International Multicenter Study of Ultra-Low GRWR Grafts in Adult Living Donor Liver Transplantation.

Decreasing the graft size in living donor liver transplantation (LDLT) increases the risk of early allograft dysfunction. Graft-to-recipient-weight-ratio (GRWR) of 0.8 is considered the threshold. There is evidence that smaller volume grafts may also provide equally good outcomes, the cut-off of which remains unknown. In this retrospective multi-center study, 92 adult LDLT with a final GRWR<=0.6 performed at 12 international liver transplant (LT) centers over a 3-year period were included. Perioperative data including preoperative status, portal flow hemodynamics (PFH) and portal flow modulation (PFM), development of SFSS, morbidity and mortality was collated and analyzed. Thirty-two (36.7%) patients developed SFSS and this was associated with increased 30-day, 90-day and one-year mortality. Pre-operative MELD and inpatient status were independent predictors for SFSS (p<0.05). Pre-LT renal dysfunction was an independent predictor of survival (Hazard ratio- 3.1;95% ci 1.1,8.9, p=0.035). PFH or PFM were not predictive of SFSS or survival. We report the largest ever multi-center study of LDLT outcomes using ultralow-GRWR grafts and for the first-time validate the ILTS-iLDLT-LTSI consensus definition and grading of SFSS. Pre-operative recipient condition rather than GRWR and PFH were independent predictors of SFSS. Algorithms to predict SFSS and LT outcomes should incorporate recipient factors along with GRWR.

TEMPORARY REMOVAL: A novel scoring system to predict short-term mortality after living donor liver transplantation for acute liver failure.

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Biliary complications after adult-to-adult living-donor liver transplantation: An international multicenter study of 3633 cases.

In living-donor liver transplantation, biliary complications including bile leaks and biliary anastomotic strictures remain significant challenges, with incidences varying across different centers. This multicentric retrospective study (2016-2020) included 3633 adult patients from 18 centers and aimed to identify risk factors for these biliary complications and their impact on patient survival. Incidences of bile leaks and biliary strictures were 11.4% and 20.6%, respectively. Key risk factors for bile leaks included multiple bile duct anastomoses (odds ratio, [OR] 1.8), Roux-en-Y hepaticojejunostomy (OR, 1.4), and a history of major abdominal surgery (OR, 1.4). For biliary anastomotic strictures, risk factors were ABO incompatibility (OR, 1.4), blood loss >1 L (OR, 1.4), and previous abdominal surgery (OR, 1.7). Patients experiencing biliary complications had extended hospital stays, increased incidence of major complications, and higher comprehensive complication index scores. The impact on graft survival became evident after accounting for immortal time bias using time-dependent covariate survival analysis. Bile leaks and biliary anastomotic strictures were associated with adjusted hazard ratios of 1.7 and 1.8 for graft survival, respectively. The study underscores the importance of minimizing these risks through careful donor selection and preoperative planning, as biliary complications significantly affect graft survival, despite the availability of effective treatments.

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.

Conductive Lanthanide Metal-Organic Frameworks with Exceptionally High Stability.

Electrically conductive metal-organic frameworks (MOFs) have been extensively studied for their potential uses in energy-related technologies and sensors. However, achieving that goal requires MOFs to be highly stable and maintain their conductivity under practical operating conditions with varying solution environments and temperatures. Herein, we have designed and synthesized a new series of {[Ln4(µ4-O)(µ3-OH)3(INA)3(GA)3](CF3SO3)(H2O)6}n (denoted as Ln4-MOFs, Ln = Gd, Tm, and Lu, INA = isonicotinic acid, GA = glycolic acid) single crystals, where electrons are found to transport along the π-π stacked aromatic carbon rings in the crystals. The Ln4-MOFs show remarkable stability, with minimal changes in conductivity under varying solution pH (1-12), temperature (373 K), and electric field as high as 800 000 V/m. This stability is achieved through the formation of strong coordination bonds between high-valent Ln(III) ions and rigid carboxylic linkers as well as hydrogen bonds that enhance the robustness of the electron transport path. The demonstrated lanthanide MOFs pave the way for the design of stable and conductive MOFs.

Novel Benchmark for Adult-to-Adult Living-donor Liver Transplantation: Integrating Eastern and Western Experiences.

OBJECTIVE: To define benchmark values for adult-to-adult living-donor liver transplantation (LDLT). BACKGROUND: LDLT utilizes living-donor hemiliver grafts to expand the donor pool and reduce waitlist mortality. Although references have been established for donor hepatectomy, no such information exists for recipients to enable conclusive quality and comparative assessments. METHODS: Patients undergoing LDLT were analyzed in 15 high-volume centers (≥10 cases/year) from 3 continents over 5 years (2016-2020), with a minimum follow-up of 1 year. Benchmark criteria included a Model for End-stage Liver Disease ≤20, no portal vein thrombosis, no previous major abdominal surgery, no renal replacement therapy, no acute liver failure, and no intensive care unit admission. Benchmark cutoffs were derived from the 75th percentile of all centers' medians. RESULTS: Of 3636 patients, 1864 (51%) qualified as benchmark cases. Benchmark cutoffs, including posttransplant dialysis (≤4%), primary nonfunction (≤0.9%), nonanastomotic strictures (≤0.2%), graft loss (≤7.7%), and redo-liver transplantation (LT) (≤3.6%), at 1-year were below the deceased donor LT benchmarks. Bile leak (≤12.4%), hepatic artery thrombosis (≤5.1%), and Comprehensive Complication Index (CCI ® ) (≤56) were above the deceased donor LT benchmarks, whereas mortality (≤9.1%) was comparable. The right hemiliver graft, compared with the left, was associated with a lower CCI ® score (34 vs 21, P < 0.001). Preservation of the middle hepatic vein with the right hemiliver graft had no impact neither on the recipient nor on the donor outcome. Asian centers outperformed other centers with CCI ® score (21 vs 47, P < 0.001), graft loss (3.0% vs 6.5%, P = 0.002), and redo-LT rates (1.0% vs 2.5%, P = 0.029). In contrast, non-benchmark low-volume centers displayed inferior outcomes, such as bile leak (15.2%), hepatic artery thrombosis (15.2%), or redo-LT (6.5%). CONCLUSIONS: Benchmark LDLT offers a valuable alternative to reduce waitlist mortality. Exchange of expertise, public awareness, and centralization policy are, however, mandatory to achieve benchmark outcomes worldwide.

Uranyl Polyoxotungstate Cluster for Visible-Light-Driven Heterogeneous C-H Selective Fluorination.

The selective fluorination of C-H bonds at room temperature using heterogeneous visible-light catalysts is both interesting and challenging. Herein, we present the heterogeneous sandwich-type structure uranyl-polyoxotungstate cluster Na17{Na@[(SbW9O33)2(UO2)6(PO3OH)6]}·46H2O (denoted as U6P6) to regulate the selective fluorination of the C-H bond under visible light and room temperature. This is the first report in which uranyl participates in the fluorination reaction in the form of an insoluble substance. U6P6 is capable of the effective selective fluorination of cycloalkanes and the recyclability of the photocatalyst due to the synergistic effect of multiple uranyl (UO2)2+ and the insolubility of organic reagents of polyoxotungstate. In situ electron paramagnetic resonance spectroscopy captured the generation of cycloalkane radicals during the photoreaction, confirming the mechanism of direct hydrogen atom transfer.

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.

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.

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.

Emerging Roles of Calcium Signaling in the Development of Non-Alcoholic Fatty Liver Disease.

The liver plays a central role in energy metabolism. Dysregulated hepatic lipid metabolism is a major cause of non-alcoholic fatty liver disease (NAFLD), a chronic liver disorder closely linked to obesity and insulin resistance. NAFLD is rapidly emerging as a global health problem with currently no approved therapy. While early stages of NAFLD are often considered benign, the disease can progress to an advanced stage that involves chronic inflammation, with increased risk for developing end-stage disease including fibrosis and liver cancer. Hence, there is an urgent need to identify potential pharmacological targets. Ca2+ is an essential signaling molecule involved in a myriad of cellular processes. Intracellular Ca2+ is intricately compartmentalized, and the Ca2+ flow is tightly controlled by a network of Ca2+ transport and buffering proteins. Impaired Ca2+ signaling is strongly associated with endoplasmic reticulum stress, mitochondrial dysfunction and autophagic defects, all of which are etiological factors of NAFLD. In this review, we describe the recent advances that underscore the critical role of dysregulated Ca2+ homeostasis in lipid metabolic abnormalities and discuss the feasibility of targeting Ca2+ signaling as a potential therapeutic approach.

Noncontrast Magnetic Resonance Angiography Clinical Application in Pre-Liver Transplant Recipients With Impaired Renal Function.

Image evaluation of the vascular architecture is essential before living donor liver transplantation (LDLT). However, the use of contrast-enhanced study in recipients with impaired renal function is limited due to the risk of acute kidney injury and nephrogenic systemic fibrosis. Therefore, a contrast medium-free method is both valuable and necessary for preoperative vascular evaluation. Recent literature reported inflow-sensitive inversion recovery (IFIR) magnetic resonance angiography (MRA) without the use of a contrast medium to be a reproducible and noninvasive tool to assess hepatic vasculature with adequate-to-good image quality. The purpose of this study is to clinically apply IFIR MRA preoperatively in LDLT recipients. We retrospectively reviewed 31 LDLT recipients with renal function impairment from March 2013 to August 2018 who received IFIR MRA as a pretransplant vascular architecture evaluation and who underwent a subsequent LDLT. The image findings were assessed for subjective image quality and were compared with intraoperative findings. Our results showed that the pretransplant vascular anatomy was well correlated with intraoperative findings in all recipients. Successful ratings with image quality scores ≥2 for proper hepatic arteries (PHAs), portal veins, and inferior vena cavas (IVCs) were 100.0%, 96.8%, and 93.5%, respectively. Readable ratings with imaging quality score ≥1 for left and right hepatic arteries and gastroepiploic arteries were 83.9%, 96.7%, and 22.6%, respectively. We also found that recipients with higher Model for End-Stage Liver Disease scores (>23) had lower image quality scores for PHAs (P = 0.003) and IVCs (P = 0.046). However, images were still satisfactory for pre-liver transplantation (LT) vascular evaluation. In conclusion, in pre-LT recipients with impaired renal function, IFIR MRA is a feasible and reproducible image modality.

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.

Transarterial Chemoembolization Using 100-µm Drug-Eluting Microspheres in Patients with Hepatocellular Carcinoma: A Prospective Study and Midterm Follow-up.

PURPOSE: The purpose of this study was to assess the safety and efficacy of drug-eluting embolic (DEE) transarterial chemoembolization for hepatocellular carcinoma (HCC) in patients who are ineligible for curative treatment, using doxorubicin-loaded Tandem (Varian Medical) microspheres. MATERIALS AND METHODS: Between October 2015 and December 2017, 98 patients with unresectable HCC (69 males, 29 females; mean age, 60.5 ± 10.0 years of age; and American Joint Committee on Cancer [AJCC] stage ≦T3a) treated with DEE transarterial chemoembolization using 100-µm doxorubicin-loaded microspheres were enrolled prospectively. All studies were reviewed and approved by the Institutional Review Board of Chang Gung Memorial Hospital. Dynamic contrast-enhanced computed tomography or magnetic resonance imaging 1 month after treatment was used for tumor response assessment according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Outcomes included overall survival (OS), progression-free survival (PFS), and downstaging profile. RESULTS: Median follow-up was 21.2 months. At follow-up examinations at 0.5-, 1-, 1.5- and 2.5-year follow-up, OS rates were 93.8%, 89.5%, 79.4%, and 77.0%, respectively. Complete response (CR), partial response, stable disease, and progressive disease were noted in 50 (51.0%), 23 (23.5%), 18 (18.4%), and 7 (7.1%) patients, respectively, with 93.9% disease control rate and 74.5% objective response rate. Mean OS was 28.7 months, and mean PFS was 19.6 months. Number of nodules >3, bilobar disease, larger tumor, and higher AJCC stage correlated with worse CR. No serious adverse events occurred after DEE transarterial chemoembolization. Successful downstage rate was 73.3% (22 of 30) and number of nodules predicting successful downstaging was 7 nodules (cutoff). CONCLUSIONS: Tandem DEE transarterial chemoembolization provides safe and effective treatment for HCC and a bridge or downstage therapy for liver transplantation.

Quantification of Functional MR Predicts Early Response in Post-doxorubicin Drug-Eluting Beads Chemoembolization for Hepatocellular Carcinoma.

BACKGROUND: The purpose of this study was to assess the value of functional MRI (fMRI) of post-doxorubicin drug-eluting beads transcatheter arterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC) as an early imaging biomarker of response to therapy. METHODS: This prospective analysis included 21 consecutive patients undergoing fMRI before and after DEB-TACE at a single medical center from January 2013 to December 2014. Functional MRI, including relative changes in apparent diffusion coefficient (ADC) and choline levels measured at hydrogen-1 magnetic resonance spectroscopy (MRS) of treated lesions, was recorded at baseline before DEB-TACE, and at 1, 2, and 4 weeks after DEB-TACE therapy. Assessment of tumor response was based on dynamic contrast-enhanced computer tomography imaging response according to modified response evaluation criteria in solid tumors. RESULTS: At post-therapy, 76% (n = 16) of patients demonstrated objective tumor response, 10% (n = 2) had stable disease, and 3 (14%) had progressive disease. Stable disease and progressive disease were designated as non-response. At week 2, the mean change in ADC value of responsive tumors was 0.35 ± 0.24 mm2/s, which was greater than that of non-response tumors (mean 0.01 ± 0.13 × 10-3 mm2/s) (P = 0.006). Significant differences were found in mean choline/water ratio between responsive (7.8 ± 4.9 × 10-3) and non-responsive (17.2 ± 4.9 × 10-3) tumors (P = 0.005). Composite scores of choline/water ratio and relative change of ADC showed significantly better diagnostic accuracy in non-responsive tumors than responsive tumors (area under the curve = 1.0; P < 0.001). CONCLUSIONS: Combined DWI and MRS may be used as an early imaging biomarker of therapy response in HCC patients after chemoembolization therapy.

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.

Optimizing biliary outcomes in living donor liver transplantation: Evolution towards standardization in a high-volume center.

Biliary complications have always been a dreaded cause of morbidity after living donor liver transplantation. While intrinsic variations in both graft and recipient biliary anatomy remain a significant factor to the difficulty of biliary reconstruction, our institution has taken advantage of its high volume of cases to critically review and evaluate modifiable operative risk factors, in particular, our surgical protocols. We present herein, the evolution of our reconstructive biliary technique from conventional methods to our current standard of microsurgical biliary reconstruction for both graft and recipient ducts. Over this period of transition, our center has created a classification system for biliary reconstruction that decreased the biliary complication rates from 40.0% to 10.2%.

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.