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Kun-Ming Chan,1 Yin Lai,1 Hao-Chien Hung,1 Jin-Chiao Lee,1 Chih-Hsien Cheng,1 Yu-Chao Wang,1 Tsung-Han Wu,1 Chen-Fang Lee,1 Ting-Jung Wu,1 Hong-Shiue Chou,1 Ching-Ting Wang,2 Pei-Mei Chai,2 Hsin-Yi Lien,3 Wei-Chen Lee1 1Department of General Surgery and Chang Gung Transplantation Institute, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan; 2Department of Nursing, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan; 3Graduate School of Education, Ming Chuan University, Taoyuan, TaiwanCorrespondence: Kun-Ming Chan, Department of General Surgery and Chang Gung Transplantation Institute, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, No. 5 Fu-Hsing Street, Gui-Shan District, Taoyuan City, 33305, Taiwan, Tel +886-3-3281200 Ext 3366, Fax +886-3-3285818, Email chankunming@cgmh.org.twBackground: Tyrosine kinase inhibitors (TKIs) remain the primary therapeutic option for patients with advanced-stage hepatocellular carcinoma (HCC). However, the selection of a suitable TKI is an issue in real-world clinical practice. Thus, this study aimed to identify patients most likely to benefit from lenvatinib treatment.Methods: A retrospective review of 143 patients with unresectable advanced-stage HCC treated with lenvatinib between January 2020 and December 2021 was performed. Outcomes related to lenvatinib treatment were measured, and the clinical parameters affecting prognosis were analyzed.Results: Overall, the median time of progression-free survival (PFS) and overall survival (OS) were 7.1 months and 17.7 months, respectively. Prognostic analyses found that Child-Pugh score > 5 (hazard ratio [HR] = 2.43, 95% confidence interval [CI] = 1.55– 3.80, p = 0.001) was a significant factor affecting the PFS of HCC after lenvatinib treatment. Child-Pugh score > 5 (HR = 2.12, 95% CI = 1.20– 3.74, p = 0.009), body weight ≥ 60 kg (HR = 0.54, 95% CI = 0.32– 0.90, p = 0.020), and additional trans-arterial chemoembolization (TACE) treatment (HR = 0.38, 95% CI = 0.21– 0.70, p = 0.003) were significant prognostic factors for OS. However, early α-fetoprotein reduction was not significantly correlated with patient outcomes. Additionally, patients with pre-treatment neutrophil-lymphocyte ratio > 4.07 showed a significant worse PFS and OS than other patients.Conclusion: The outcome of patients with advanced-stage HCC remains poor. However, the host condition, including good physical status and better functional liver preservation, largely affected the outcome of patients receiving lenvatinib treatment. Moreover, additional locoregional therapy for intrahepatic HCC, other than TKI treatment, can be considered in certain patients to achieve a favorable outcome.Keywords: hepatocellular carcinoma, advanced-stage, tyrosine kinase inhibitor, lenvatinib, outcome

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.

The severe form of acute exacerbation of hepatitis B during pregnancy is a rare but life-threatening condition for both the mother and the fetus. A 32-year-old pregnant woman at 10 weeks of gestation was diagnosed with acute decompensated liver failure due to acute exacerbation of hepatitis B. The Model for End-stage Liver Disease score was up to 37. The patient was managed carefully with antiviral treatment, fluid resuscitation, correction of coagulopathy, close monitoring of hepatic function, and regular assessment of the fetus. She was transplanted with a deceased liver at 14 weeks and 1 day of gestation. With careful post-transplant care and avoidance of medication with risk of miscarriage and teratogenicity, a healthy baby was delivered at 39 weeks and 1 day of gestation. Herein, we report this critical condition of pregnancy that was complicated with liver failure due to acute exacerbation of hepatitis B, but had favorable outcomes for both the mother and the baby after liver transplantation.

BACKGROUND AND OBJECTIVES Precise prognostic prediction for an individual hepatocellular carcinoma (HCC) patient before and after liver resection is important. We aimed to establish simple prognostic models to predict disease-free survival (DFS) for these patients. METHODS Six hundred and ninety-eight HCC patients with liver resections were reviewed. Preoperative (model 1) and postoperative (model 2) nomogram-based scoring systems were constructed by multivariate analyses, and DFS was estimated. RESULTS Among 698 patients, 490 (70.2%) patients had tumor recurrence at a median follow-up of 84.4 months. Risk factors of tumor recurrence in model 1 included viral hepatitis, platelet count, albumin, indocyanine green retention rate, multiplicity of tumor, and radiologic total tumor volume (TTV). Prognostic variables identified in model 2 were viral hepatitis, platelet count, multiplicity of tumor, cirrhosis, microvascular invasion, and pathologic TTV. By nomogram in model 1, the patients were classified into three groups with 5-year DFS of 61.0%, 35.7%, and 21.1%, respectively (P

No prognostic models specific to hepatocellular carcinoma patients receiving surgical resection have been considered strong and convincing enough for survival prediction thus far, and there are no models including only preoperative predictors. We derived a nomogram to predict disease-free survival in a previous study.To simplify our score and compare research outcomes among other scoring systems.We retrospectively reviewed data from 1106 patients with hepatocellular carcinoma who underwent liver resection at the Linkou Chang Gung Memorial Hospital between April 2003 and December 2012. Multivariate analyses were conducted to identify the significant survival predictors. Homogeneity, Harrell's C-index, and Akaike information criterion were compared between our score, AJCC 8Among the 1106 patients, 731 (66.1%) had tumor recurrence at a median follow-up of 83.9 mo. Five risk factors were identified: platelet count, albumin level, indocyanine green retention rate, multiplicity, and radiologic total tumor volume. Patients were divided into three risk groups, and the 5-year survival rates were 61.7%, 39%, and 25.7%, respectively. The C-index was 0.617, which was higher than the Tokyo score (0.613) and the Taipei Integrated Scoring System (0.562) and equal to the value of the AJCC 8The modified score provides an easier method to predict survival. Appropriate treatment can be planned preoperatively by dividing patients into risk groups.

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.

BACKGROUND Duct-to-duct biliary reconstruction has been increasingly used in living-donor liver transplantation. Information regarding dual duct-to-duct biliary anastomoses is limited. We present the largest case series to date on the use of the cystic and common hepatic ducts as dual-ductal anastomosis, along with long-term follow-up results. MATERIAL AND METHODS In this study, 740 patients underwent right-lobe living-donor liver transplantation; 56 of them were documented as dual-ductal anastomoses. We analyzed recipient and donor characteristics, surgical procedures, appearance of biliary complications, corresponding interventions, and long-term biliary outcomes. RESULTS Cystic and common hepatic ducts were utilized in 56 cases of dual-ductal biliary reconstruction, which we categorized into 2 types: A (78.6%), in which the right anterior intrahepatic duct was anastomosed to the common hepatic duct and the right posterior intrahepatic duct to the cystic duct; and B (21.4%), which was the reverse of A. After a median follow-up period of 46.4 months, 23 patients (41.1%) experienced complications, including biliary leakage and biliary stricture. However, after aggressive intervention (patent biliary anastomosis in most of them), 50 of 56 patients (89.3%) had patent biliary anastomosis and restored normal liver function at the end of follow-up. A small graft (graft-to-recipient weight ratio0.9%) was the only predictor of biliary complications after multivariate analysis. CONCLUSIONS Dual-ductal biliary reconstruction in adult right-lobe living-donor liver transplantation is challenging but feasible. Our findings support the use of the cystic duct for reconstruction in selected patients. Good long-term results can be achieved with adequate management of patients with biliary complications.

Acute liver failure is life-threatening and has to be treated by liver transplantation urgently. When deceased donors or ABO-compatible living donors are not available, ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) becomes the only choice. How to prepare ABO-I LDLT urgently is an unsolved issue. A quick preparation regimen was designed, which was consisted of bortezomib (3.5 mg) injection to deplete plasma cells and plasma exchange to achieve isoagglutinin titer ≤ 1: 64 just prior to liver transplantation and followed by rituximab (375 mg/m

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.

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. Abstract 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.

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.

Background The outcomes and management of hepatocellular carcinoma (HCC) have undergone several evolutionary changes. This study aimed to analyze the outcomes of patients who had undergone liver resection for HCC with portal vein tumor thrombosis (PVTT) in terms of the evolving era of treatment. Materials and methods A retrospective analysis of 157 patients who had undergone liver resection for HCC associated with PVTT was performed. The outcomes and prognostic factors related to different eras were further examined. Results Overall, 129 (82.1%) patients encountered HCC recurrence after liver resection, and the median time of recurrence was 4.1 months. Maximum tumor size ≥ 5 cm and PVTT in the main portal trunk were identified as the major prognostic factors influencing HCC recurrence after liver resection. Although the recurrence-free survival had no statistical difference between the two eras, the overall survival of patients in the second era was significantly better than that of the patients in the first era (p = 0.004). The 1-, 2-, and 3-year overall survival rates of patients in the second era were 60.0%, 45.7%, and 35.8%, respectively, with a median survival time of 19.6 months. Conclusion The outcomes of HCC associated with PVTT remain unsatisfactory because of a high incidence of tumor recurrence even after curative resection. Although the management and outcomes of patients with HCC and PVTT have greatly improved over the years, surgical resection remains an option to achieve a potential cure of HCC in well-selected patients.

Background. Liver resection is a primary curative treatment for early stage hepatocellular carcinoma (HCC), but the outcomes are impeded by early tumor recurrence. This study aimed to establish a prediction model which could predict tumor recurrence outside the Milan criteria prior to liver resection.Methods. A cohort of 891 HCC patients who had curative liver resections were reviewed. HCC recurrence was divided into 4 groups: early recurrence inside the Milan criteria (ER-MI), early recurrence outside the Milan criteria (ER-MO), late recurrence inside the Milan criteria (LR-MI), and late recurrence outside the Milan criteria (LR-MO). The risk factors of ER-MO were analyzed to establish a prediction model.Results: During a median follow-up of 83.4 months, 589 (66.1%) patients developed recurrent HCC. Among 589 patients, 276 (31.0%), 86 (9.6%), 46 (5.2%) and 181(23.3%) patients were in ER-MO, ER-MI, LR-MO and LR-MI groups, respectively. In multivariate analysis of pre-operative factors, large tumors, non-single tumors, high α-fetoprotein level, high neutrophil-to-lymphocyte ratio and high indocyanine green retention were the independent predictors of ER-MO. By adjusting the weight of independent risk factors into scores and stratifying patients into class I, II, III and IV according to score 0, 2-6, 7-10 and ≥11, ER-MO events at 24 months were 12.5%, 22.5%, 45.4% and 66.3% for class I, II, III and IV, respectively (P< 0.05).Conclusions. A risk scoring model was built and could predict ER-MO based on pre-operative factors. This scoring model would be helpful for sharing the decision marking of treatments with patients.

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 &lt, 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 &lt, 4 indicated disease-control, and can be applied as biomarkers to select the right patients to receive this costly therapy.

Background Therapeutic effect and immunosuppressor cell alteration in adding transcatheter arterial chemoembolization (TACE) to sorafenib for advanced stage hepatocellular carcinoma (HCC) remain unclear. Aims To examine the therapeutic effect and immunosuppressor cell alteration in adding TACE to sorafenib. Methods Forty‐four advanced stage HCC patients were divided into group A (n = 17) treated by sorafenib (400‐600 mg/day) alone and group B patients (n = 27) treated by sorafenib and TACE. The frequency of regulatory T‐cells and myeloid‐derived suppressor cells (MDSC), and patients' outcomes were examined. Advanced HCC patients' survival was improved by adding TACE to sorafenib if N/L was reduced from ≥2.5 to

Objective Cytomegalovirus (CMV) infection has a significant negative impact on liver transplant (LT) recipients. We aimed to evaluate the efficacy of real‐time DNA quantitative polymerase chain reaction (qPCR) in the early detection of CMV and predicting post‐transplant outcomes. Materials and Methods This was a retrospective study that enrolled a total of 49 adult LT recipients between December 2016 and October 2019. Serial CMV qPCR were tested weekly. We used operating characteristic curve analysis to quantify qPCR replication numbers to decide the optimal threshold to predict posttransplant complications and overall survival. Results The optimal cut‐off value of 180 copies/ml (=164 IU/ml) was determined. We had 40 patients in the low qPCR group (, We described that high DNA replication (164 IU/ml) is an indicator of developing major postliver transplant complications. Implementing preemptive treatment for this high‐risk group is mandatory to improve outcomes after liver transplantation.

Acute kidney injury (AKI) is a common complication of perinatal asphyxia and is associated with poorer short-term and long-term outcomes. This retrospective study describes the incidence of AKI in asphyxiated neonates who have received therapeutic hypothermia using the proposed modified Kidney Diseases: Improving Global Outcomes (KDIGO) definition and investigates clinical markers that would allow earlier recognition of at-risk neonates. We included asphyxiated neonates who underwent therapeutic hypothermia between the period of January 2011 and May 2018 in our study. The serum creatinine levels within a week of birth were used in establishing AKI according to the modified KDIGO definition. Demographic data, resuscitation details, laboratory results and use of medications were collected and compared between the AKI and non-AKI groups to identify variables that differed significantly. A total of 66 neonates were included and 23 out of them (35%) were found to have AKI. The neonates with AKI had a lower gestational age (p = 0.006), lower hemoglobin level (p = 0.012), higher lactate level before and after therapeutic hypothermia (p = 0.013 and 0.03 respectively) and higher troponin-I level after therapeutic hypothermia (p p = 0.025). The receiver operating curve showed that troponin-I after therapeutic hypothermia had an area under curve of 0.858 at the level 0.288 ng/ml. Our study concludes that the incidence of AKI among asphyxiated newborns who received therapeutic hypothermia is 35% and an elevated troponin-I level after therapeutic hypothermia is independently associated with an increased risk of AKI in asphyxiated newborns.

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 &plusmn, 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 &plusmn, 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.

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 (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.

Liver transplantation has become a routine operation in many transplantation centers worldwide. However, liver graft availability fails to meet patient demands. Split liver transplantation (SPLT), which divides a deceased donor liver into 2 partial liver grafts, is a promising strategy for increasing graft availability for transplantation and ameliorating organ shortage to a certain degree. However, the transplantation community has not yet reached a consensus on SPLT because of the variable results. Specifically, SPLT for 2 adult recipients using full right/left hemi-liver grafts is clinically more challenging in terms of surgical technique and potential postoperative complications. Therefore, this review summarizes the current status of SPLT, focusing on the transplantation of adult recipients. Furthermore, the initiation of the SPLT program, donor allocation, surgical aspects, recipient outcomes, and obstacles to developing this procedure will be thoroughly discussed. This information might help provide an optimal strategy for implementing SPLT for 2 adult recipients among current transplantation societies. Meanwhile, potential obstacles to SPLT might be overcome in the near future with growing knowledge, experience, and refinement of surgical techniques. Ultimately, the widespread diffusion of SPLT may increase graft availability and mitigate organ donation shortages.

Background. A combination of antihepatitis B immunoglobulin and antiviral agents is the most common regimen for prophylaxis of hepatitis B recurrence after liver transplantation. However, hepatitis B recurrence still happens. The significance of hepatitis B recurrence is less mentioned. Materials. Forty-eight of the 313 hepatitis B liver transplant recipients having hepatitis B recurrence were included in this study. The patients were divided into group A, the patients transplanted for hepatitis B-related liver failure, and group B, the patients transplanted for hepatitis B-related cirrhosis and HCC. The clinical manifestations after hepatitis B recurrence were recorded. Results. Among the 48 patients with hepatitis B recurrence, 23 patients were in group A and 25 patients in group B. The age was 51.6±9.4 years in group A and 52.8±6.4 in group B (p=0.869). The MELD score prior to transplantation was 23.1±9.9 in group A patients and 12.9±5.6 in group B patients (p<0.001). The median (interquartile) interval from transplantation to hepatitis B recurrence was 10 (2-19) months for group A patients and 13 (8.5-35) months for group B patients (p=0.051). After hepatitis B recurrence, the liver function was almost normal in both groups. In group B patients, 10 patients had HCC recurrence with 7 of 10 patients having hepatitis B recurrence earlier than HCC recurrence. The interval between hepatitis B and HCC recurrence was 1 to 15 months. The 1-, 3-, and 5-year survival rates were 82.6%, 73.9%, and 69.0%, respectively, for group A patients and 96%, 76%, and 68%, respectively, for group B patients (p=0.713). Conclusion. The patients have uneventful liver function under antiviral agent while hepatitis B recurred. For the patients having HCC prior to transplantation, close monitoring of HCC recurrence is necessary if hepatitis B recurs.

Background Neutrophil-lymphocyte ratio (NLR) represents a pro-tumor inflammatory environment and host immunity. The aim of this study was to examine the effect of subsequent NLR for hepatocellular carcinoma (HCC) after liver resection. Methods A total of 672 patients had liver resection for HCC were included in this study. NLR at diagnosis of HCC and HCC recurrence were collected. NLR at 2.5 was used as cut-off value to calculate its prognostic effect. Results According to NLR cut-off value, the patients with NLR >2.5 had larger tumor size, higher histology grade, and higher rates of tumor multiplicity and vascular invasion. After a median follow-up of 76.3 months, 437 (65.0%) patients had tumor recurrence. The 1-, 3- and 5-year recurrence-free survival were 77.4%, 55.2% and 44.8% in NLR ≤2.5 group, compared to 64.1%, 45.2% and 35.5% in NLR >2.5 group (P = 0.016). When patients had tumor recurrence, 5-year post-recurrent survival was best in the patients staying with NLR ≤2.5 all the time and decreased from 45.9% to 24.6% if NLR was ≤2.5 at resection and became >2.5 at recurrence (P = 0.013). Conclusion High NLR was an independent unfavorable prognostic factor. Subsequent change of NLR between liver resection and HCC recurrence could predict post-recurrent survival.

Liver resection for hepatocellular carcinoma (HCC) is associated with high recurrence rates. Adequate resection margin which is carried out by surgeons may reduce tumor recurrence. Nevertheless, the margin width remains controversial particularly in cirrhotic patients where optimal parenchymal preservation is necessary. This study aims to find a reference for proposing the resection margin when liver resection is planning. Totally, 534 patients who received liver resection for HCC were included. The clinical profiles of the patients, tumor characteristics and patients’ survival were all collected. The patients were classified according to resection margin (200 ng/ml), then survival was calculated. Most of the patients had hepatitis B (52.4%) and hepatitis C (24.0%) infection. Multivariate analysis showed that narrow resection margin (200 ng/ml, resection margin had to be extended to ≥1 cm to improve 5-year disease-free survival from 33.9 months to 48.8 months (P = .012). When the patients meeting AFP 200 ng/ml with margin ≥1 cm were compared, their survival rates were not different. Adequate resection margin can be guided by pre-operative AFP levels. Tumor-free margin is enough for patients with normal AFP level. A resection margin ≥0.5 cm is advised for the patients with AFP between 15 and 200 ng/ml, and ≥1 cm for the patients with AFP over 200 ng/ml.