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Abstract 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.

Progressive familial intrahepatic cholestasis (PFIC) is an autosomal recessive inherited disease requiring liver transplantation (LT). Hepatocellular carcinoma (HCC) is very rare in infants. We present a case of living donor LT using a left lateral section graft performed in a 7-month-old female infant diagnosed with PFIC type II and HCC. No mutation on ABCB11 gene was identified. Because of progressive deterioration of liver function, living donor LT with her mother’s left lateral section graft was performed. Pretransplant serum alpha-fetoprotein (AFP) level was increased to 2,740 ng/mL, but HCC was not taken into account because of its rarity. The explant liver showed micronodular liver cirrhosis, multiple infantile hemangiomas and two HCCs of 0.7 cm and 0.3 cm in size. The patient recovered uneventfully from the LT operation. This patient has been regularly followed up with abdomen ultrasonography and AFP measurement every 6 months. The patient has been continually doing well for 8 years after the LT. In conclusion, LT is currently the only effective treatment for PFIC-associated end-stage liver diseases. HCC can develop at the cirrhotic liver of any cause, thus elevation of HCC tumor markers in pediatric patients is an important clue to perform further investigation before LT.

Background : The outcomes of liver transplantation (LT) have improved, but actual 20-year survival data have rarely been presented. Methods : Longitudinal follow-up data of 20-year LT survivors were retrospectively analyzed. The LT database of our institution was searched to identify patients who underwent primary LT from January 2000 to December 2001. The study cohort of 251 patients was divided into three groups: 207 adults who underwent living donor LT (LDLT), 22 adults who underwent deceased donor LT (DDLT), and 22 pediatric patients who underwent LT. Results : Hepatitis B virus–associated liver cirrhosis and biliary atresia were the most common indications for adult and pediatric LT, respectively. Seven patients required retransplantation, including six who underwent DDLT and one who underwent LDLT. Twenty-two patients died within 3 months after LT and 69 died at later intervals. The overall survival rates at 1, 3, 5, 10, and 20 years were 86.4%, 79.6%, 77.7%, 72.8%, and 62.6%, respectively, in the adult LDLT group; 86.4%, 72.7%, 72.7%, 72.7%, and 68.2%, respectively, in the adult DDLT group; and 86.4%, 86.4%, 81.8%, 81.8%, and 77.3%, respectively, in the pediatric LT group (P=0.545). Common immunosuppressive regimens at 20 years included tacrolimus monotherapy, tacrolimus–mycophenolate dual therapy, cyclosporine monotherapy, and mycophenolate monotherapy. Conclusions: The present study is the first report of actual 20-year survival data from a Korean high-volume LT center. The graft and patient survival outcomes reflected the early experiences of LT in our institution, with long-term outcomes being similar regardless of graft type and patient age.

Hepatic artery thrombosis (HAT) following living donor liver transplantation (LDLT) is a lethal complication. We present the case of a patient who underwent salvage redo hepatic artery reconstruction using an aorto-hepatic jump graft because of HAT following LDLT. A 64-year-old female patient diagnosed with hepatitis C virus-associated liver cirrhosis and hepatocellular carcinoma underwent salvage LDLT using a modified right liver graft. Partial graft infarct was identified at posttransplant day 4, and by day 9, it had spread. Celiac arteriography showed complete occlusion of the graft hepatic artery. We performed redo hepatic artery reconstruction using a fresh iliofemoral artery homograft 10 days after the LDLT operation because such a vessel homograft was available at our institutional tissue bank. The infrarenal aorta was dissected and an iliofemoral artery graft was anastomosed. Soon after hepatic artery revascularization, liver function progressively improved, and the infarct area at the liver graft was reduced. The patient has been doing well for 10 years without any vascular complications. In conclusion, our experience with this case suggests that salvage redo hepatic artery reconstruction using an aorto-hepatic jump graft is a feasible option to treat HAT following LDLT, as in deceased donor liver transplantation.

Background: Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CCA) has wide histologic diversity. This study investigated the prognostic impacts of cHCC-CCA histology according to the 2019 World Health Organization (WHO) classification. Methods: This retrospective observational study included 153 patients who underwent surgical resection for cHCC-CCA at Asan Medical Center between August 2012 and July 2019. Results: During the study period, 153 patients, 112 (73.2%) men and 41 (26.8%) women with a mean age of 56.4 ± 10.8 years, underwent R0 resection for cHCC-CCA. Mean tumor diameter was 4.2 ± 2.6 cm, and 147 (96.1%) patients had solitary tumors. According to 2019 WHO classification, 111 (72.5%) patients had cHCC-CCA alone, and 29 of them (26.1%) showed stem cell features. cHCC-CCA-intermediate cell carcinoma and cHCC-CCA-cholangiolocellular carcinoma were identified in 27 (17.6%) and 15 (9.8%), respectively. The 1-, 3-, and 5-year tumor recurrence and patient survival rates were 31.8% and 92.1%, 49.8% and 70.9%, and 59.0% and 61.7%, respectively. Univariate analyses revealed that significant prognostic factors were tumor size >5 cm, microscopic and macroscopic vascular invasion, lymph node metastasis, 8th American Joint Committee on Cancer (AJCC) tumor stage, and status of stem cell features. Multivariate analysis revealed 8th AJCC tumor stage and status of stem cell features as independent prognostic factors. 2019 WHO classification was not associated with post-resection prognosis. Conclusions: 2019 WHO classification was not associated with post-resection prognosis, thus was considered as simplified histologic classification requiring prognostic validation. We suggest that stem cell features should be included as an essential component of the pathology report for cHCC-CCA.

The anatomy of middle hepatic vein (MHV) varies widely, and some individuals have aberrant MHV anatomy, thus there is risk of iatrogenic damage to graft MHV during liver splitting. We present the clinical sequences of an adult recipient who received a split right liver graft with erroneous deprivation of the MHV trunk. This is the case was a 58-year-old male patient with hepatitis B virus-associated liver cirrhosis who suffered from hepatic encephalopathy. The split right liver graft had a graft-to-recipient weight ratio of 2.1%. Soon after graft reperfusion, large-sized hepatic venous congestion (HVC) appeared at the graft liver surface, indicating lack of MHV drainage. The amount of HVC was approximately 20% of the right liver graft mass at day 1, which had gradually reduced on follow-up computed tomography (CT) scans. Although liver function recovered progressively, the patient remained bed-ridden because of pre-existing hypoxic brain damage. The patient passed away 4 years after transplantation because of pneumonia and multi-organ failure. The present case implies that there is some possibility of unrecognized damage to the graft MHV during liver splitting, suggesting the necessity of preoperative donor abdomen CT scan and preparation of intraoperative ultrasonography for easy evaluation of graft liver MHV anatomy.

We have preferentially used the right gastroepiploic artery (RGEA) as an alternative for the recipient hepatic artery (HA) inflow during living donor liver transplantation (LDLT), but it was not always available. We herein present a case of adult LDLT with HA reconstruction using a greater saphenous vein (GSV) conduit because of the absence of the RGEA due to prior subtotal gastrectomy. A 55-year-old male patient diagnosed with hepatitis B virus-associated liver cirrhosis and secondary biliary cirrhosis underwent LDLT using a modified right liver graft. The upper abdominal cavity was heavily adhered due to prior abdominal surgeries, thus we had to sacrifice the common bile duct and the right HA completely. A 6-cm-long GSV segment was harvested from the left ankle and interposed between the recipient gastroduodenal artery and the graft HA. The patient recovered from LDLT and HA complications did not occur. However, 8 years after LDLT, chronic rejection occurred, thus repeated deceased donor liver transplantation was performed. This patient has been doing well for 2 years after retransplantation. In conclusion, we suggest that interposition of an autologous GSV conduit can be an alternative for establishing HA inflow in LDLT when other inflow source is not available.

Background : Some young adults have a long survival period with native liver after Kasai portoenterostomy (KPE) for biliary atresia (BA). However, a considerable proportion of these patients require liver transplantation (LT). This study aimed to analyze the indications and outcomes of LT in young adults after a long survival period with native liver after KPE. Methods : We selected seven patients who were 18 years or older at the time of LT out of 116 BA patients who underwent primary LT from 2008 to 2019 at Asan Medical Center. Results : The mean ages at KPE and LT were 2.1±0.9 months and 22.0±5.1 years, respectively. Mean serum total bilirubin level and model for end-stage liver disease score at LT were 7.91±7.22 mg/dL and 15.3±6.0, respectively. The main reasons for LT were liver cirrhosis with portal hypertension-associated complications in five patients and intractable cholangitis in two patients. There were five cases of living donor LT and two cases of deceased donor LT. All the seven patients are currently alive during the mean follow-up period of 74.7±40.9 months. One patient suffered from outflow graft vein obstruction requiring endovascular stenting. Another patient showed core antibody-positivity-induced de novo hepatitis B virus infection, which was well managed with antiviral therapy. Conclusions: Young adult patients with BA are a unique group of patients requiring specialist care regarding transition from pediatric to adult services. The outcomes of LT in young adult BA patients were excellent. Therefore, LT should be considered in patients showing serious BA-associated complications.

Background : Living liver donation by minors is regarded as justifiable only if minors possess the capacity to consent to donation and the procedure is in their best interests. This study analyzed the incidence of and reasons for living donor liver transplantation (LDLT) by minor donors in Korea, and discussed ethical issues regarding liver donation by minors. Methods : The databases of the Korean Network for Organ Sharing (KONOS) and Asan Medical Center (AMC) from 2010 to 2019 were retrospectively reviewed to determine the incidence of LDLT by minor donors. Results : From 2010 to 2019, 590 (4.1%) of 14,243 liver donors in the KONOS database and 276 (7.5%) of 3,401 liver donors in the AMC database were minors. The proportions of minor donors in the KONOS and AMC databases were highest in 2012, at 4.1% and 12.6%, respectively, and lowest in 2019, at 1.1% and 3.0%, respectively. Because most LDLT recipients had relatively low model for end-stage liver disease scores and hepatocellular carcinoma, they were unlikely candidates for deceased-donor liver transplantation and were highly likely to drop out of LDLT if they waited for 1–2 years. The donor-recipient relationship of minor donors in the AMC database was first-degree in 256 (92.8%) and second- or third-degree in 20 (7.2%). Conclusions: Liver donation by minors is limitedly acceptable only when the minor proves informed, well‐considered, and autonomous consent to the procedure and the procedure is in the minor's best interests. We suggest that minors be allowed to donate only to first-degree family members.

Salvage liver transplantation (LT) is a definite treatment for recurrent hepatocellular carcinoma (HCC) after hepatectomy. Combined hepatocellular carcinoma-cholangio-carcinoma (cHCC-CC) is not eligibly indicated for LT because of high post-transplant recurrence. We present a case of salvage living donor liver transplantation (LDLT) in a patient with tumor recurrence after surgical resection of cHCC-CC. A 61-year-old male patient diagnosed with chronic hepatitis B underwent right posterior sectionectomy for HCC. The pathological diagnosis revealed presence of a 3.2-cm-sized cHCC-CC with stem cell features and intermediate cell-subtype. Intrahepatic tumor recurrence occurred 9 months later and transarterial chemoembolization was performed. Due to the progress of recurrent tumors, ABO-incompatible LDLT was performed. The explant liver pathology revealed four small masses of cHCC-CC with stem cell features. Pulmonary metastasectomy and chest wall resection were performed for metastatic lesions at 10 months after LT. Multiple tumor recurrence was detected at 21 months after LT with progression despite sorafenib administration. Currently, the patient is alive for past 26 months after LT. In conclusion, the clinical sequences of this case suggest that the role of salvage LT for cHCC-CC is much more limited than that for HCC because the tumor biology of cHCC-CC is more aggressive compared with HCC.

Background : Liver transplantation (LT) for foreign patients is a sensitive issue because of possibility of transplant tourism and difficulty in posttransplant follow-up. This study describes the institutional standard framework and experience of living donor LT (LDLT) for overseas non-Korean patients in a Korean high-volume LDLT center. Methods : The framework and experience of LDLT for 105 non-Korean patients from 2010 to 2019 were retrospectively investigated. Results : Only 3.1% of patients who underwent LDLT were overseas non-Koreans; of these, 83.8% were from the United Arab Emirates and Mongolia. Selection criteria for recipients and donors were the same as for Korean citizens. Of the 105 recipients, 95 (90.5%) were adults. The most common reasons for transplantation were hepatitis B or C virus-associated liver cirrhosis. Of the 95 adults, 78 (82.1%) received right liver grafts, and 16 (16.8%) received dual grafts. The most frequent donors for adult recipients were sons and daughters, whereas the most frequent donors for pediatric recipients were parents. Of the 10 pediatric patients, eight were from the United Arab Emirates; their common primary diseases were biliary atresia, acute liver failure, hepatoblastoma, and genetic metabolic diseases. The 1-, 3-, and 5-year posttransplant overall patient survival rates in all patients were 96.2%, 92.4%, and 92.4%, respectively. The 5-year overall patient survival rates were 91.8% in adult recipients and 100% in pediatric recipients (P=0.47). Conclusions: LDLT at Korean high-volume LT centers including our institution is safe and effective for non-Korean patients with end-stage liver disease seeking alternatives not available in their own countries.

Background : Favorable outcomes achieved after deceased donor liver transplantation (DDLT) suggest that use of elderly donors may be an effective way to expand donor pool. Methods : This was a retrospective analysis of adult DDLT using elderly donors. It was a double-arm study that compared posttransplant outcomes to ascertain whether use of elderly donors (aged ≥76 years) has adverse effects on outcome of DDLT. Elderly donor study group included 14 donors aged ≥76 years and elderly donor control group comprised 39 donors aged 66–75 years. Results : Mean donor age of the study and control groups was 78.2±3.1 years and 68.9±2.7 years, respectively (P

Background : Epithelioid hemangioendothelioma (EHE) is a rare borderline vascular tumor. Due to its rarity and protean behavior, the optimal treatment of hepatic EHE has not yet been standardized. This single-center study describes outcomes in patients with hepatic EHE who underwent living donor liver transplantation (LDLT). Methods : The medical records of patients who underwent LDLT for hepatic EHE from 2007 to 2016 were reviewed. Results : During 10-year period, four patients, one man and three women, of mean age 41.3±11.1 years, underwent LDLT for hepatic EHE. Based on imaging modalities, these patients were preoperatively diagnosed with EHE or hepatocellular carcinoma, with percutaneous liver biopsy confirming that all four had hepatic EHE. The tumors were multiple and scattered over entire liver, precluding liver resection. Blood tumor markers were not elevated, except that CA19-9 and des-γ-carboxy prothrombin was slightly elevated in one patient. Mean model for end-stage liver disease score was 10.8±5.7. All patients underwent LDLT using modified right liver grafts, with graft-recipient weight ratio of 1.11±0.19, and all recovered uneventfully after LDLT. One patient died due to tumor recurrence at 9 months, whereas the other three have done well without tumor recurrence, resulting in 5-year disease-free and overall patient survival rates of 75% each. The patient with tumor recurrence was classified as a high-risk patient based on the original and modified hepatic EHE-LT scoring systems. Conclusions: LDLT can be an effective treatment for patients with unresectable hepatic EHEs that are confined within the liver and absence of macrovascular invasion and lymph node metastasis.

Interest in utilizing organs from non–heart-beating donors (NHBDs) has increased because of the organ shortage. However, liver transplantation (LT) from NHBDs has been scarcely performed in Korea because only Maastricht category IV is legally permitted. We present one case of LT from an NHBD with extracorporeal membrane oxygenation (ECMO) support. The case was a 42-year-old male patient with alcoholic liver cirrhosis. The model for end-stage liver disease score was 28. The donor was a 47-year-old female who was diagnosed with brain death due to cerebral infarct, but cardiac arrest occurred before brain death was finally confirmed. Thus, venous-arterial type ECMO was initiated for circulatory support. In the operating room, asystole developed just after ECMO was stopped. After waiting for 5 minutes, cardiac death was declared. It took 6 minutes from skin incision to aorta perfusion. The recipient hepatectomy and graft implantation were performed according to the standard procedures of adult whole LT. The patient recovered from LT uneventfully and has been doing well for 9 years after LT. The use of NHBDs is a method to increase the potential pool of organ donors, thus changes toward enhanced public awareness and acceptance of donating organs, and legal support at the government level are necessary.

Introduction: There is no consensus regarding selection criteria on liver transplantation (LT) for hepatocellular carcinoma (HCC), especially for living donor liver transplantation, although emerging evidence has been found for the effectiveness of bridging or downstaging. Objective: We evaluated the long-term outcomes of patients who underwent LT with or without bridging or downstaging for HCC. Methods: This retrospective study included 896 LT recipients with HCC between June 2005 and May 2015. Recurrence-free survival (RFS), overall survival (OS), and their associated factors were evaluated. Results: The 5-year RFS in the full cohort of 896 patients was 82.4%, and the OS was 85.3%. In patients with initial Organ Procurement and Transplantation Network (OPTN) T1 and T2, the 5-year RFS and OS did not significantly differ between LT groups with and without bridging (all p ≥ 0.05). The 5-year RFS and OS of OPTN T3 patients with successful downstaging were not significantly different from those of patients with OPTN T2 with primary LT (p = 0.070 and p = 0.185), but were significantly higher than in patients with OPTN T3 with downstaging failure and initial OPTN T1 or T2 with progression (all p < 0.001). In the multivariate analysis, last alpha-fetoprotein before LT ≥70 ng/mL (hazard ratio [HR]: 1.77, p = 0.001; HR: 1.72, p = 0.004), pretransplant HCC status exceeding the Milan criteria (HR: 5.12, p < 0.001; HR: 3.31, p < 0.001), and positron emission tomography positivity (HR: 2.57, p < 0.001; HR: 2.57, p < 0.001) were independent predictors for worse RFS and OS. Conclusions: The impact of bridging therapy on survival outcomes is limited in patients with early-stage HCC, whereas OPTN T1 or T2 with progression provides worse prognosis. OPTN T3 should undergo LT after successful downstaging, and OPTN T3 with successful downstaging allows for acceptable long-term posttransplant outcomes.

We present a case of successful split liver transplantation (LT) using a hyperreduced left lateral segment (LLS) graft in a 106-day-old female infant patient weighing 4 kg. The patient was diagnosed with progressive familial intrahepatic cholestasis. Her general condition and liver function deteriorated progressively and she was finally allocated for a split LT under status 1. The deceased donor was a 20-year-old female weighing 63.7 kg. We performed in situ liver splitting and in situ size reduction sequentially. The weight of the hyperreduced LLS graft was 225 g, with a graft-recipient weight ratio of 5.5%. We performed recipient hepatectomy and graft implantation according to the standard procedures for pediatric living-donor LT. Since the graft was too large for primary abdomen closure, the abdominal wall was closed in three stages to make a prosthetic silo, temporary closure with a xenograft sheet, and final primary repair over 2 weeks. The patient has been doing well for more than 6 years after transplantation. In conclusion, split LT using a hyperreduced LLS graft can be a useful option for treating small infants. However, large-for-size graft-related problems, particularly in terms of graft thickness, still remain to be solved.

Background : The present study intended to investigate the allocation status of pediatric deceased donor liver allografts. We analyzed the incidence of pediatric deceased donors in the Korean Network for Organ Sharing (KONOS) database and single-institutional status of liver transplantation (LT) using pediatric donors. Methods : We assessed the nationwide incidence of pediatric donors aged ≤15 years and conducted single-center analysis of LT using pediatric donors. Results : Between 2010 and 2019, pediatric donors aged ≤15 years accounted for 171 out of 4,395 donors (3.9%) in the KONOS database and 31 out of 640 liver donors (4.8%) in Asan Medical Center (AMC) database. In AMC, 11 (35.5%) and 20 (64.5%) grafts were allocated to pediatric recipients aged ≤15 years and adult recipients aged ≥19 years, respectively. All nine livers from donors aged ≤5 years were implanted in pediatric recipients aged ≤5 years. From 21 donors aged ≥9 years, 16 whole liver grafts and four split extended right liver grafts were implanted in 20 adult recipients and two split left lateral section grafts were implanted in two pediatric recipients. Four split liver grafts were implanted in other institutions. The overall patient survival rates at 1, 3, and 5 years were 90.9%, 80.8%, and 80.8%, respectively in pediatric-to-pediatric LT group and 69.6%, 58.4%, and 58.4%, respectively in pediatric-to-adult LT group (P=0.21). Conclusions: More than half of the pediatric donor livers were allocated to adult patients. Recipient criteria for allocation of liver allografts from pediatric donors need revision for children on pediatric LT waitlist.

Background : Living donor liver transplantation (LDLT) causes bleeding in recipients during the careful preservation of most perihilar structures during this surgery. This case-control study aimed to analyze the effect of prolonged hepatic inflow occlusion (PHIO) when applied during recipient hepatectomy in LDLT. Methods : The study group comprised patients who underwent PHIO with Model for End-Stage Liver Disease (MELD) scores ranging from 26 to 35 (n=20). The following two control groups were selected according to their MELD scores: the low-MELD score group (MELD scores of 15-20, n=40) and the high-MELD score group (MELD scores of 26-35, n=40). Total dissection time for hepatic mobilization and dissection and blood loss during these procedures were compared between the two groups. Results : In the PHIO study group, mean total dissection time and mean PHIO duration were 226.3±59.4 and 68.2±19.1 minutes, respectively. Twelve patients underwent PHIO twice, and the other eight patients underwent PHIO once. The low-MELD score control group and the PHIO study group showed similar dissection duration (216.0±43.9 vs. 226.3±59.4 minutes, P=0.82) and similar blood loss volume during dissection (2,112.5±1,614.9 vs. 2,350.0±951.9 mL, P=0.17). The high-MELD score control group and the PHIO study group showed similar dissection duration (241.0±41.9 vs. 226.3±59.4 minutes, P=0.71), but the PHIO group showed a significantly lower blood loss during dissection than the high-MELD score group (2,350.0±951.9 vs. 2,815.0±1,813.9 mL, P=0.002). During and after PHIO, no adverse complication was observed, except for transient splanchnic congestion. Conclusions: Our findings suggest that PHIO is a simple effective method to reduce intraoperative bleeding during hepatic mobilization and dissection during LDLT operation requiring difficult dissection.

Background : Homologous vein allografts are adequate for reconstruction of the middle hepatic vein (MHV) in living-donor liver transplantation (LDLT). However, supply is a matter of concern. To replace homologous vein allografts, polytetrafluoroethylene (PTFE) grafts were used. This study aimed to assess the long-term patency rates and complications of PTFE grafts used for MHV reconstruction of LDLT in a high-volume liver transplantation center. Methods : We analyzed the patency rates of PTFE-interposed MHV in 100 LDLT recipients and reviewed complications including PTFE graft migration. Results : The mean age was 53.5±5.4 years and male to female ratio was 73:27. Primary diagnoses were hepatitis B virus infection (n=71) and other (n=28). Mean model for endstage liver disease score was 16.2±8.3. V5 reconstruction was performed as either single anastomosis (n=85) or double anastomoses (n=14). No V5 reconstruction was required in one patient. V8 reconstruction was performed as single anastomosis, double anastomoses, and no reconstruction in 75, 0, and 25 patients, respectively. During a mean follow-up of 6 years, three recipients required early MHV stenting within 2 weeks. After 3 months, there were no episodes of congestion-associated infarct, regardless of MHV patency. Patency rates of PTFE-interposed MHV were 54.0%, 37.0%, and 37.0% at 1, 3, and 5 years, respectively. Unwanted PTFE graft migration occurred in two recipients, and the actual incidence was 2% at 5 years. Conclusions: PTFE grafts combined with small-artery patches demonstrated acceptably high short- and long-term patency rates. Since the risk of unwanted migration of PTFE graft is not negligibly low, lifelong surveillance is necessary to detect unexpected rare complications.

Background : To understand the changing demands and recent trends in the indications for living donor liver transplantation (LDLT), the present study aimed to analyze the indications for LDLT performed in a high-volume transplantation center over 10 years. Methods : The liver transplantation database at our institution was searched to identify patients who underwent LDLT during a 10-year period from January 2008 to December 2017. The study subjects (n=3,145) were divided into two groups: adult patients (n=3,019, 92.7%) and pediatric patients (n=126, 3.9%). Results : In the adult recipients, the primary diagnoses were hepatitis B virus (HBV)- associated liver cirrhosis (n=1,898, 62.9%), alcoholic liver disease (n=482, 16.0%), hepatitis C virus-associated cirrhosis (n=203, 6.7%), acute liver failure (n=127, n=4.2%), and other diseases (n=157, 5.2%). The mean Model for End-Stage Liver Disease score was 15.6±8.8 (range, 6-40). The proportion of patients with HBV-associated liver disease gradually decreased, but the proportion of those with alcoholic liver disease increased. Hepatocellular carcinoma (HCC) was diagnosed in 1,467 patients (48.6%). The mean proportion of patients with HCC was 63.1% among those with HBVassociated liver disease. In pediatric recipients, the primary diagnoses were biliary atresia (n=51, 40.5%), liver failure of various causes (n=37, 29.4%), metabolic disease (n=22, 17.5%), hepatoblastoma (n=12, 9.5%), and infectious diseases (n=4, 3.2%). Conclusions: Our results showed that there were some significant changes in the indications of LDLT. We believe that our results may reflect the real changes in the indications of LDLT and they will be useful for predicting further changes in the future.

Background : The mammalian target of the rapamycin inhibitor has dual inhibitory effects on cell growth and angiogenesis. This study aimed to analyze the usage of everolimus on actual immunosuppression (IS) regimens through a cross-sectional study in a high-volume liver transplantation (LT) center. Methods : Our institutional LT database was searched for adult patients who underwent primary LT surgery between January 2010 and December 2016. We identified 2,093 LT recipients with observation periods of 1 to 8 years.Results : We divided the 2,093 recipients into three groups according to the posttransplant follow-up period as follows: group A (12-36 months; n=680), group B (37-60 months; n=560), and group C (>60 months; n=853). The individual IS agents were tacrolimus in 1,807 patients (86.3%), cyclosporine in 169 patients (8.1%), mycophenolate mofetil (MMF) in 1,310 patients (62.6%), and everolimus in 115 patients (5.5%). The most common IS regimens were tacrolimus-MMF combination and tacrolimus monotherapy, regardless of the posttransplant period. Patients with pretransplant malignancies were administered everolimus more frequently than those without pretransplant malignancies (P

Background : The Korean model for end-stage liver disease (MELD) score-based liver allocation system was started in June 2016 in Korea.Methods : This study analyzed the detailed allocation results of deceased donor liver transplantation (DDLT) during the first 2 years after the MELD score-based liver allocation system implementation at a high-volume liver transplantation (LT) center in Korea.Results : This study included 174 patients with age above 12 years. The patient ABO blood groups were A (n=65, 37.4%), B (n=51, 29.3%), O (n=28, 16.1%), and AB (n=30, 17.2%). The LT types were primary LT in 141 patients (81.0%) and retransplantation in 33 (19.0%). The Korean Network for Organ Sharing status categories at LT were as follows: status 1 (n=11, 6.3%), status 2 (n=82, 47.1%), status 3 (n=63, 36.2%), and status 4 (n=18, 10.3%). The mean MELD score at LT and waiting period were 36.6±4.6 and 62.1±98.2 days in blood group A; 37.6±3.6 and 25.7±38.1 days in blood group B; 38.8±2.7 and 26.0±30.5 days in blood group O; and 34.8±5.5 and 68.4±110.5 days in blood group AB (P

Background : Autologous portal vein Y-graft (PYG) interposition has been the standard procedure for reconstruction of double portal vein (PV) orifices of right liver grafts during living donor liver transplantations. However, it has the disadvantage of being vulnerable to anastomotic stenosis. A refined technique of conjoined unification venoplasty (CUV) was developed to secure PV reconstruction. Methods : We reviewed the surgical outcomes in PV reconstructions using CUVs in 21 cases which were followed up for >3 years. Results : The mean age of recipients was 51.7±4.9 years. The model for end-stage liver disease score was 15.3±6.4. The graft-recipient weight ratio was 1.12±0.21. Recipient PYGs were harvested in all cases. All living donors were blood relatives or relatives through marriage with type III PV anomalies. The number of right liver graft PV orifices was two in 19 cases and three in two cases. For the central intervening vein patch, a PV segment was used in six cases, and an autologous greater saphenous vein patch was used in the remaining 15 cases. The 21 patient cohort displayed a 100% 4-year patient survival rate. None of them underwent any PV interventions including interventional stenting. Serial follow-up computed tomography scans revealed that the reconstructed PV showed early reshaping with a stable streamlined configuration for over 3 years.Conclusion : s: PV reconstruction using the CUV technique appears to be significantly more effective in preventing PV complications. We believe that CUV is a useful technique to reconstruct right liver grafts with multiple PV orifices.

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.

Intracranial hemorrhage (ICH) following liver transplantation is a potentially devastating complication. Although hypertension and thrombocytopenia are well-known risk factors for ICH in the general population, their roles in ICH after liver transplantation have not been well established. ICH occurred in two patients with alcoholic cirrhosis after deceased donor liver transplantation. A 38-year-old man presented with acute ICH in the right parietal lobe on day 16 after transplantation, with decreased level of consciousness and seizure. His mental status improved with immediate neurological treatment without surgery. In the second case, a 42-year-old woman had acute ICH in the left frontoparietal lobes on day 9 after transplantation, with generalized tonic-clonic seizures. Urgent cerebral decompression was performed. The patient’s neurological symptoms gradually recovered. In both cases, the blood platelet count was less than 50,000/mm3. Monitoring cerebral pressure for ICH is an invasive and challenging method, especially in patients with cirrhosis who have issues with hemostasis. Surgeons should be critically mindful of the risk of rapid neurological deterioration in patients with cirrhosis. Careful neurologic examination and immediate treatment to lower intracranial pressure for ICH after liver transplantation in patients with alcoholic cirrhosis are very important.

Hepatic intrasinusoidal (HI) natural killer (NK) cells from liver perfusate have unique features that are similar to those of liver-resident NK cells. Previously, we have reported that HI CD56bright NK cells effectively degranulate against SNU398 hepatocellular carcinoma (HCC) cells. Thus, the aim of this study was to further investigate the phenotype and function of HI NK cells. We found that HI CD56bright NK cells degranulated much less to Huh7 cells. HI CD56bright NK cells expressed NKG2D, NKp46, TNF-related apoptosis-inducing ligand (TRAIL), and FAS ligand (FASL) at higher levels than CD56dim cells. SNU398 cells expressed more NKG2D ligands and FAS and less PD-L1 than Huh7 cells. Blockade of NKG2D, TRAIL, and FASL significantly reduced the cytotoxicity of HI NK cells against SNU398 cells, but blockade of PD-L1 did not lead to any significant change. However, HI NK cells produced IFN-γ well in response to Huh7 cells. In conclusion, the cytotoxicity of HI CD56bright NK cells was attributed to the expression of NKG2D, TRAIL, and FASL. The results suggest the possible use of HI NK cells for cancer immunotherapy and prescreening of HCC cells to help identify the most effective NK cell therapy recipients.

Major resection of cirrhotic livers can result in hepatic failure, but no supportive treatment has been found to be generally effective. We successfully treated a 63-year-old woman with post-hepatectomy liver failure with plasmapheresis. Following right hepatectomy, the initial postoperative recovery of liver function was favorable, except for ascites. One month later, however, the amount of drained ascites increased up to 2 l/day. In addition, serum cholesterol concentration gradually decreased to around 30 mg/dl, and serum total bilirubin rose to 11.1 mg/dl. Plasmapheresis was performed, and after just 2 sessions, serum cholesterol level was rapidly corrected and prothrombin time was restored. After 3 sessions of plasmapheresis, the usual rebound rise of serum bilirubin disappeared, and the amount of ascites drained also decreased slowly. The patient underwent a total of 5 sessions of plasmapheresis over 2 weeks, after which liver function improved slowly, and she was finally discharged 72 days after liver resection. Mild ascites requiring diuretic therapy persisted over 3 months. She is doing well to date 10 months after liver resection without tumor recurrence or hepatic decompensation. This limited experience suggests that plasmapheresis can be a useful liver support for post-hepatectomy liver failure.

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. [ABSTRACT FROM AUTHOR]