SOD1 inhibition enhances sorafenib efficacy in HBV-related hepatocellular carcinoma by modulating PI3K/Akt/mTOR pathway and ROS-mediated cell death.

Hepatitis B Virus (HBV) infection significantly elevates the risk of hepatocellular carcinoma (HCC), with the HBV X protein (HBx) playing a crucial role in cancer progression. Sorafenib, the primary therapy for advanced HCC, shows limited effectiveness in HBV-infected patients due to HBx-related resistance. Numerous studies have explored combination therapies to overcome this resistance. Sodium diethyldithiocarbamate (DDC), known for its anticancer effects and its inhibition of superoxide dismutase 1 (SOD1), is hypothesized to counteract sorafenib (SF) resistance in HBV-positive HCCs. Our research demonstrates that combining DDC with SF significantly reduces HBx and SOD1 expressions in HBV-positive HCC cells and human tissues. This combination therapy disrupts the PI3K/Akt/mTOR signalling pathway and promotes apoptosis by increasing reactive oxygen species (ROS) levels. These cellular changes lead to reduced tumour viability and enhanced sensitivity to SF, as evidenced by the synergistic suppression of tumour growth in xenograft models. Additionally, DDC-mediated suppression of SOD1 further enhances SF sensitivity in HBV-positive HCC cells and xenografted animals, thereby inhibiting cancer progression more effectively. These findings suggest that the DDC-SF combination could serve as a promising strategy for overcoming SF resistance in HBV-related HCC, potentially optimizing therapy outcomes.

Aborted living-donor liver transplantation in the real-world setting, lessons from 13 937 cases of Vanguard Multi-center Study of International Living Donor Liver Transplantation Group.

There are exceedingly uncommon but clearly defined situations where intraoperative abortions are inevitable in living-donor liver transplantation (LDLT). This study aimed to summarize the cases of aborted LDLT and propose a strategy to prevent abortion or minimize donor damage from both recipient and donor sides. We collected data from a total of 43 cases of aborted LDLT out of 13 937 cases from 7 high-volume hospitals in the Vanguard Multi-center Study of the International Living Donor Liver Transplantation Group and reviewed it retrospectively. Of the 43 cases, there were 24 recipient-related abortion cases and 19 donor-related cases. Recipient-related abortions included pulmonary hypertension (n = 8), hemodynamic instability (n = 6), advanced hepatocellular carcinoma (n = 5), bowel necrosis (n = 4), and severe adhesion (n = 1). Donor-related abortions included graft steatosis (n = 7), graft fibrosis (n = 5), primary biliary cholangitis (n = 3), anaphylactic shock (n = 2), and hemodynamic instability (n = 2). Total incidence of aborted LDLT was 0.31%, and there was no remarkable difference between the centers. A strategy to minimize additional donor damage by delaying the donor's laparotomy or trying to open the recipient's abdomen with a small incision should be effective in preventing some causes of aborted LDLT, such as pulmonary hypertension, advanced cancer, and severe adhesions.

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

Liver transplantation is often the only lifesaving option for acute liver failure (ALF); however, the predictors of short-term mortality (death within one year) after living donor liver transplantation (LDLT) for ALF have yet to be defined. We retrospectively collected patients ≥18 years old who underwent LDLT for ALF between 2010 and 2020 at 35 centers in Asia. Univariate and multivariate logistic regression analyses were conducted to identify the clinical variables related to short-term mortality and establish a novel scoring system. The Kaplan-Meier method was performed to explore the association between the score and overall survival. Of the 339 recipients, 46 (13.6%) died within 1 year after LDLT. Multivariate analyses revealed 4 independent risk factors for death: use of vasopressors or mechanical ventilation, the higher model for end-stage liver disease score, and a lower graft-to-recipient weight ratio. The internally validated c-statistic of the short-term mortality after transplant (SMT) score derived from these 4 variables was 0.80 (95% confidence interval: 0.74-0.87). The SMT score successfully stratified recipients into low-, intermediate-, and high-risk groups with 1-year overall survival rates of 96%, 80%, and 50%, respectively. In conclusion, our novel SMT score based on 4 predictors will guide ALF recipient and living donor selection.

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.

Proceedings of the 28th Annual Congress of the International Liver Transplantation Society.

The 2023 Joint International Congress of the International Liver Transplantation Society (ILTS), the European Liver and Intestine Transplant Association (ELITA), and the Liver Intensive Care Group of Europe (LICAGE) held in Rotterdam, the Netherlands, marked a significant recovery milestone for the liver transplant community after COVID-19. With 1159 participants and a surge in abstract submissions, the event focused on "Liver Disorders and Transplantation: Innovations and Evolving Indications." This conference report provides a comprehensive overview of the key themes discussed during the event, encompassing Hepatology, Anesthesia and Critical Care, Acute Liver Failure, Infectious Disease, Immunosuppression, Pediatric Liver Transplantation, Living Donor Liver Transplantation, Transplant Oncology, Surgical Approaches, and Machine Perfusion. The congress provided a platform for extensive discussions on a wide range of topics, reflecting the continuous advancements and collaborative efforts within the liver transplant community.

Recipient blood group does not affect hepatocellular carcinoma recurrence after living donor liver transplantation in Korea.

PURPOSE: This study assessed whether or not the ABO blood type affects the incidence of HCC recurrence after living donor liver transplantation (LDLT). METHODS: This retrospective observational study included 856 patients with hepatocellular carcinoma (HCC) who underwent LDLT between January 2006 and December 2016 at the Asan Medical Center. RESULTS: This study included 324 patients (37.9%) with blood type A, 215 (25.1%) with blood type B, 210 (24.5%) with blood type O, and 107 (12.5%) with blood type AB. ABO-incompatible LT was performed in 136 (15.9%) patients. The independent risk factors for the disease-free survival (DFS) were maximal tumor diameter, microvascular invasion, and Milan criteria. The only independent risk factor for the overall survival (OS) was microvascular invasion. The ABO blood group did not affect the DFS (P = 0.978) or OS (P = 0.261). The DFS according to the ABO blood group did not differ significantly between the ABO-compatible (p = 0.701) and ABO-incompatible LDLT recipients (p = 0.147). The DFS according to the ABO blood group did not differ significantly between patients within the Milan criteria (p = 0.934) and beyond the Milan criteria (p = 0.525). The DFS did not differ significantly between recipients with and without type A blood (p = 0.941). CONCLUSIONS: This study demonstrated that the ABO blood group system had no prognostic impact on the oncological outcomes of patients undergoing LT for HCC.

Role of extracorporeal membrane oxygenation as a salvage therapy for liver transplantation recipients in a high-volume transplant center.

Extracorporeal membrane oxygenation (ECMO) has been used sporadically in adult orthotopic liver transplantation (OLT) recipients for the treatment of acute cardiopulmonary failure. This retrospective study aimed to identify OLT patients who would benefit from ECMO support. We reviewed 109 OLT patients who received ECMO support for more than 24 h from January 2007 to December 2020. Among the enrolled patients, 15 (13.8%) experienced 18 ECMO-related complications and 12 (11.0%) experienced ECMO reapplication after weaning during the same hospitalization period. The successful weaning rates were 50.98% in patients who received ECMO support during the peritransplantation period (0-30 days from transplantation) and 51.72% in patients who received ECMO support in the post-OLT period (more than 30 days after OLT); 24 (47.1%) and 23 (39.7%) patients survived until hospital discharge, respectively. The 109 enrolled OLT recipients who received ECMO support during the perioperative period had a 1-year survival rate of 42.6%. Multivariate analyses identified the following as significant and independent risk factors for in-hospital mortality: ECMO treatment prior to 2011 ( p = 0.04), septic shock as the indication for ECMO treatment ( p = 0.001), and a total bilirubin level of ≥5.0 mg/dl ( p = 0.02). The outcomes of adult OLT recipients with ECMO treatment were acceptable in terms of weaning success and survival until hospital discharge. This study confirmed that ECMO treatment for OLT recipients with septic shock and elevated bilirubin levels might be associated with a higher in-hospital mortality and demonstrated the importance of a multidisciplinary ECMO team approach.

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.

Salvage living donor liver transplantation versus repeat liver resection for patients with recurrent hepatocellular carcinoma and Child-Pugh class A liver cirrhosis: A propensity score-matched comparison.

Following curative liver resection (LR), resectable tumor recurrence in patients with preserved liver function leads to deciding between a repeat LR and a salvage liver transplantation (LT), if a donor's liver is available. This retrospective study compared survival outcomes and recurrence pattern following salvage living donor LT (LDLT) and repeat LR in patients with recurrent hepatocellular carcinoma (HCC). We reviewed the medical records of patients who underwent repeat LR (n = 163) or LDLT (n = 84) for recurrent HCC following curative resections, between January 2005 and December 2017 at a single institution. A 1:1 propensity score matching led to 42 patients per group. Disease-specific and recurrence-free survival were significantly better in the salvage LDLT group than in the repeat LR group (p = .042; HR = 2.40; 95% CI, 0.69-6.00 and p < .001; HR = 4.23; 95% CI, 2.05-8.71, respectively). Despite significant differences in recurrence patterns between the two groups (p = .019), the patient death rates, after recurrence, were similar for both groups (p = .760). This study indicates that salvage LDLT is superior to repeat LR for treating patients with transplantable, intrahepatic HCC recurrence, even in patients with Child-Pugh class A liver cirrhosis.

Analysis of outcomes and renal recovery after adult living-donor liver transplantation among recipients with hepatorenal syndrome.

When timely access to deceased-donor livers is not feasible, living-donor liver transplantation (LDLT) is an attractive option for patients with hepatorenal syndrome (HRS). This study's primary objective was to describe outcomes after LDLT among HRS recipients, and the secondary objective was to determine predictors of poor renal recovery after LDLT. This single-center, retrospective study included 2185 LDLT recipients divided into HRS (n = 126, 5.8%) and non-HRS (n = 2059, 94.2%) groups. The study outcomes were survival and post-LT renal recovery. The HRS group had a higher death rate than the non-HRS group (17.5% vs. 8.6%, p < 0.001). In the HRS group, post-LT renal recovery occurred in 69.0%, and the death rate was significantly lower in association with HRS recovery compared with non-recovery (5.7% vs. 43.6%, p < 0.001). Multivariable analysis indicated that post-LT sepsis (p < 0.001) and non-recovery of HRS (p < 0.001) were independent negative prognostic factors for survival. Diabetes mellitus (p = 0.01), pre-LT peak serum creatinine ≥3.2 mg/dl (p = 0.002), time interval from HRS diagnosis to LDLT ≥38 days (p = 0.01), and post-LT sepsis (p = 0.03) were important negative prognostic factors for renal recovery after LDLT. In conclusion, post-LT renal recovery was important for survival, and the interval from HRS to LDLT was significantly associated with post-LT renal recovery.

Application of Proximal Splenic Vein Embolization to Interrupt Complicated Large Splenorenal Shunts in Adult Living Donor Liver Transplantation.

OBJECTIVE: The aim of the present study is to evaluate efficacy and safety of proximal splenic vein embolization (PSVE) for liver transplant recipients having complicated large splenorenal shunts (SRS). BACKGROUND: In adult living donor liver transplantation for a patient who has large splenorenal shunts (SRS), their interruption is utmost important to maintain adequate portal flow by avoidance of portal flow steal through the preexisting SRS. We effectively managed most of the recipients with surgical ligation and/or additional radiologic embolization using by intraoperative cine-portogram. However, when complete interruption is not achieved in a few recipients having complicated large SRS, it may leave a chance of lethal portal flow steal in the recipient afterward. METHODS: PSVE was performed in 13 patients between April 2014 and November 2017. We performed a retrospective analysis of preoperative images, postoperative graft and recipient outcomes, and presence of isolated portal hypertension. RESULTS: Ten patients underwent PSVE as an additional secondary method because of portal steal syndrome through the remaining SRS after surgical interruption and/or embolization, and 3 patients underwent PSVE only as a primary method of SRS interruption. In all 13 patients, portal steal on the final intraoperative cine-portogram completely disappeared after PSVE. All patients recovered with satisfactory regeneration of the partial liver graft without the reappearance of portosystemic collaterals, and there were no procedure-related complications. CONCLUSIONS: PSVE is an effective and safe procedure to secure adequate portal flow without portal steal for patients with complicated large SRS arising from multiple sites of the splenic vein or escaping to multiple terminal ends.

Early removal of drains and lines after liver transplantation to reduce the length of hospital stay and enhance recovery - A systematic review of the literature and expert panel recommendations.

BACKGROUND: The timing of removing abdominal drains, central venous catheters (CVC), and urinary catheters (UC) on post liver transplantation (LT) outcomes is not well elucidated. OBJECTIVES: To provide international expert panel recommendations and guidelines on time of drain and catheter removal as a part of an ERAS protocol to reduce the length of hospital stay and enhance recovery. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Papers considered were those reporting one or more outcomes of interest related to drainage and line removal in the setting of LT. POSPERO Protocol ID: CRD42021238349 RESULTS: On analyzing five relevant studies pertaining to drains in patients undergoing LT (four retrospectives and one prospective), the length of hospital and/or ICU stay was similar or shorter, and postoperative morbidity and mortality were lower in those without drains. No studies pertaining specifically to the time of removal of drains, CVC's, or UC's in LT were found. Studies in patients undergoing major abdominal surgery or hepatectomies recommend early removal of CVC and UC to reduce catheter-associated infections. CONCLUSIONS: Based more on expert recommendation, we propose that abdominal drains, if placed during LT, should be removed by postoperative day 5 after LT, based on quantity and fluid characteristics (Quality of Evidence; Low to Moderate | Grade of Recommendation; Strong). Larger studies are needed to more reliably determine indications for early drain and line removal in an ERAS protocol setting.

Operative and long-term oncologic outcomes of laparoscopic versus open major liver resection in patients with a high body mass index (> 25 kg/m2): a propensity score matching analysis.

BACKGROUND: With the recent rapid increase in the prevalence of obesity, the number of obese patients requiring liver resection, including laparoscopy, has increased. Accordingly, evaluating the outcome of laparoscopic liver resection in obese patients is increasingly important. This study aimed to compare the safety and feasibility of laparoscopic major liver resection (LMR) and open major liver resection (OMR) in patients with a high body mass index (BMI > 25.0 kg/m2). METHODS: We reviewed 521 patients with high BMI (> 25.0 kg/m2) who underwent major liver resection for various indications between January 2009 and November 2018 at Asan Medical Center. We performed 1:1 propensity score matching of the LMR and OMR groups, with 120 patients subsequently included in each group. RESULTS: LMR was associated with lower blood loss and shorter postoperative hospital stays (p < 0.001). Although there was no significant difference in overall complications (p = 0.080), non-liver-specific complications were observed less frequently after LMR (p = 0.025). American Society of Anesthesiologists class > II, BMI > 30 kg/m2, and malignancy were independent predictors of morbidity. In a subgroup analysis of patients with hepatocellular carcinoma, there was no significant difference between the two groups in overall survival (hazard ratio 0.225; 95% confidence interval 0.049-1.047; p = 0.057) and recurrence-free survival (hazard ratio 0.761; 95% confidence interval 0.394-1.417; p = 0.417). CONCLUSIONS: Obesity should not be considered a contraindication for major liver resection using a laparoscopic approach; however, when applying this approach for resecting malignancies in patients with a BMI > 30 kg/m2 and comorbid diseases, special attention should be paid to the possibility of complications.

Morbidity analysis of left hepatic trisectionectomy for hepatobiliary disease and live donor.

BACKGROUND: Despite remarkable advances in surgical techniques and perioperative management, left hepatic trisectionectomy (LHT) remains a challenging procedure with a somewhat high postoperative morbidity rate compared with less-extensive resections. This study aimed to analyze the short- and long-term outcomes of LHT and identify factors associated with the postoperative morbidity of this technically demanding surgical procedure. METHODS: The medical records of 53 patients who underwent LHT between June 2005 and October 2019 at a single institution were retrospectively reviewed. The independent prognostic factor of postoperative morbidity was analyzed using the logistic regression model. RESULTS: Hepatocellular carcinoma was the most common indication for surgery (n = 21), followed by hilar cholangiocarcinoma (n = 14), intrahepatic cholangiocarcinoma (n = 10), and other pathologies (including colorectal liver metastasis, hepatolithiasis, gallbladder cancer, living donor, hemangioma, and multilocular biliary cyst; n = 8). The rates of postoperative morbidities of Clavien-Dindo grade 3 or higher and 90-day mortality were 39.6% and 1.9%, respectively. The 1-, 3-, and 5-year overall survival rates were 81.1%, 61.4%, and 44.6%, respectively. Multivariate analysis revealed that preoperative jaundice [hazard ratio (HR) = 6.15, 95% confidence interval (CI): 1.57-24.17, P = 0.009] and operative time > 420 min (HR = 4.66, 95% CI: 1.27-17.17, P = 0.021) were independent predictors of postoperative morbidity. CONCLUSIONS: The in-hospital mortality of LHT surgery can be minimalized by a reliable preoperative evaluation of liver function and selection of the dominant anatomic features of right posterior sector, active and appropriate preoperative management for obstructive cholangitis and compensatory hypertrophy of the future remnant posterior sector, and the experience of the surgeon.

Clinical impact of mild to moderate pulmonary hypertension in living-donor liver transplantation.

Severe pulmonary hypertension (PHT) is a contraindication to liver transplantation (LT); however, the prognostic implication of mild to moderate PHT in living-donor LT (LDLT) is unknown. The study cohort retrospectively included 1307 patients with liver cirrhosis who underwent LDLT. PHT was defined as a mean pulmonary artery pressure (PAP) of ≥25 mmHg, measured intraoperatively just before surgery. The primary endpoint was graft failure within 1 year after LDLT, including retransplantation or death from any cause. The secondary endpoints were in-hospital adverse events. In the overall cohort, the median Model for End-stage Liver Disease-Sodium (MELD-Na) score was 19, and 100 patients (7.7%) showed PHT. During 1-year follow-up, graft failure occurred in 94 patients (7.2%). Patients with PHT had lower 1-year graft survival (86% vs. 93.4%, P = 0.005) and survival rates (87% vs. 93.6%, P = 0.011). Mean PAP was associated with a high risk of in-hospital adverse events and 1-year graft failure. Adding the mean PAP to the clinical risk model improved the risk prediction. In conclusion, mild to moderate PHT was associated with higher risks of 1-year graft failure and in-hospital events, including mortality after LDLT in patients with liver cirrhosis. Intraoperative mean PAP can help predict the early clinical outcomes after LDLT.

Safe use of right lobe living donor livers with moderate steatosis in adult-to-adult living donor liver transplantation: a retrospective study.

Hepatic steatosis (HS) beyond a certain degree can jeopardize living donor (LD) safety, particularly in right lobe (RL) donors, making it a major obstacle for donor pool expansion in adult-to-adult living donor liver transplantation (ALDLT). From July 2004 to June 2016, 58 LDs donated their RLs despite having moderate HS (30%-50% steatosis) determined by intraoperative biopsy at a single center. We performed greedy matching to compare the outcomes of the donors and recipients of this group with those of LDs with no HS. The mean left lobe (LL) HS value in the 58 cases was 20.9 ± 12.4%, which was significantly lower than the mean RL HS value (38.8 ± 6.7%, P < 0.001). The mean ratio of the remnant LL to the total liver volume was 37.8 ± 2.2. No differences were observed in the postoperative liver function and donor and recipient morbidity and mortality rates. The liver regeneration rates in recipients and donors at 1 month, 6 months, and 1 year postoperatively did not differ significantly. The patient and graft survival rates of the recipients showed no differences. The use of well-selected RL grafts with moderate steatosis does not impair graft function, recipient outcomes, or donor safety.

Long-term perioperative outcomes of pure laparoscopic liver resection versus open liver resection for hepatocellular carcinoma: a retrospective study.

BACKGROUND: Laparoscopic treatment for hepatocellular carcinoma (HCC) has increased. We retrospectively compared the perioperative and long-term oncological outcomes of laparoscopic liver resection (LLR) with those of open liver resection (OLR) for hepatocellular carcinoma (HCC) in well-matched patient groups using propensity score matching (PSM). METHODS: We reviewed medical records of patients with HCC who underwent liver resection between July 2007 and April 2016 at our center. In total, 2335 patients were included in this study and divided into LLR (n = 264) and OLR (n = 2071) groups. For group comparisons, 1:2 PSM was used with covariates of baseline characteristics, including tumor characteristics and surgical liver resection procedures. RESULTS: After PSM, there were 217 and 434 patients in the LLR and OLR groups, respectively. The LLR group had shorter hospital stays (8.9 vs. 14.8 days; P < 0.001) and lower postoperative morbidity (6.5% vs. 12.0%; P = 0.022). The 1-, 3-, and 5-year overall survival rates were 98.1%, 87.0%, and 78.6%, respectively, for the LLR group, and 98.3%, 90.8%, and 84.3%, respectively, for the OLR group (P = 0.570). The 1-, 3-, and 5-year disease-free survival rates were 81.0%, 62.0%, and 49.1%, respectively, for the LLR group, and 85.3%, 64.7%, and 56.2%, respectively, for the OLR group (P = 0.563). CONCLUSIONS: Long-term oncological outcomes were comparable between LLR and OLR for selected patients. LLR was associated with multiple benefits, even for selected patients with cirrhosis who underwent major hepatectomy. LLR for HCC performed by an experienced surgeon could be considered a safe and feasible alternative to OLR for selected patients.

Pretransplant Hepatic Malignancy Increases Risk of De Novo Malignancy after Liver Transplantation.

BACKGROUND: Hepatocellular carcinoma (HCC) recurrence and development of de novo malignancy (DNM) after liver transplantation (LT) are the major causes of late recipient death. METHODS: We analyzed the incidence of extrahepatic DNM following living donor LT according to the status of pretransplant hepatic malignancy. We selected 2,076 adult patients who underwent primary LDLT during 7 years from January 2010 to December 2016. RESULTS: The pretransplant hepatic malignancy group (n = 1,012) showed 45 cases (4.4%) of the following extrahepatic DNMs: posttransplant lymphoproliferative disease (PTLD) in 10; lung cancer in 10; stomach cancer in 6; colorectal cancer in 5; urinary bladder cancer in 3; and other cancers in 11. The pretransplant no hepatic malignancy group (n = 1,064) showed 25 cases (2.3%) of the following extrahepatic DNMs: colorectal cancer in 3; stomach cancer in 3; leukemia in 3; lung cancer in 3; PTLD in 2; prostate cancer in 2; and other cancers in 9. Incidences of extrahepatic DNM in the pretransplant hepatic malignancy and no hepatic malignancy groups were as follows: 1.1% and 0.5% at 1 year, 3.2% and 2.0% at 3 years, 4.6% and 2.5% at 5 years, and 5.4% and 2.8% at 8 years, respectively (P = 0.006). Their overall patient survival rates were as follows: 97.3% and 97.2% at 1 year, 91.6% and 95.9% at 3 years, 89.8% and 95.4% at 5 years, and 89.2% and 95.4% at 8 years, respectively (P < 0.001). Pretransplant hepatic malignancy was the only significant risk factor for posttransplant extrahepatic DNM. CONCLUSION: Our results suggest that patients who had pretransplant hepatic malignancy be followed up more strictly because they have a potential risk of primary hepatic malignancy recurrence as well as a higher risk of extrahepatic DNM than patients without pretransplant hepatic malignancy.

Prognosis of Split Liver Transplantation Compared with Whole Liver Transplantation in Adult Patients: Single-center Results under the Korean MELD Score-based Allocation Policy.

BACKGROUND: Split liver transplantation (SLT) has been occasionally performed in Korea. This study compared the incidence and prognosis of SLT with whole liver transplantation (WLT) in adult patients. METHODS: Between June 2016 and November 2019, 242 adult patients underwent a total of 256 deceased donor liver transplantation operations. SLT was performed in 7 patients (2.9%). RESULTS: The mean age of SLT donors was 29.7 ± 7.4 years, and the mean age of recipients was 55.7 ± 10.6 years, with the latter having a mean model for end-stage liver disease score of 34.6 ± 3.1. Mean split right liver graft weight was 1,228.6 ± 149.7 g and mean graft-recipient weight ratio was 1.97 ± 0.39. Of the seven SLT recipients, Korean Network for Organ Sharing (KONOS) status was one in status 1, one in status 2 and five in status 3. The graft (P = 0.72) and patient (P = 0.84) survival rates were comparable in the SLT and WLT groups. Following propensity score matching, graft (P = 0.61) and patient (P = 0.91) survival rates remained comparable in the two groups. Univariate analysis showed that pretransplant ventilator support and renal replacement therapy were significantly associated with patient survival, whereas KONOS status category and primary liver diseases were not. Multivariate analysis showed that pretransplant ventilator support was an independent risk factor for patient survival. CONCLUSION: Survival outcomes were similar in adult SLT and WLT recipients, probably due to selection of high-quality grafts and low-risk recipients. Prudent selection of donors and adult recipients for SLT may expand the liver graft pool for pediatric patients without affecting outcomes in adults undergoing SLT.

Sequential transcatheter arterial chemoembolization and portal vein embolization before right hemihepatectomy in patients with hepatocellular carcinoma.

BACKGROUND: Recent studies showed that sequential selective transcatheter arterial chemoembolization (TACE) and portal vein embolization (PVE) provided better future liver remnant (FLR) regeneration rate and disease-free survival following surgery compared with PVE alone. The present study aimed to clarify whether preoperative sequential TACE and PVE before right hemihepatectomy can reduce postoperative hepatocellular carcinoma (HCC) recurrence and improve long-term disease-free and overall survival. METHODS: Recurrence and survival outcomes were retrospectively evaluated in 205 patients with HCC who underwent right hemihepatectomy by a single surgeon from November 1993 to November 2017. Patients were divided into four groups according to the procedure performed before the surgery: sequential TACE and PVE (TACE-PVE), PVE-only, TACE-only, or naïve control groups. The baseline patient and tumor characteristics, postoperative outcomes, recurrence-free survival and overall survival were analyzed. RESULTS: Baseline patient and tumor characteristics upon diagnosis were similar in all four groups, while sequential TACE and PVE were well tolerated. The TACE-PVE group had a higher mean increase in percentage FLR volume compared with that of the PVE-only group (17.46% ± 6.63% vs. 12.14% ± 5.93%; P = 0.001). The TACE-PVE group had significantly better overall and disease-free survival rates compared with the other groups (both P < 0.001). CONCLUSIONS: Sequential TACE and PVE prior to surgery can be an effective therapeutic strategy for patients with HCC scheduled for major hepatic resection. The active application of preoperative sequential TACE and PVE for HCC would allow more patients with marginal FLR volume to become candidates for major hepatic resection by promoting compensatory FLR hypertrophy without the deterioration of basal hepatic functional reserve or tumor progression.