No Prognostic Impact of Graft-to-Recipient Weight Ratio on Hepatocellular Carcinoma Recurrence Following Living Donor Liver Transplantation.

BACKGROUND The effects of a low graft-to-recipient weight ratio (GRWR) on the prognosis of patients with hepatocellular carcinoma (HCC) are unclear. The present study examined whether the GRWR had an impact on the rate of HCC recurrence following living donor liver transplantation (LDLT). MATERIAL AND METHODS This retrospective observational single-center study included 856 patients who underwent LDLT for HCC between January 2006 and December 2016 at Asan Medical Center and evaluated the association between GRWR and post-transplant tumor recurrence. RESULTS Of the 856 patients who underwent LDLT for HCC, 54 (6.3%), 272 (31.8%), 274 (32.0%), and 256 (29.9%) had GRWR <0.8%, 0.8-0.99%, 1.0-1.19%, and ≥1.2%, respectively. Analysis of all patients revealed that the disease-free survival (DFS; P=0.545) and overall survival (OS; P=0.313) rates were not different in these 4 groups. Subgroups analyses also showed that GRWR did not influence survival rates in patients within (DFS: P=0.398; OS: P=0.676) and beyond (DFS: P=0.602; OS: P=0.649) the Milan criteria, or in patients with alpha-fetoprotein-des-γ-carboxyprothrombin-tumor volume scores <5log (DFS: P=0.633; OS: p=0.285) and ≥5log (DFS: P=0.674; OS: P=0.906). CONCLUSIONS GRWR less than 0.8% did not demonstrate a noteworthy prognostic influence on the oncological results among patients who had undergone LDLT for HCC. High-volume multi-center studies are necessary to validate these findings.

Safety of right liver donation after improving steatosis through weight loss in living donors: a retrospective study.

BACKGROUND: Living donor liver transplantation using hepatic steatosis-improved grafts mitigates donor shortage. Herein, we aimed to evaluate the safety and feasibility of right-lobe adult-to-adult living donor liver transplantation using grafts improved through donor weight loss. METHODS: In this retrospective study conducted in a single institution in the Republic of Korea, we reviewed the medical records of living liver donors who lost ≥ 10% of their body weight to improve steatosis before right lobe donation between January 2015 and December 2020. Overall, 1040 right-lobe donors were included, with 150 and 890 donors in the weight loss and control (non-steatosis) groups, respectively. RESULTS: We performed 1:1 individual matching using the greedy matching method, by which 124 patients were included in each group. The median period from the date of the first visit to donation was 113 (interquartile range: 78-184) days in the weight loss group. As body weight changed from 82.8 ± 13.7 kg to 70.8 ± 11.8 kg (p < 0.0001), body mass index also improved from 27.8 ± 3.9 kg/m2 to 23.8 ± 3.1 kg/m2 (p < 0.0001). No significant between-group differences existed in the postoperative laboratory data for living donors and recipients. The incidence of postoperative complications in donors was comparable between the groups (control group, 9.7%; weight loss group, 13.7%; p = 0.3185). The graft and recipient survival rates were comparable between the groups (p = 1.000). CONCLUSION: Weight loss through diet and exercise significantly could improve hepatic steatosis in living donor candidates for liver transplantation, with the surgical outcomes in recipients and donors being equivalent to those in recipients and non-steatotic donors.

Dual regulation of NEMO by Nrf2 and miR-125a inhibits ferroptosis and protects liver from endoplasmic reticulum stress-induced injury.

Rationale: The surge of severe liver damage underscores the necessity for identifying new targets and therapeutic agents. Endoplasmic reticulum (ER) stress induces ferroptosis with Gα12 overexpression. NF-κB essential modulator (NEMO) is a regulator of inflammation and necroptosis. Nonetheless, the regulatory basis of NEMO de novo synthesis and its impact on hepatocyte ferroptosis need to be established. This study investigated whether Nrf2 transcriptionally induces IKBKG (the NEMO gene) for ferroptosis inhibition and, if so, how NEMO induction protects hepatocytes against ER stress-induced ferroptosis. Methods: Experiments were conducted using human liver tissues, hepatocytes, and injury models, incorporating NEMO overexpression and Gα12 gene modulations. RNA sequencing, immunoblotting, immunohistochemistry, reporter assays, and mutation analyses were done. Results: NEMO downregulation connects closely to ER and oxidative stress, worsening liver damage via hepatocyte ferroptosis. NEMO overexpression protects hepatocytes from ferroptosis by promoting glutathione peroxidase 4 (GPX4) expression. This protective role extends to oxidative and ER stress. Similar shifts occur in nuclear factor erythroid-2-related factor-2 (Nrf2) expression alongside NEMO changes. Nrf2 is newly identified as an IKBKG (NEMO gene) transactivator. Gα12 changes, apart from Nrf2, impact NEMO expression, pointing to post-transcriptional control. Gα12 reduction lowers miR-125a, an inhibitor of NEMO, while overexpression has the opposite effect. NEMO also counters ER stress, which triggers Gα12 overexpression. Gα12's significance in NEMO-dependent hepatocyte survival is confirmed via ROCK1 inhibition, a Gα12 downstream kinase, and miR-125a. The verified alterations or associations within the targeted entities are validated in human liver specimens and datasets originating from livers subjected to exposure to other injurious agents. Conclusions: Hepatic injury prompted by ER stress leads to the suppression of NEMO, thereby facilitating ferroptosis through the inhibition of GPX4. IKBKG is transactivated by Nrf2 against Gα12 overexpression responsible for the increase of miR-125a, an unprecedented NEMO inhibitor, resulting in GPX4 induction. Accordingly, the induction of NEMO mitigates ferroptotic liver injury.

Reconstruction of all hepatic arteries in right lobe grafts with 2 hepatic arteries and zero percent hepatic artery thrombosis.

Hepatic artery thrombosis (HAT) is a common cause of graft loss in living-donor liver transplantation, occurring in ~2.5%-8% of patients. Some right lobe grafts have 2 hepatic arteries (HAs), and the optimal reconstruction technique remains controversial. This study aimed to identify risk factors for HAT and to evaluate the efficacy of reconstructing 2 HAs in right lobe grafts. This retrospective, single-center study analyzed 1601 living-donor liver transplantation recipients with a right liver graft and divided them into 1 HA (n = 1524) and 2 HA (n = 77) groups. The reconstruction of all HAs was performed using a microscope with an interrupted suture. The primary outcome was any HAT event. Of the 1601 patients, 37.8% had a history of transcatheter arterial chemoembolization, and 130 underwent pretransplant hepatectomy. Extra-anatomical arterial reconstruction was performed in 38 cases (2.4%). HAT occurred in 1.2% of patients (20/1601) who underwent surgical revascularization. In the multivariate analysis, undergoing pretransplant hepatectomy ( p = 0.008), having a female donor ( p = 0.02), having a smaller graft-to-recipient weight ratio ( p = 0.002), and undergoing extra-anatomical reconstruction ( p = 0.001) were identified as risk factors for HAT. However, having 2 HA openings in right liver grafts was not a risk factor for HAT in our series. Kaplan-Meier survival analysis showed no significant difference in graft survival and patient survival rates between the 1 HA and 2 HA groups ( p = 0.09, p = 0.97). In our series, although the smaller HA in the 2 HA group should increase the risk of HAT, HAT did not occur in this group. Therefore, reconstructing both HAs when possible may be a reasonable approach in living-donor liver transplantation using a right liver graft with 2 HA openings.

Achieving 400 Living Donor Liver Transplantations Annually During the COVID-19 Pandemic: A Single-Center Experience.

BACKGROUND: The COVID-19 pandemic has had a major impact on liver transplantation (LT) and living donor programs globally. PURPOSE: In this study, we aimed to present the principles and strategies of our LT program during the pandemic period and describe its achievements. BASIC PROCEDURES: We retrospectively reviewed the outcomes of 1417 LTs performed at Asan Medical Center, Seoul, Korea, from 2020 to 2022. Of these, 216 recipients who received transplants from deceased donors were excluded, and 1201 recipients who received transplants from 1268 live donors were included in the study, including 38 children <18 years old. MAIN FINDINGS: Among the 1201 living donor LT (LDLT) recipients, the most common indication for LT was unresectable hepatocellular carcinoma (315/1163, 27.1%) in adults and biliary atresia (29/38, 76.3%) in pediatric recipients. Emergency LDLT was performed in 40 patients (3.3%). The median model of end-stage liver disease and pediatric end-stage liver disease scores were 13.9 ± 7.2 and 13.8 ± 7.1, respectively. In-hospital mortality of recipients was higher than usual at 2.2%, but the cause of death was not related to COVID-19 infection. Of the 1268 live donors who underwent hepatectomy for liver donation, 660 (52.1%) underwent hepatectomy using a minimally invasive approach. Although 17 (1.3%) live donors experienced major complications, there were no serious life-threatening complications and no mortality. CONCLUSION: Even in a pandemic era, a team with well-established infection control protocols, patient-tailored surgical strategies, and thorough perioperative care can maintain LDLT at a similar quantitative and qualitative level as in a non-pandemic era.

Reduced Ceramides Are Associated with Acute Rejection in Liver Transplant Patients and Skin Graft and Hepatocyte Transplant Mice, Reducing Tolerogenic Dendritic Cells.

We set up this study to understand the underlying mechanisms of reduced ceramides on immune cells in acute rejection (AR). The concentrations of ceramides and sphingomyelins were measured in the sera from hepatic transplant patients, skin graft mice and hepatocyte transplant mice by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Serum concentrations of C24 ceramide, C24:1 ceramide, C16:0 sphingomyelin, and C18:1 sphingomyelin were lower in liver transplantation (LT) recipients with than without AR. Comparisons with the results of LT patients with infection and cardiac transplant patients with cardiac allograft vasculopathy in humans and in mouse skin graft and hepatocyte transplant models suggested that the reduced C24 and C24:1 ceramides were specifically involved in AR. A ceramide synthase inhibitor, fumonisin B1 exacerbated allogeneic immune responses in vitro and in vivo, and reduced tolerogenic dendritic cells (tDCs), while increased P3-like plasmacytoid DCs (pDCs) in the draining lymph nodes from allogeneic skin graft mice. The results of mixed lymphocyte reactions with ceranib-2, an inhibitor of ceramidase, and C24 ceramide also support that increasing ceramide concentrations could benefit transplant recipients with AR. The results suggest increasing ceramides as novel therapeutic target for AR, where reduced ceramides were associated with the changes in DC subsets, in particular tDCs.

Modified patch-conduit venoplasty for portal vein hypoplasia in pediatric liver transplantation.

Background: Portal vein (PV) interposition can induce various PV-related complications, making more reliable techniques necessary. The present study describes the development of a modified patch venoplasty technique, combining the native PV wall and a vein homograft conduit, called modified patch-conduit venoplasty (MPCV). Methods: The surgical technique for MPCV was optimized by simulation and applied to seven pediatric patients undergoing liver transplantation (LT) for biliary atresia combined with PV hypoplasia. Results: The simulation study revealed that inserting the whole-length native PV wall as a longitudinal rectangular patch was more effective in preventing PV conduit stenosis than the conventional technique using triangular partial insertion. These findings were used to develop the MPCV technique, in which the native PV wall was converted into a long rectangular patch, acting as a backbone for PV reconstruction. A longitudinal incision on the vein conduit converted the cylindrical vein into a large vein patch. The wall of the native PV was fully preserved as the posterior wall of the PV conduit, thus preventing longitudinal redundancy and unwanted rotation of the reconstructed PV. This technique was applied to seven patients with biliary atresia undergoing living-donor and deceased-donor split LT. None of these patients has experienced PV complications for up to 12 months after transplantation. Conclusions: This newly devised MCPV technique can replace conventional PV interposition. MCPV may be a surgical option for reliable PV reconstruction using fresh or cryopreserved vein homografts during pediatric LT.

Donor sex and donor-recipient sex disparity do not affect hepatocellular carcinoma recurrence after living donor liver transplantation.

Purpose: Studies have yielded contradictory results on whether donor sex and donor-recipient sex disparity affect hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation (LDLT). The present study assessed whether donor sex or donor-recipient sex disparity affects HCC recurrence after LDLT at a high-volume center. Methods: This study included 772 HCC patients who underwent LDLT between January 2006 and December 2015 at Asan Medical Center. Patients were divided into 4 groups based on the sex of the donor and recipient: male-to-male (n = 490, 63.5%), male-to-female (n = 75, 9.7%), female-to-male (n = 170, 22.0%), and female-to-female (n = 37, 4.8%). Results: Disease-free survival (DFS; P = 0.372) and overall survival (OS; P = 0.591) did not differ significantly among the 4 groups. DFS also did not differ significantly between LDLT recipients with male and female donors (P = 0.792) or between male and female recipients (P = 0.084). After patient matching with an α-FP/des-γ-carboxy prothrombin/tumor volume score cutoff of 5logs, donor-recipient sex disparity did not significantly affect DFS (P = 0.598) or OS (P = 0.777). There were also no differences in DFS in matched LDLT recipients with male and female donors (P = 0.312) or between male and female recipients (P = 0.374). Conclusion: Neither donor sex nor donor-recipient sex disparity significantly affected posttransplant HCC recurrence.

Evolution of the technique of renoportal anastomosis for patients with complete portal venous occlusion in living donor liver transplantation: a retrospective cohort study.

BACKGROUND: This study aimed to present our surgical technique and the long-term outcomes of living donor liver transplantations with renoportal anastomosis for patients with complete portal venous occlusion. Renoportal anastomosis (RPA) is a promising technique for portal flow reconstruction during liver transplantation in patients with complete occlusion of the portal vein and extensive splanchnic vein thrombosis. However, reports demonstrating living donor liver transplantations (LDLT) with renoportal anastomosis are rarer than those demonstrating deceased donor liver transplantation. MATERIALS AND METHODS: In this single-centre retrospective cohort study, the authors analyzed the medical records of patients who underwent portal flow reconstruction via RPA with end-to-end anastomosis between the interposition graft and LRV-connected inferior vena cava (VC) cuff. The outcomes included postoperative RPA-related morbidity and patient and allograft survival for patients who underwent LDLT with RPA. RESULTS: Fifteen patients underwent LDLT with portal flow reconstruction via RPA from January 2005 to December 2019. The median follow-up period was 80.7 months (range: 27 days-195.2 months). RPA evolved from end-to-end anastomosis in 1 (6.7%) patient to end-to-side anastomoses in the next 6 (40%) patients and finally, to end-to-end anastomoses between the inferior VC cuff connected to the left renal vein and interposing vascular grafts in 8 (53.3%) patients. After standardization of the RPA technique from the eighth case in 2011, the incidence rate of RPA-related complications significantly decreased from 42.9% (3/7) to 12.5% (1/8). At the last follow-up, all 11 surviving patients had normal liver function, and 10 patients had patent anastomoses on imaging examination. CONCLUSIONS: This standardized RPA technique using an inferior VC cuff connected to the left renal vein creates a safe end-to-end RPA.

Quantitative Prediction of Posttransplant Hepatocellular Carcinoma Prognosis Using ADV Score: Validation with Korea-Nationwide Transplantation Registry Database.

OBJECTIVE: The aim of this study is to validate the prognostic impact of ADV score (α-fetoprotein [AFP]-des-γ-carboxyprothrombin [DCP]-tumor volume [TV] score) for predicting prognosis of hepatocellular carcinoma (HCC) following liver transplantation (LT). BACKGROUND: ADV score has been reported as a prognostic surrogate biomarker of HCC following LT and hepatectomy. METHODS: The study patients were 1599 LT recipients selected from the Korean Organ Transplantation Registry database. RESULTS: Deceased-donor and living-donor LTs were performed in 143 and 1456 cases, respectively. Weak correlation was present among AFP, DCP, and TV. The viable HCC group showed ADV score-dependent disease-free survival (DFS) and overall patient survival (OS) rates from 1log to 10log (p<0.001). Prognosis of complete pathological response group was comparable to that of ADV score <1log (p≥0.099). ADV score cutoff of 5log (ADV-5log) for DFS and OS was obtained through receiver operating characteristic curve analysis with area under the curve ≥0.705. Both ADV-5log and Milan criteria were independent risk factors for DFS and OS, and their prognostic impacts were comparable to each other. Combination of these two factors resulted in further prognostic stratification, showing hazard ratios for DFS and OS as 2.98 and 2.26 respectively for one risk factor and 7.92 and 8.19 respectively for two risk factors (p<0.001). ABO-incompatible recipients with ADV score ≥8log or two risk factors showed higher recurrence rates. CONCLUSIONS: This validation study revealed that ADV score is a reliable surrogate biomarker for posttransplant HCC prognosis, which can be used for selecting LT candidates and guiding risk-based posttransplant follow-up surveillance.

Favorable Prognostic Factors for Survival Outcomes of Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis After Hepatectomy.

BACKGROUND: This study aimed to investigate prognostic factors of recurrence and survival associated with hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). PATIENTS AND METHODS: This retrospective study included 161 patients with HCC with PVTT who underwent hepatectomy between January 2003 and January 2014 at the Asan Medical Center. Regression analyses were conducted to identify favorable predictive factors for overall survival (OS) and recurrence-free survival (RFS). RESULTS: The median follow-up was 15.9 months, while 1-, 3-, and 5-year OS was 65.0%, 38.4%, and 36.0%, respectively, and 1-year RFS was 25.5%. There were no significant differences in OS and RFS between the patients with portal vein invasion (Vp) 1-2 and Vp3-4 PVTT. Patients with intrahepatic recurrence had significantly better overall survival than patients with extrahepatic recurrence. Transcatheter arterial chemoembolization and radiofrequency ablation were the most effective treatments for intrahepatic metastasis, and surgery was the most effective treatment for extrahepatic metastasis. On multivariate analysis, absence of esophageal varices, maximal tumor size < 5 cm, tumor location in single lobe, and anatomical resection were favorable prognostic factors for OS and R0 resection, and absence of microvascular invasion was a favorable prognostic factor for RFS. CONCLUSION: The long-term outcome of patients with HCC with PVTT can be improved under consideration of favorable prognostic factors including absence of esophageal varices, maximal tumor size < 5 cm, tumor location in single lobe, and anatomical resection, R0 resection, and absence of microvascular invasion. In addition, recurrent HCC required aggressive management to prolong overall survival.

Efficacy and safety of adhesion barrier in living-donor liver transplantation with right liver graft to prevent delayed gastric emptying.

Delayed gastric emptying (DGE) is a common complication of liver transplantation. This study aimed to clarify the efficacy and safety of the application of an adhesion barrier for preventing DGE in living-donor liver transplantation. This retrospective study included 453 patients who underwent living-donor liver transplantation using a right lobe graft between January 2018 and August 2019, and the incidence of postoperative DGE and complications was compared between patients in whom adhesion barrier was used (n=179 patients) and those in whom adhesion barrier was not used (n=274 patients). We performed 1:1 propensity score matching between the 2 groups, and 179 patients were included in each group. DGE was defined according to the International Study Group for Pancreatic Surgery classification. The use of adhesion barrier was significantly associated with a lower overall incidence of postoperative DGE in liver transplantation (30.7 vs. 17.9%; p =0.002), including grades A (16.8 vs. 9.5%; p =0.03), B (7.3 vs. 3.4%; p =0.08), and C (6.6 vs. 5.5%; p =0.50). After propensity score matching, similar results were observed for the overall incidence of DGE (29.6 vs. 17.9%; p =0.009), including grades A (16.8 vs. 9.5%; p =0.04), B (6.7 vs. 3.4%; p =0.15), and C (6.1 vs. 5.0%; p =0.65). Univariate and multivariate analyses showed a significant correlation between the use of adhesion barrier and a low incidence of DGE. There were no statistically significant differences in postoperative complications between the 2 groups. The application of an adhesion barrier could be a safe and feasible method to reduce the incidence of postoperative DGE in living-donor liver transplantation.

Efficacy and safety of lenvatinib in patients with recurrent hepatocellular carcinoma after liver transplantation.

INTRODUCTION: Lenvatinib is approved for the treatment of patients with metastatic or recurrent hepatocellular carcinoma (HCC); however, clinical outcomes of lenvatinib therapy in patients with post-liver transplantation (LT) HCC recurrence remain unclear. We investigated the efficacy and safety of lenvatinib in patients with post-LT HCC recurrence. METHODS: This multinational, multicenter, retrospective study included 45 patients with recurrent HCC after LT who received lenvatinib at six institutions in three countries (Korea, Italy, and Hong Kong) from June 2017 to October 2021. RESULTS: At the time of lenvatinib initiation, 95.6% (n = 43) of patients had Child-Pugh A status, and 35 (77.8%) and 10 (22.2%) participants were classified as having albumin-bilirubin (ALBI) grades 1 and 2, respectively. The objective response rate was 20.0%. With a median follow-up duration of 12.9 months (95% confidence interval [CI]: 11.2-14.7), the median progression-free survival and overall survival (OS) were 7.6 (95% CI: 5.3-9.8) months, and 14.5 (95% CI: 0.8-28.2) months, respectively. Patients with ALBI grade 1 showed significantly better OS (52.3 months, [95% CI: not assessable]) than patients with ALBI grade 2 (11.1 months [95% CI: 0.0-30.4 months], p = 0.003). The most common adverse events were hypertension (n = 25, 55.6%), fatigue (n = 17, 37.8%), and anorexia (n = 14, 31.1%). CONCLUSION: Lenvatinib showed consistent efficacy and toxicity profiles in patients with post-LT HCC recurrence that were comparable to those reported from previous studies among non-LT HCC patients. The baseline ALBI grade correlated with better OS in post-LT lenvatinib-treated patients.

Incidence of superficial left hepatic vein and its usability for graft hepatic vein venoplasty in pediatric liver transplantation.

BACKGROUNDS: The anatomy of the left hepatic vein (LHV) is variable; thus, it should be considered for graft hepatic vein (GHV) venoplasty for left lateral section (LLS) and left liver grafts. This study assessed the incidence of superficial LHV (sLHV) branches according to LHV anatomy and its usability for GHV venoplasty in pediatric liver transplantation (LT). METHODS: This study consisted of three parts: (1) anatomical classification of LHV variations and the incidence of sLHV branches; (2) morphometric simulative analysis of GHV reconstruction and (3) clinical application based on LHV anatomy. RESULTS: The LHV anatomy of 248 potential LLS graft donors was classified into four types according to the number and location of GHV openings: one single opening (type 1; n = 186 [75.0%]), two large openings (type 2; n = 35 [14.1%]), one large and one small adjacent opening (type 3; n = 14 [5.6%]), and two large widely-separated openings (type 4; n = 13 [5.2%]). An sLHV branch was identified in 87 of 248 (35.1%) donor livers. Morphometric analysis of simulative GHV venoplasty with an sLHV branch increased GHV diameters by 30% in type 1 LLS grafts and 20% in type 2/3 LLS grafts. An analysis of 50 consecutive patients who underwent pediatric LT showed that the 2-year rates of GHV obstruction were 2.0% with LLS grafts and 0% with left liver grafts. CONCLUSIONS: The GHV orifice can be enlarged through LHV anatomy-based unification venoplasty. Unification venoplasty with an sLHV branch provided sufficient enlargement of the GHV orifice.

Expression Patterns of Tumor Markers in Liver Transplant Recipients Showing Complete Pathological Response of Hepatocellular Carcinoma.

Complete pathological response (CPR) is achieved with various pretransplant locoregional treatments for hepatocellular carcinoma (HCC). This study aimed to investigate pretransplant expression of HCC tumor markers in liver transplantation (LT) recipients showing CPR. For the CPR group, 166 patients were selected from a single-institution LT database. Two control groups of 332 patients without HCC and 184 patients with partial pathological response (PPR) were also selected. The model for end-stage liver disease score in the CPR group was 11.5 ± 7.7. The number of transcatheter arterial chemoembolization sessions before LT was one in 68 patients (14.0%), two in 38 patients (22.9%), and three or more in 60 patients (36.1%). A solitary non-viable tumor was identified in 120 (86.4%) of the explant livers and the largest tumor size was 2.4 ± 1.3 cm. Living-donor and deceased-donor LTs were performed in 152 (91.6%) and 14 (8.4%) patients, respectively. The median levels of α-fetoprotein (AFP) and protein induced by Vitamin K absence or antagonist-II (PIVKA-II) measured within two weeks before LT were 4.2 ng/mL and 20 mAU/mL, respectively. These tumor marker levels were comparable to those in the no-HCC control group, but much lower than those in the PPR group (p < 0.001). Receiver operating characteristic curve analysis of AFP and PIVKA-II showed no definite cutoff values for CPR in the cohort of CPR and no-HCC patients, but significant cutoffs of 6.5 ng/mL for AFP and 29 mAU/mL for PIVKA-II were obtained in the cohort of CPR and PPR patients. The 1-, 3- and 5-year HCC recurrence and overall patient survival rates of the CPR group were 5.1% and 93.3%, 7.6% and 89.6%, and 7.6% and 89.6%, respectively. These tumor recurrence rates were much lower than those in the PPR group (p < 0.001). In conclusion, the present study results suggest that normalizing AFP and PIVKA-II after locoregional treatment is indicative of CPR. However, some CPR patients showed high expression of tumor markers; thus, pretransplant values of HCC tumor markers should be interpreted with caution.

Therapeutic strategies for liver diseases based on redox control systems.

In the liver, reactive oxygen species (ROS) are constantly released during cellular metabolic processes, and excess ROS production can cause redox stress. The redox stress is both beneficial for and harmful to the survival of cells since it modulates the cellular redox control system. The redox control system is a series of cellular responses that are responsible for maintaining a balanced oxidation-reduction status. Many cellular processes including growth, proliferation, and senescence are sensitively regulated by the redox control system. Imbalance of redox induces redox stress and damages DNA, proteins, and lipids in cells, and further contributes to the pathogenesis of severe diseases and disorders like cancer. However, the cellular redox control system also utilizes redox stress-responsive pathways and increases antioxidant enzymes to aid cell survival. Therefore, a deeper understanding of the connection between the redox control system and liver disease is likely to pave the way for the future development of new therapeutic strategies. This review will examine the redox control systems in liver with responsive regulating molecules, current knowledge of the redox control system and liver disease, and suggest potential therapeutic targets for liver diseases.

Long-Term Patency of All-in-One Sleeve Patch Graft Venoplasty in 16 Patients Who Underwent Living Donor Liver Transplantation with a Right Liver Graft: A 10-Year, Single-Center, Retrospective Study.

BACKGROUND This retrospective study from a single center aimed to evaluate the long-term patency of all-in-one sleeve venoplasty (ASV) in 16 patients who underwent living donor liver transplantation (LDLT) with a right liver graft (RLG) between 2009 and 2019. ASV unifies the right hepatic vein (RHV), short hepatic vein (SHV), and middle hepatic vein (MHV) of an RLG. ASV enables wide side-to-side anastomosis to the recipient inferior vena cava (IVC). MATERIAL AND METHODS Of 2875 patients who underwent LDLT with an RLG from August 2009 to July 2019, 16 (0.5%) patients underwent ASV. We analyzed the ASV techniques applied to these patients, as well as patient long-term outcomes. RESULTS Type 1 ASV unified 1 RHV, 1 IRHV, and 1 MHV conduit (n=12 [75.0%]). Type 2 ASV unified 1 RHV, multiple IRHVs, and 1 MHV conduit (n=4 [25.0%]). All patients are currently alive, with a mean follow-up period of 70.1±41.9 months. No patient underwent retransplantation. Follow-up computed tomography showed SHV occlusion in 1 (6.3%) patient at 4 months, resulting in 1-, 3-, and 5-year SHV patency rates of 93.8% each. MHV occlusion was identified in 6 (37.5%) patients, with 1-, 3-, and 5-year MHV patency rates of 81.3%, 68.8%, and 68.8%, respectively (P=0.037). No patient underwent endovascular stenting of the SHV or MHV. Patency rates were significantly higher for SHV than MHV (P=0.037). CONCLUSIONS ASV using various vascular patches is a useful technique enabling secure reconstruction of an RLG in grafts with complex hepatic vein anatomy or recipients with poor IVC condition.

Preoperative estimation of hemi-liver volume using standard liver volume and portal vein diameter ratio in living donor liver transplantation.

Backgrounds/Aims: Although body surface area (BSA)-based standard liver volume (SLV) formulae have been used for living donor liver transplantation and hepatic resection, hemi-liver volume (HLV) is needed more frequently. HLV can be assessed using right or left portal vein diameter (RPVD or LPVD). The aim of this study was to validate the reliability of using portal vein diameter ratio (PVDR) for assessing HLV in living liver donors. Methods: This study included 92 living liver donors (59 males and 33 females) who underwent surgery between January 2020 and December 2020. Computed tomography (CT) images were used for measurements. Results: Mean age of donors was 35.5 ± 7.2 years. CT volumetry-measured total liver volume (TLV), right HLV, left HLV, and percentage of right HLV in TLV were 1,442.9 ± 314.2 mL, 931.5 ± 206.4 mL, 551.4 ± 126.5 mL, and 64.6% ± 3.6%, respectively. RPVD, LPVD, and main portal vein diameter were 12.2 ± 1.5 mm, 10.0 ± 1.3 mm, and 15.3 ± 1.7 mm, respectively (corresponding square values: 149.9 ± 36.9 mm2, 101.5 ± 25.2 mm2, and 237.2 ± 52.2 mm2, respectively). The sum of RPVD2 and LPVD2 was 251.1 ± 56.9 mm2. BSA-based SLV was 1,279.5 ± 188.7 mL (error rate: 9.1% ± 14.4%). SLV formula- and PVDR-based right HLV was 760.0 ± 130.7 mL (error rate: 16.2% ± 13.3%). Conclusions: Combining BSA-based SLV and PVDR appears to be a simple method to predict right or left HLV in living donors or split liver transplantation.

Pediatric living donor liver transplantation for biliary embryonal rhabdomyosarcoma: a case report of a case showing disease-free survival over 2 years.

Biliary rhabdomyosarcoma is a rare tumor, but it is still the most common tumor of the biliary tract in children. We report a case of a 6-year-old boy with biliary embryonal rhabdomyosarcoma and liver metastasis, which were treated with neoadjuvant and adjuvant chemotherapy combined with living donor liver transplantation (LDLT). Initial imaging studies showed a low-attenuation intraductal mass from the left hepatic duct to the intrapancreatic common bile duct with diffuse upstream dilatation of the intrahepatic duct and liver metastasis. Endoscopic biopsy revealed embryonal rhabdomyosarcoma. After tumor size reduction through neoadjuvant chemotherapy, LDLT was planned to remove the tumor completely. A left lateral section graft weighing 330 g was harvested from his 38-year-old mother and the graft-to-recipient weight ratio was 1.94%. Routine pediatric LDLT operation was performed with deep excavation of intrapancreatic distal bile duct. The explant liver showed minimal residual embryonal rhabdomyosarcoma with no lymph node metastasis. The patient recovered uneventfully from LDLT operation. Scheduled adjuvant chemotherapy was performed for 6 months. The patient is doing well without any evidence of tumor recurrence for 26 months after LDLT. In conclusion, liver transplantation could be an effective treatment for unresectable biliary rhabdomyosarcoma in children according to the location of tumor.