Risk factors for pre-transplantation bacteremia in adults with end-stage liver disease: Effects on outcomes of liver transplantation.

BACKGROUND AND AIM: Limited data are available regarding pre-liver transplantation (LT) bacteremia in adults with end-stage liver disease. In this study, we investigated the risk factors independently associated with pre-LT bacteremia and their effects on clinical outcomes of LT. METHODS: This retrospective study performed between 2010 and 2021 included 1287 LT recipients. The study population was categorized into patients with pre-LT bacteremia and those without pre-LT infection. Pre-LT bacteremia was defined as bacteremia detected within 90 days before LT. RESULTS: Among 1287 LT recipients, 92 (7.1%) developed pre-LT bacteremia. The mean interval between bacteremia and LT was 28.3 ± 19.5 days. Of these 92 patients, seven (7.6%) patients died after LT. Of the 99 microorganisms isolated in this study, gram-negative bacteria were the most common microbes (72.7%). Bacteremia was mainly attributed to spontaneous bacterial peritonitis. The most common pathogen isolated was Escherichia coli (25.2%), followed by Klebsiella pneumoniae (18.2%), and Staphylococcus aureus (15.1%). Multivariate analysis showed that massive ascites (adjusted odds ratio [OR] 1.67, 95% confidence Interval [CI] 1.048-2.687) and a prolonged international normalized ratio for prothrombin time (adjusted OR 1.13, 95% CI 1.074-1.257) were independent risk factors for pre-LT bacteremia in patients with end-stage liver disease. Intensive care unit and in-hospital stay were significantly longer, and in-hospital mortality was significantly higher among LT recipients with pre-LT bacteremia than among those without pre-LT infection. CONCLUSIONS: This study highlights predictors of pre-LT bacteremia in patients with end-stage liver disease. Pre-LT bacteremia increases the post-transplantation mortality risk.

The outcomes and biliary complications of a staged biliary reconstruction in living donor liver transplantation: a propensity score matched analysis.

BACKGROUND: Uncontrolled massive bleeding and bowel edema are critical issues during liver transplantation. Temporal intra-abdominal packing with staged biliary reconstruction (SBR) yields acceptable outcomes in deceased donor liver transplantation; however, data on living donor liver transplantation (LDLT) are scarce. METHODS: A retrospective analysis of 1269 patients who underwent LDLT was performed. After one-to-two propensity score matching, patients who underwent LDLT with SBR were compared with those who underwent LDLT with one-stage biliary reconstruction (OSBR). The primary outcomes were graft survival (GS) and overall survival (OS), and the secondary outcomes were postoperative biliary complications. RESULTS: There were 55 and 110 patients in the SBR and OSBR groups, respectively. The median blood loss was 6500 mL in the SBR and 4875 mL in the OSBR group. Patients receiving SBR-LDLT had higher incidence of sepsis (69.0% vs. 43.6%; P < 0.01) and intra-abdominal infections (60.0% vs. 30.9%; P < 0.01). Biliary complication rates (14.5% vs. 19.1%; P = 0.47) and 1-and 5-year GS (87.27%, 74.60% vs. 83.64%, 72.71%; P = 0.98) and OS (89.09%, 78.44% vs. 84.55%, 73.70%; P = 0.752) rates were comparable between the two groups. CONCLUSIONS: SBR could serve as a life-saving procedure for patients undergoing complex critical LDLT, with GS, OS, and biliary outcomes comparable to those of OSBR.

Tumor Necrosis Is an Indicator of Poor Prognosis Among Hepatoma Patients Undergoing Resection.

INTRODUCTION: Tumor necrosis has been associated with poor prognosis in hepatocellular carcinoma (HCC) patients undergoing liver resection (LR). However, more evidence is needed to clarify this issue. METHODS: Patients who underwent upfront LR between 2010 and 2018 for newly diagnosed HCC without undergoing neoadjuvant therapy were enrolled in this retrospective study. Tumor necrosis was classified as present or absent according to retrospective examinations. The association between tumor necrosis, pathologic characteristics, overall survival (OS), and recurrence-free survival (RFS) were analyzed. RESULTS: Among 756 patients who underwent LR for HCC, tumor necrosis was present in 279 (36.9%) patients. Compared with patients without tumor necrosis, patients with tumor necrosis had higher proportions of tumors sized >5.0 cm (P < 0.001), multiple tumors (P < 0.001), microvascular or macrovascular invasion (P < 0.001), poorly differentiated or undifferentiated tumors (P < 0.001), and T stage 3 or 4 (P < 0.001) on pathological examination. The presence of tumor necrosis was associated with worse OS and RFS compared with the absence of tumor necrosis: 5-y OS was 56% versus 78% (P < 0.001); 5-y RFS was 42% versus 55% (P < 0.001). In multivariate analysis, the presence of tumor necrosis was an independent factor associated with worse OS (hazard ratio: 1.956; 95% confidence interval: 1.409-2.716; P < 0.001) and RFS (hazard ratio: 1.422; 95% confidence interval: 1.085-1.865; P = 0.011). CONCLUSIONS: Tumor necrosis was associated with worse OS and RFS among patients who underwent LR for HCC.

Overall survival among patients who undergo resection does not differ significantly between T1a and T1b hepatocellular carcinoma based on the 8th American Joint Commission on Cancer.

PURPOSE: The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for hepatocellular carcinoma (HCC) has been used since 2018. However, whether any significant difference in overall survival (OS) exists between patients with T1a and T1b HCC who undergo resection has been controversial. We aim to clarify this issue. METHODS: We consecutively enrolled newly diagnosed HCC patients who underwent liver resection (LR) from 2010 to 2020 at our institution. OS was estimated using the Kaplan-Meier method and compared using log-rank tests. Prognostic factors for OS were identified by multivariate analysis. RESULTS: This study enrolled 1250 newly diagnosed HCC patients who underwent LR. No significant differences in OS were identified between patients with T1a and T1b tumors among all patients (p = 0.694), cirrhotic patients (p = 0.753), non-cirrhotic patients (p = 0.146), patients with alpha-fetoprotein (AFP) > 20 ng/ml (p = 0.562), patients with AFP ≤ 20 ng/ml (p = 0.967), patients with Edmondson grade 1 or 2 (p = 0.615), patients with Edmondson grade 3 or 4 (p = 0.825), patients positive for hepatitis B surface antigen (HBsAg; p = 0.308), in patients positive for anti-hepatitis C virus (HCV) antibody (p = 0.781), or patients negative for both HBsAg and anti-HCV antibody (p = 0.125). Using T1a as the reference, multivariate analysis showed that T1b is not a significant predictive factor for OS (hazard ratio (HR): 1.338; 95% confidence interval (CI):0.737-2.431; p = 0.339). CONCLUSION: No significant difference in OS was observed between patients who underwent LR to treat T1a and T1b HCC tumors.

Radiographic tumor burden score is useful for stratifying the overall survival of hepatocellular carcinoma patients undergoing resection at different Barcelona Clinic Liver Cancer stages.

PURPOSE: The Barcelona Clinic Liver Cancer (BCLC) staging system has been recommended for prognostic prediction. However, prognosis is variable at different BCLC stages. We aimed to evaluate whether the radiographic tumor burden score (TBS) could be used to stratify prognosis in different BCLC stages. METHODS: Hepatocellular carcinoma (HCC) patients undergoing liver resection (LR) at BCLC-0, -A, or -B stage in our institution in 2007-2018 were divided into derivation and validation cohorts. Overall survival (OS) was analyzed according to the TBS and BCLC stage. TBS cutoff values for OS were determined with X-tile. RESULTS: Of the 749 patients in the derivation cohort, 138 (18.4%) had BCLC-0, 542 (72.3%) BCLC-A, and 69 (9.2%) BCLC-B HCC; 76 (10.1%) had a high TBS (> 7.9), 477 (63.7%) a medium TBS (2.6-7.9), and 196 (26.2%) a low TBS (< 2.6). OS worsened progressively with increasing TBS in the cohort (p < 0.001) and in BCLC-A (p = 0.04) and BCLC-B (p = 0.002) stages. Multivariate analysis showed that the TBS was associated with OS of patients with BCLC-A (medium vs. low TBS: hazard ratio [HR] = 2.390, 95% CI = 1.024-5.581, p = 0.04; high vs. low TBS: HR = 3.885, 95% CI = 1.443-10.456, p = 0.007) and BCLC-B (high vs. medium TBS: HR = 2.542, 95% CI = 1.077-6.002, p = 0.033) HCC. The TBS could also be used to stratify the OS of patients in the validation cohort (p < 0.001). CONCLUSION: The TBS could be used to stratify the OS of the entire cohort and BCLC stages A and B of HCC patients undergoing LR.

Overexpression of miR-4669 Enhances Tumor Aggressiveness and Generates an Immunosuppressive Tumor Microenvironment in Hepatocellular Carcinoma: Its Clinical Value as a Predictive Biomarker.

Accumulating evidence suggests the involvement of tumor-derived exosomes in the development and recurrence of hepatocellular carcinoma (HCC). We previously identified miR-4669 as a highly expressed microRNA in circulating exosomes obtained from patients with post-transplant HCC recurrence. This study aimed to explore how overexpression of miR-4669 affects HCC development and recurrence. The impact of miR-4669 overexpression in Hep3B cells on tumor cell behavior and the tumor microenvironment was evaluated in vitro. In addition, the clinical value of exosomal miR-4669 for the prediction of treatment response to HCC downstaging therapies and following post-transplant HCC recurrence was explored. Overexpression of miR-4669 enhanced migration ability and led to acquired sorafenib resistance with an elevation of sirtuin 1 and long noncoding RNA associated with microvascular invasion. Active release of tumor-derived exosomes and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) contributed to generating an immunosuppressive tumor microenvironment through the induction of M2 macrophage polarization. The retrospective analysis demonstrated the clinical value of exosomal miR-4669 for predicting treatment response to HCC downstaging therapies and for risk assessment of post-transplant HCC recurrence. In summary, the present data demonstrate the impact of exosomal miR-4669 on HCC recurrence through the enhancement of tumor aggressiveness and generation of an immunosuppressive tumor microenvironment.

Use of blood oxygen level-dependent magnetic resonance imaging to detect acute cellular rejection post-liver transplantation.

OBJECTIVES: Acute cellular rejection (ACR) is a major immune occurrence post-liver transplant that can cause abnormal liver function. Blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) can be used to evaluate liver disease, but it has not been utilized in the diagnosis of ACR post-liver transplant. Therefore, the purpose of this study is to evaluate the diagnostic performance of BOLD MRI and to monitor treatment response in recipients with ACR. METHODS: This prospective study was approved by the local institutional review board. Fifty-five recipients with highly suspected ACR were enrolled in this study. Each patient underwent hepatic BOLD MRI, blood biochemistry, and biopsy before treatment. Of 55 patients, 19 recipients with ACR received a follow-up MRI after treatment. After obtaining the R2* maps, five regions-of-interest were placed on liver parenchyma to estimate the mean R2* values for statistical analysis. Receiver operating characteristic curve (ROC) analysis was performed to assess the diagnostic performance of R2* values in detecting patients with ACR. RESULTS: The histopathologic results showed that 27 recipients had ACR (14 mild, 11 moderate, and 2 severe) and their hepatic R2* values were significantly lower than those of patients without ACR. ROC analysis revealed that the sensitivity and specificity of the R2* values for detection of ACR were 82.1% and 89.9%, respectively. Moreover, the R2* values and liver function in patients with ACR significantly increased after immunosuppressive treatment. CONCLUSION: The non-invasive BOLD MRI technique may be useful for assessment of hepatic ACR and monitoring of treatment response after immunosuppressive therapy. KEY POINTS: • Patients with acute cellular rejection post-liver transplant exhibited significantly decreased R2* values in liver parenchyma. • R2* values and liver function were significantly increased after immunosuppressive therapy. • R2* values were constructive indicators in detecting acute cellular rejection due to their high sensitivity and specificity.

Extremity risk factors of sepsis for gastrointestinal endoscopy in patients with liver cirrhosis.

BACKGROUND: Liver cirrhosis is a well-known risk factor of sepsis after emergent gastrointestinal (GI) endoscopy. Elective GI endoscopy before living donor liver transplantation (LDLT), however, may also carry the septic risk among these patients. METHODS: This retrospective study reviewed the medical records of 642 cirrhotic recipients who underwent GI endoscopy from 2008 to 2016. We analyzed the incidence and risk factors of post-endoscopy sepsis during 2008-2012 (experience cohort). Our protocol changed after 2013 (validation cohort) to include antibiotic prophylaxis. RESULTS: In experience cohort, 36 cases (10.5%) of the 342 LDLT candidates experienced sepsis within 48 h after endoscopy. The sepsis rate was significantly higher in patients with hepatic decompensation than patients without (22.2% vs. 9.6% vs. 2.6% in Child C/B/A groups respectively; ×2 = 20.97, P < 0.001). Using multivariate logistic regression analysis, the factors related to post-endoscopy sepsis were the Child score (OR 1.46; 95% CI 1.24-1.71), Child classes B and C (OR 3.80 and 14.13; 95% CI 1.04-13.95 and 3.97-50.23, respectively), hepatic hydrothorax (OR 4.85; 95% CI 1.37-17.20), and use of antibiotic prophylaxis (OR 0.08; 95% CI 0.01-0.64). In validation cohort, antibiotics were given routinely, and all cases of hepatic hydrothorax (n = 10) were drained. Consequently, 4 (1.3%) episodes of sepsis occurred among 300 LDLT candidates, and the incidence was significantly lower than before (1.3% vs. 10.5%, P < 0.001). CONCLUSIONS: Patients with decompensated cirrhosis and hepatic hydrothorax have higher risk of sepsis following endoscopy. In advanced cirrhotic patients, antibiotic prophylaxis and drainage of hydrothorax may be required to prevent sepsis before elective GI endoscopy.

Transferability and interpretability of the sepsis prediction models in the intensive care unit.

BACKGROUND: We aimed to develop an early warning system for real-time sepsis prediction in the ICU by machine learning methods, with tools for interpretative analysis of the predictions. In particular, we focus on the deployment of the system in a target medical center with small historical samples. METHODS: Light Gradient Boosting Machine (LightGBM) and multilayer perceptron (MLP) were trained on Medical Information Mart for Intensive Care (MIMIC-III) dataset and then finetuned on the private Historical Database of local Ruijin Hospital (HDRJH) using transfer learning technique. The Shapley Additive Explanations (SHAP) analysis was employed to characterize the feature importance in the prediction inference. Ultimately, the performance of the sepsis prediction system was further evaluated in the real-world study in the ICU of the target Ruijin Hospital. RESULTS: The datasets comprised 6891 patients from MIMIC-III, 453 from HDRJH, and 67 from Ruijin real-world data. The area under the receiver operating characteristic curves (AUCs) for LightGBM and MLP models derived from MIMIC-III were 0.98 - 0.98 and 0.95 - 0.96 respectively on MIMIC-III dataset, and, in comparison, 0.82 - 0.86 and 0.84 - 0.87 respectively on HDRJH, from 1 to 5 h preceding. After transfer learning and ensemble learning, the AUCs of the final ensemble model were enhanced to 0.94 - 0.94 on HDRJH and to 0.86 - 0.9 in the real-world study in the ICU of the target Ruijin Hospital. In addition, the SHAP analysis illustrated the importance of age, antibiotics, net balance, and ventilation for sepsis prediction, making the model interpretable. CONCLUSIONS: Our machine learning model allows accurate real-time prediction of sepsis within 5-h preceding. Transfer learning can effectively improve the feasibility to deploy the prediction model in the target cohort, and ameliorate the model performance for external validation. SHAP analysis indicates that the role of antibiotic usage and fluid management needs further investigation. We argue that our system and methodology have the potential to improve ICU management by helping medical practitioners identify at-sepsis-risk patients and prepare for timely diagnosis and intervention. TRIAL REGISTRATION: NCT05088850 (retrospectively registered).

Excellent Outcome in Living Donor Liver Transplantation: Treating Patients With Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is a fatal condition, and liver transplantation (LT) is a vital option for these patients. However, the result of living donor LT (LDLT) for ACLF is not well investigated. This study investigated the outcomes of LDLT in patients with ACLF compared with patients without ACLF. This was a single-center, retrospective, matched case-control study. From July 2002 to March 2017, a total of 112 patients with ACLF who underwent LDLT were enrolled according to the consensus of the Asian Pacific Association for the Study of the Liver. A total of 224 patients were selected for control comparison (non-ACLF) with demographic factors (sex, age, and body mass index) matched (1:2). Patients with ACLF were stratified into ACLF 1, 2, and 3 categories according to the number of organ failures based on the Chronic Liver Failure-Sequential Organ Failure Assessment score. Survival and surgical outcomes after LDLT were analyzed. The Model for End-Stage Liver Disease and Child-Turcotte-Pugh scores in the ACLF group were significantly higher than those in the non-ACLF group (P < 0.001). The 90-day, 3-year, and 5-year survival rates in the ACLF and non-ACLF groups were 97.3%, 95.5%, 92.9%, respectively, and 96.9%, 94.2%, and 91.1%, respectively (P = 0.58). There was more intraoperative blood loss in the ACLF group than in the non-ACLF group (P < 0.001). The other postoperative complications were not significantly different between the groups. A total of 20 patients (17.9%) in the ACLF group presented with 3 or more organ system dysfunctions (ACLF 3), and the 90-day, 3-year, and 5-year survival rates were comparable with those of ACLF 1 and ACLF 2 (P = 0.25). In carefully selected patients, LDLT gives excellent outcomes in patients with ACLF regardless of the number of organs involved. Comprehensive perioperative care and timely transplantation play crucial roles in saving the lives of patients with ACLF.

Statin use is associated with a lower risk of recurrence after curative resection in BCLC stage 0-A hepatocellular carcinoma.

BACKGROUND: Use of statins is associated with a reduced risk of hepatocellular carcinoma (HCC). However, the effect of statin use on HCC recurrence is unclear. This study aimed to evaluate the effect of statin use on recurrence after curative resection among patients with HCC. METHODS: We retrospectively assessed 820 patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or A HCC who underwent primary resection between January 2001 and June 2016 at Kaohsiung Chang Gung Memorial Hospital. Exposure to statins was defined as use of a statin for at least 3 months before HCC recurrence. Factors that influenced overall survival (OS) and recurrence-free survival (RFS) were analyzed using Cox proportional hazards models. RESULTS: Of the 820 patients, 46 (5.6%) used statins (statin group) and 774 (94.4%) did not (non-statin group). During the mean follow-up of 76.5 months, 440 (53.7%) patients experienced recurrence and 146 (17.8%) patients died. The cumulative incidence of HCC recurrence was significantly lower in the statin group than the non-statin group (p = 0.001); OS was not significantly different between groups. In multivariate analysis, age (hazard ratio [HR]: 1.291; p = 0.010), liver cirrhosis (HR: 1.743; p < 0.001), diabetes (HR:1.418; p = 0.001), number of tumors (HR: 1.750; p < 0.001), tumor size (HR: 1.406; p = 0.004) and vascular invasion (HR: 1.659; p < 0.001) were independent risk factors for HCC recurrence, whereas statin use (HR: 0.354; p < 0.001) and antiviral therapy (HR: 0.613; p < 0.001) significantly reduced the risk of HCC recurrence. The statin group still had lower RFS than the non-statin group after one-to-four propensity score matching. CONCLUSION: Statins may exert a chemo-preventive effect on HCC recurrence after curative resection.

Microscopic portal vein invasion is a powerful predictor of prognosis in patients with hepatocellular carcinoma who have undergone liver resection.

BACKGROUND AND OBJECTIVES: A recent study proposed simple classifications of microscopic vascular invasion (MVI): microscopic portal vein invasion (MPVI) and microvessel invasion (MI). We aim to validate these classifications of MVI. METHODS: This retrospective study consecutively enrolled 514 Barcelona Clinic Liver Cancer stage 0, A, and B naïve hepatocellular carcinoma patients who underwent liver resection in our institution from 2011 to 2017. RESULTS: Among these 514 patients, 240 patients were classified as having no MVI at all (designated as no vascular invasion, NVI), 157 patients were classified as having MI only, and 117 patients were classified as having MPVI. The 5-year overall survival (OS) rate in the MI-only group was 83.3%, which was not significantly different from that of the NVI group (87.2%), p = .20. Using NVI as a reference, multivariate analysis showed that MI-only is not an independent variable associated with OS. The 5-year OS in the MPVI group was 59.2%, which was significantly lower than those for MI-only (p < .001) and NVI groups (p < .001). Using NVI as a reference, multivariate analysis showed that MPVI is an independent variable associated with OS (HR, 3.12; 95% CI, 1.80-5.40; p < .001). CONCLUSIONS: The results of this study validate the simple MVI classifications to be clinically useful.

The Role of Protease-Activated Receptor 2 in Hepatocellular Carcinoma after Hepatectomy.

Background and Objectives: Protease activated receptor-2 (PAR2) is elevated in a variety of cancers and has been promoted as a potential therapeutic target. However, the clinical and prognostic values of PAR2 in hepatocellular carcinoma (HCC) are poorly characterized. This study aimed to evaluate the expression of PAR2 in HCC tissues and examine the prognostic value of PAR2 after resection in HCC. Materials and Methods: Two hundred and eight resected specimens were collected from HCC patients at Kaohsiung Chang Gung Memorial Hospital. PAR2 protein expression was assessed by western blotting in HCC tissues and matched normal tissues. The correlation between PAR2 expression and clinicopathological parameters was analyzed. Disease-free survival (DFS) and overall survival (OS) were compared using the log-rank test. A Cox regression model was used to identify independent prognostic factors. Results: PAR2 was expressed at higher levels in HCC tissues than the paired adjacent nontumor tissues. High expression of PAR2 was associated with advanced tumor, node, metastasis (TNM )stage and histological grade. Kaplan-Meier analysis indicated high PAR2 expression was associated with poorer DFS and OS compared to low PAR2 expression. Multivariate analyses indicated high PAR2 expression [hazard ratio (HR), 1.779, p = 0.006), α-fetoprotein (AFP) (HR, 1.696, p = 0.003), liver cirrhosis (HR, 1.735, p = 0.002), and advanced TNM stage (HR, 2.061, p < 0.001) were prognostic factors for DFS, and advanced TNM stage (HR, 2.741, p < 0.001) and histological grade (HR, 2.675, p = 0.002) and high PAR2 expression (HR, 1.832, p = 0.012) were significant risk factors for OS. In subgroup analyses, the combination of PAR2 expression and serum AFP provided improved prognostic ability for OS and DFS. Conclusion: Combination PAR2 and AFP predict HCC outcomes after resection. PAR2 represents a potentially clinically relevant biomarker for HCC.

Gratitude and Suicidal Ideation in Undergraduates in Taiwan: The Mediating Role of Self-Esteem and Meaning in Life.

This study examined both the mediation effects of self-esteem and meaning in life for the relationship between gratitude and suicidal ideation in late adolescence. A total of 276 Taiwanese university students completed measures of gratitude, self-esteem, meaning in life, and suicidal ideation. Path analyses indicated that self-esteem and meaning in life acted as full mediators of the association between gratitude and suicidal ideation. The identified model also revealed a significant path from gratitude through self-esteem and meaning in life to suicidal ideation. A multigroup analysis found that the paths did not differ by genders. Implications for future research and limitations of the present findings are discussed.

Self-Esteem and Depression as Mediators of the Effects of Gratitude on Suicidal Ideation Among Taiwanese College Students.

This study aimed at examining the roles of self-esteem and depression in the relationship between gratitude and suicidal ideation. A total of 814 Taiwanese college students ranging in age from 18 to 22 years completed measures of gratitude, self-esteem, depression, and suicidal ideation. Structural equation modeling showed partial mediation effects of self-esteem and depression between gratitude and suicidal ideation. Moreover, a multigroup analysis found that males with higher levels of self-esteem could protect themselves from depression more easily than their female counterparts. Implications for future research and limitations of the present findings are discussed.

Liver resection of hepatocellular carcinoma within and beyond the Barcelona Clinic Liver Cancer guideline recommendations: Results from a high-volume liver surgery center in East Asia.

BACKGROUND: The Barcelona Clinic Liver Cancer (BCLC) guidelines were updated in 2012, and a single large hepatocellular carcinoma (HCC) more than 5 cm was regarded as BCLC stage A rather than B in the updated version. In this study, we sought to re-evaluate the outcomes of patients with HCC who underwent liver resection (LR) within (stage 0 and A) and beyond (stage B and C) the BCLC guideline recommendations of the updated BCLC staging system. METHODS: This retrospective study enrolled 774 consecutive patients with naïve HCC who underwent LR from 2011 to 2018 at our institution. The overall survival (OS) and recurrence-free survival (RFS) of these patients were examined. RESULTS: Of the patients, 606 had BCLC stage 0 or A HCC, and 168 had BCLC stage B or C HCC. The 5-year OS and RFS among the patients within the BCLC criteria for LR were 75.2% and 56.1%, respectively, vs 54.9% and 34.0%, respectively, among the patients beyond the BCLC criteria (P < .001). Alpha-fetoprotein more than 400 ng/mL (hazard ratio = 2.06, 95% confidence interval, 1.31-3.26, P = .002) was the only independent variable associated with recurrence among the patients beyond the BCLC criteria. CONCLUSIONS: LR provided acceptable outcomes among selected patients with BCLC stage B and C HCC.

The ALBI Grade is a Good Predictive Model for Very Late Recurrence in Patients with Hepatocellular Carcinoma Undergoing Primary Resection.

BACKGROUND: Hepatocellular carcinoma (HCC) patients still have risk for very late recurrence after curative resection. This study assesses prognostic factors in HCC patients with recurrence-free survival (RFS) for 5 years after primary resection. METHODS: We enrolled 383 HCC patients who received primary tumor resection and achieved more than 5 years without recurrence after resection between January 2001 and April 2013. Predictive factors, including albumin-bilirubin (ALBI) grade, for RFS and overall survival (OS) were analyzed. RESULTS: After a median follow-up of 103 months, 57 patients (14.9%) had recurrent HCC, and 14 (3.7%) died. Independent predictors for HCC recurrence were male sex (p = 0.035), pre-operative liver cirrhosis (LC) (p = 0.025), serum creatinine > 1.5 mg/dL (p = 0.045), post-operative 5th-year alpha-fetoprotein (AFP) > 15 ng/ml (p < 0.001), LC (p = 0.004), and ALBI grades 2 and 3 (p < 0.001). I ndependent risk factors for poor survival were age >70 years (p = 0.002), post-operative 5th-year AFP > 15 ng/ml (p = 0.003), and ALBI grades 2 and 3 (p = 0.002). Patients whose deteriorated ALBI grades 5 years after resection had adverse RFS outcomes compared to those with constant (p = 0.056) and improved ALBI grades (p = 0.008). In subgroup analysis, patients with post-operative 5th-year ALBI grades 2 and 3 had significantly poorer RFS and OS (both p < 0.001) than those with grade 1 among patients with low post-operative 5th-year AFP (<15 ng/mL). CONCLUSION: In HCC patients without recurrence for 5 years after curative resection, post-operative 5th-year ALBI grade is useful for predicting outcomes, even with low AFP during follow-up.

Circulating exosomal miR-92b: Its role for cancer immunoediting and clinical value for prediction of posttransplant hepatocellular carcinoma recurrence.

A recurrence of hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) is one of the major concerns reflecting the higher mortality of HCC. This study aimed to explore the impact of circulating exosomes on HCC development and recurrence. One-shot transfusion of hepatoma serum to naïve rats induced liver cancer development with gradual elevation of alpha-fetoprotein (AFP), but exosome-free hepatoma serum failed to induce AFP elevation. The microarray analysis revealed miR-92b as one of the highly expressing microribonucleic acids in hepatoma serum exosomes. Overexpression of miR-92b enhanced the migration ability of liver cancer cell lines with active release of exosomal miR-92b. The hepatoma-derived exosomal miR-92b transferred to natural killer (NK) cells, resulting in the downregulation of CD69 and NK cell-mediated cytotoxicity. Furthermore, higher expression of miR-92b in serum exosomes was confirmed in HCC patients before LDLT, and its value at 1 month after LDLT was maintained at a higher level in the patients with posttransplant HCC recurrence. In summary, we demonstrated the impact of circulating exosomes on liver cancer development, partly through the suppression of CD69 on NK cells by hepatoma-derived exosomal miR-92b. The value of circulating exosomal miR-92b may predict the risk of posttransplant HCC recurrence.

Endoscopic injection sclerotherapy for pediatric bleeding esophageal varices complicated by gastric vein, main portal vein, splenic mesenteric junction, and splenic vein occlusion: a case report.

BACKGROUND: Endoscopic injection sclerotherapy (EIS) is a life-saving procedure for pediatric patients with bleeding gastric varices (GV) associated with advanced liver cirrhosis and severe portal hypertension. Because of the lack of an endoscopic banding ligation device for pediatric patients, EIS is usually performed for bleeding esophageal varices (EV) in infants with congenital biliary atresia. CASE PRESENTATION: We present a case of a 15-month-old female infant with type I biliary atresia with jaundice (total serum bilirubin, 22.2 mg/dL), hypoalbuminemia (serum albumin level, 2.58 g/dL), coagulopathy (prothrombin time > 20 s compared with that of a normal control), ascites, splenomegaly, portal hypertension (portal vein velocity, 3.9-5.6 cm/sec of hepatopetal flow), and repeated bleeding of the varices after receiving three doses of intravascularly administered Histoacryl 1 ampoule mixed with Lipiodol UF 8 mL in the EV. Prominent GV and EV were occluded by EIS. The sclerosing agent was also present in the main portal vein, splenic mesenteric junction, and splenic vein, causing an engorged inferior mesenteric vein. The patient underwent total hepatectomy and living donor liver transplantation (LDLT) by left lateral segment graft (segments 2, 3, and 4 of the middle hepatic vein trunk) and left portal vein graft to the recipient inferior mesenteric vein anastomosis. Portal vein stent placement via segment 4 of the portal vein stump was performed from the inferior mesenteric vein to the umbilical portion of the left portal vein. The patient is still alive and doing well after the LDLT. CONCLUSIONS: EIS is a life-saving procedure in cases involving bleeding EV complicated by gastric, main portal vein, splenic mesenteric junction, and splenic vein occlusions; hence, it should be kept in mind as a treatment for EV complications in pediatric patients.

P4 Stump Approach for Intraoperative Portal Vein Stenting in Pediatric Living Donor Liver Transplantation: An Innovative Technique for a Challenging Problem.

OBJECTIVE: The aim of this study was to evaluate the utility of the P4 stump stenting approach for treating portal vein (PV) complications in pediatric living donor liver transplantation (LDLT). BACKGROUND: PV complications cause significant morbidity and mortality in pediatric LDLT. Biliary atresia in the backdrop of pathological PV hypoplasia and sclerosis heightens the complexity of PV reconstruction. The authors developed a novel approach for intraoperative PV stenting via the graft segment 4 PV stump (P4 stump) to address this challenge. METHODS: From April 2009 to December 2016, 15 pediatric LDLT recipients (mean age 10.3 ±â€Š5.0 months, mean graft-recipient weight ratio 3.70%) underwent intraoperative stenting for suboptimal PV flow (<10 cm/s) or PV occlusion after collateral ligation and graft repositioning. Under portography, metallic stents were deployed via the reopened P4 stump of the left lateral segment grafts. RESULTS: PV diameter and peak flow increased significantly after stent placement (2.93 ±â€Š1.74 to 7.01 ±â€Š0.91 mm and 2.0 ±â€Š9.2 to 17.3 ±â€Š3.5 cm/s, respectively, P = 0.001 for both), and there were no technical failures. Stents in all surviving patients remained patent up to 8 years (mean 27.7 months), with no vascular or biliary complications. After implementation of the P4 approach, the incidence of variceal bleeding as a late complication decreased from 7% to zero. CONCLUSION: The P4 stump stenting approach affords procedural convenience, ease of manipulation, and consistent results with the potential for excellent long-term patency in children despite continued growth. This technique obviates the need for more demanding post-transplant stenting, and may become a substitute for complicated revision surgery, portosystemic shunting, or retransplantation.