colony-forming capabilities) and elevated ROS and lipid peroxidation. This indicated that TIGAR KD induced ferroptosis. TIGAR KD-induced ferroptosis was suppressed using liproxstatin. TIGAR KD decreased the expression of glutathione peroxidase 4, known as factor-suppressing ferroptosis. The combination of TIGAR KD with cisplatin significantly induced more ferroptosis. In conclusion, TIGAR is associated with poor outcomes in ICC patients and resistance to ferroptosis.

Pretreatment eosinophil count predicts response to atezolizumab plus bevacizumab therapy in patients with hepatocellular carcinoma.

AIM: Pretreatment peripheral blood markers have value in predicting the treatment outcome of various cancers. In particular, the eosinophil count has recently gained attention. However, no study has reported the influence of the pretreatment eosinophil count on the outcomes of atezolizumab plus bevacizumab (ATZ/BEV), which is the recommended first-line systemic therapy for unresectable hepatocellular carcinoma (u-HCC). METHODS: We enrolled 114 patients with u-HCC treated with ATZ/BEV (n = 48) or lenvatinib (n = 66). The patients receiving ATZ/BEV or lenvatinib were divided into two groups by calculating the cutoff value of the pretreatment eosinophil count. The groups were compared regarding the clinicopathological characteristics, outcomes, and incidence of adverse events (AEs). RESULTS: Twenty-three of 48 patients (47.9%) who received ATZ/BEV therapy were categorized as the ATZ/BEV-eosinophil-high group, which had better responses than the ATZ/BEV-eosinophil-low group (P = 0.0090). Kaplan-Meier curves revealed a trend toward significantly better progression-free survival (PFS) in the ATZ/BEV-eosinophil-high group than the ATZ/BEV-eosinophil-low group (the median PFS: 4.7 months in the ATZ/BEV-eosinophil-low group vs 12.6 months in the ATZ/BEV-eosinophil-high group; P = 0.0064). Multivariate analysis showed that a low eosinophil count was an independent risk factor for worse PFS after ATZ/BEV therapy (P = 0.0424, hazard ratio: 2.24, 95% confidence interval: 1.02-4.89). AEs (≥ grade 3) were significantly more likely to occur in the ATZ/BEV-eosinophil-high group (P = 0.0285). The outcomes did not significantly differ between the LEN-eosinophil-high group and the LEN-eosinophil-low group. CONCLUSION: A high pretreatment eosinophil count predicted a better response to ATZ/BEV therapy for u-HCC and was associated with the incidence of AEs (≥ grade 3).

Impact of albumin-lymphocyte-platelet-C-reactive protein index as a prognostic indicator of hepatocellular carcinoma after resection: Associated with nuclear factor erythroid 2-related factor 2.

AIM: To investigate the prognostic value of the preoperative albumin-lymphocyte-platelet-C-reactive protein (ALPC) index in patients with hepatocellular carcinoma (HCC) undergoing curative hepatectomy. We also evaluated the relationship between the ALPC index and the phosphorylated nuclear factor erythroid 2-related factor 2 (p-Nrf2) levels. METHODS: Data were analyzed retrospectively from 256 patients who underwent resection for HCC. For cross-validation, patients were divided into the training and testing cohort. We assessed eight combinations of inflammatory markers for predictive value for recurrence. We examined the associations of the ALPC index with recurrence-free survival and overall survival in univariate and multivariate analyses (Cox proportional hazards model). Immunohistochemical staining of p-Nrf2 was performed on tumor samples of 317 patients who underwent hepatic resection for HCC. RESULTS: A high preoperative ALPC index correlated with a high serum albumin concentration, small tumor size, low rate of poor differentiation, solitary tumor, early Barcelona Clinic Liver Cancer stage, and low rate of microscopic intrahepatic metastasis in the training dataset. A high preoperative ALPC index correlated with a high serum albumin concentration, high serum alpha-fetoprotein concentration, small tumor size, a low rate of poor differentiation and a low rate of microscopic intrahepatic metastasis in the testing dataset. A higher preoperative ALPC index was an independent predictor of longer recurrence-free survival and overall survival in the training and testing datasets. A high ALPC index was associated with negative p-Nrf2 expression in HCC tumor cells. CONCLUSIONS: We showed that a high ALPC index was an independent prognostic factor for patients with HCC undergoing curative hepatic resection.

Treatment strategy for hepatocellular carcinoma recurrence in the transplant era: Focusing on the Japan criteria.

PURPOSE: To clarify the Japan criteria (JC), as proposed in 2019, in order to identify the most appropriate treatment methods for hepatocellular carcinoma (HCC) recurrence and assess the feasibility of pre-living donor liver transplantation (LDLT) downstaging within these criteria. METHODS: The subjects of this study were 169 LDLT patients with HCC recurrence. We performed univariate and multivariate analyses of the factors contributing to HCC recurrence after LDLT and clarified the post-transplant outcomes of pre-LDLT downstaging. RESULTS: Univariate and multivariate analysis identified beyond the JC (p = 0.0018) and a neutrophil-to-lymphocyte ratio > 2.01 (p = 0.029) as independent risk factors. Patients who met the JC had significantly higher recurrence-free and overall survival rates after LDLT (p < 0.0001) than those who did not (p = 0.0002). The post-transplant outcomes of patients within the JC after downstaging were significantly better than those of patients beyond the JC (p = 0.034) and equivalent to those within the JC without downstaging. CONCLUSION: Even for HCC recurrence, the JC could play an important role in deciding on the best treatment strategy, and downstaging within the JC had good post-transplant outcomes.

Hand-assisted laparoscopic splenectomy and gastropancreatic fold division: a less-invasive simplified technique of Hassab's procedure for refractory esophagogastric varices.

Some patients with refractory esophagogastric varices require surgery, such as gastric devascularization and splenectomy (Hassab's procedure). However, these patients are at risk of perioperative morbidities when undergoing devascularization to develop collateral vessels. We performed a more simplified procedure, splenectomy, and en bloc gastropancreatic fold division (GPFD) with hand-assisted laparoscopic surgery. Four patients with refractory esophagogastric varices and portal hypertension underwent splenectomy and GPFD. We reviewed patients' perioperative laboratory and morphological data, operative variables, and postoperative outcomes. Esophagogastric varices improved in 3 (75%) of the 4 patients. In one patient, esophageal varices (F1RC0) were observed 3 years after surgery, but they required no treatment and only received follow-up. Treatment with splenectomy and GPFD is not only less invasive than Hassab's procedure but also provides effective outcomes for refractory esophagogastric varices.

Effect of Early Enteral Nutrition on Graft Loss After Living Donor Liver Transplantation: A Propensity Score Matching Analysis.

BACKGROUND: This study aimed to elucidate the effect of early enteral nutrition on graft loss within 12 h after living-donor liver transplantation (LDLT) using propensity score-matching analysis and subsequently examine the risk factors for graft loss after LDLT. METHODS: We retrospectively reviewed the data of 467 LDLT patients who were assigned to the early and non-early groups based on the optimal cutoff value of 12 h for the starting time of early enteral nutrition after LDLT to predict graft loss. RESULTS: The 1-year graft survival rate of the early group before propensity score-matching was 92.1%, whereas the 1-year graft survival rate of the non-early group was 86.2%. There was no significant difference between the 2 groups (P = .067). The incidences of early allograft dysfunction (EAD), small-for-size graft (SFSG) syndrome, acute cellular rejection (ACR), and sepsis were not statistically different between the 2 groups (P = .12, .91, .46, and .056, respectively). After propensity score-matching, the 1-year graft survival rate of the early group was 94.4%, whereas the 1-year graft survival rate of the non-early group was 85.4% (P = .034). The incidences of EAD, SFSG syndrome, and ACR were not statistically different between the 2 groups (P = .43, .81, and .24, respectively). However, the incidence of sepsis was statistically different between the 2 groups (non-early: 10.7% vs early: 3.6%, P = .038). CONCLUSION: Early enteral nutrition within 12 h after LDLT may contribute to better graft survival in LDLT patients by preventing sepsis.

Impact of portal-phase signal intensity of dynamic gadoxetic acid-enhanced magnetic resonance imaging in hepatocellular carcinoma.

PURPOSE: To evaluate the prognostic impact of dynamic gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in patients with hepatocellular carcinoma (HCC). METHODS: We retrospectively reviewed the data of 206 patients with HCC who underwent preoperative Gd-EOB-DTPA-enhanced MRI and hepatectomy and quantitatively evaluated the signal intensity ratio of the tumor to the surrounding liver tissue in the portal phase (SIRPP). We verified the survival rates and assessed the prognostic factors associated with overall survival (OS) and recurrence-free survival (RFS) using SIRPP. RESULTS: Multivariate analysis revealed that the independent predictive factors for poorly-differentiated HCC were α-fetoprotein > 20 ng/mL (hazard ratio [HR]: 3.1909, 95% confidence interval [CI]: 1.3464-7.5622, p = .0084) and SIRPP ≤ 0.85 (HR: 3.7155, 95% CI: 1.521-9.076, p = .004). The 5-year OS and RFS rates in the high and low SIRPP groups were 83.2 and 52.1%, respectively (p < .0001) and 49.7 and 18.5%, respectively (p = .0003). Multivariate analysis revealed that SIRPP ≤ 0.68 was an independent prognostic factor related to OS (HR: 4.4537, 95% CI: 1.6581-11.9626, p = .003). CONCLUSION: The SIRPP of preoperative Gd-EOB-DTPA-enhanced MRI might predict the histological differentiation and prognosis of HCC.

Curative surgery for multiple hepatocellular carcinomas after lenvatinib plus transarterial chemoembolization: a case report.

Surgical therapy following lenvatinib (LEN) plus transarterial chemoembolization (TACE) is a useful therapeutic option for intermediate-stage hepatocellular carcinoma (HCC). A 66-year-old man with a history of hepatitis C was detected four masses in the caudate lobe and segment 6/7 of the liver, with a maximum lesion diameter of 14 cm by computed tomography. The patient was diagnosed with intermediate-stage HCC and received LEN plus TACE. After resuming LEN for 8 weeks, computed tomography showed weakened stained areas of the tumors, and no new lesions. Thus, the patient was evaluated as having a partial response in the modified Response Evaluation Criteria in Solid Tumors. The patient underwent hepatic caudate lobectomy, partial hepatectomy of S6/7, and S6 microwave coagulation therapy for radical resection. The patient is currently alive and recurrence-free at 12 months postoperatively. In patients with multiple HCC lesions, hepatic resection combined with local therapy might be an effective treatment option.

Caution to Poor Adherence With Immunosuppressant Medication That Causes Coma-Onset Autoimmune Encephalitis: A Case Report and Literature Review.

Autoimmune encephalitis after liver transplantation (LT) is a rare disorder. This is because patients are usually in an immunosuppressed state after LT. Here, we report a rare case of autoantibody-negative autoimmune-encephalitis-induced coma after living-donor (LD) LT. A 45-year-old woman who underwent LDLT for primary biliary cholangitis (PBC) was brought to our hospital with the chief complaint of cognitive deficiency and an episode of memory loss. Physical examination, laboratory tests, and cerebrospinal fluid analysis revealed no significant findings. However, diffusion-weighted magnetic resonance imaging showed hyperintensity in the bilateral hippocampus. No autoantibodies associated with autoimmune encephalitis were detected. The diagnosis of antibody-negative autoimmune encephalitis was made on the basis of low immunosuppressive drug levels in the blood (indicative of poor adherence) and the presence of PBC as the autoimmune disease. The patient regained consciousness after intravenous methylprednisolone pulse therapy and plasma exchange. This case highlights that when examining patients with impaired consciousness after LDLT, it is important to consider autoimmune encephalitis as a potential diagnosis.

A third dose of the BNT162b2 mRNA vaccine sufficiently improves the neutralizing activity against SARS-CoV-2 variants in liver transplant recipients.

Introduction: We examined the neutralizing antibody production efficiency of the second and third severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine doses (2nd- and 3rd-dose) and neutralizing activity on mutant strains, including, the Ancestral, Beta and Omicron strains using green fluorescent protein-carrying recombinant SARS-CoV-2, in living-donor liver transplantation (LDLT) recipients. Methods: The patients who were administered vaccines other than Pfizer- BioNTechBNT162b2 and who had coronavirus disease 2019 in this study period were excluded. We enrolled 154 LDLT recipients and 50 healthy controls. Result: The median time were 21 days (between 1st and 2nd vaccination) and 244 days (between 2nd and 3rd vaccination). The median neutralizing antibody titer after 2nd-dose was lower in LDLT recipients than in controls (0.46 vs 1.00, P<0.0001). All controls had SARS-CoV-2 neutralizing antibodies, whereas 39 LDLT recipients (25.3%) had no neutralizing antibodies after 2nd-dose; age at vaccination, presence of ascites, multiple immunosuppressive treatments, and mycophenolate mofetil treatment were significant risk factors for nonresponder. The neutralizing activities of recipient sera were approximately 3-fold and 5-fold lower than those of control sera against the Ancestral and Beta strains, respectively. The median antibody titer after 3rd-dose was not significantly different between recipients and controls (1.02 vs 1.22, p=0.0758); only 5% recipients was non-responder. The neutralizing activity after third dose to Omicron strains were enhanced and had no significant difference between two groups. Conclusion: Only the 2nd-dose was not sufficiently effective in recipients; however, 3rd-dose had sufficient neutralizing activity against the mutant strain and was as effective as that in healthy controls.