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Background and Objectives Mesenchymal stem cells (MSCs) elicit therapeutic effects against liver fibrosis in animal models. Human liver stem cells (HLSCs) are cells isolated from human liver tissue that have mesenchymal morphology and express MSC markers. HLSCs also possess intrahepatic stem cell properties. We introduce a rat model of liver fibrosis and trans-portal transplantation of HLSC to demonstrate alleviation of liver fibrosis. Methods and Results Liver fibrosis was induced by intraperitoneal injection of Carbon tetrachloride (CCl4). Sprague Dawley rats underwent simultaneous partial hepatectomy of the left hepatic lobe and HLSC transplantation via the portal vein. Gross appearance of the liver observed following CCl4 injection showed cholestasis and surface nodularity. Sirius red staining revealed deposition of collagen fibers in the extracellular matrix (ECM). Following HLSC transplantation, human albumin secreting cells were detected by immunohistochemistry in liver specimens. Quantitative measurements of fibrosis area stained by Sirius red were compared between baseline and post-HLSC transplant (1×107 cells) following 10 weeks of CCl4 treatment liver specimens. Fibrosis area (p

BACKGROUND The number of pediatric patients awaiting liver transplantation has decreased. Due to its increased use in Korea, split liver transplantation (SLT) may be a substitute for living donor liver transplantation (LDLT); however, the outcomes of pediatric SLT and LDLT in Korea remain unreported. MATERIAL AND METHODS We reviewed data of Korean patients aged18 years who received SLT from 2005 to 2014, based on the Korea national database and compared to recipients who underwent LDLTs at Seoul National University Hospital during the same period. RESULTS A total of 63 and 56 patients were included in SLT and LDLT, respectively. The most common indication for LT was biliary atresia (60.3% in SLT vs 67.9% in LDLT). The Pediatric End-Stage Liver Disease score did not differ between the groups (P0.05). The 1-, 3-, and 5-year overall survival rates were 92.1%, 90.2%, and 86.6% in the SLT and 96.4%, 94.6%, and 94.6% in the LDLT groups, respectively (P=0.21); the corresponding graft survival rates were 88.9%, 87.1%, and 83.6% in the SLT and 92.9%, 91.0%, and 91.0% in the LDLT groups, respectively (P=0.31). Fulminant hepatic failure was a risk factor for graft failure [OR, 8.77 (1.08-70.92); P=0.042], but not overall survival [OR, 11.78 (0.56-247.29); P=0.11]. CONCLUSIONS The graft and overall survival rates of SLT and LDLT were not different in pediatric patients in Korea, and fulminant hepatic failure was the only risk factor affecting graft survival outcomes.

Background Solid pseudopapillary tumors (SPTs) are rare, but they comprise the majority of pediatric pancreatic neoplasms. However, studies on these conditions in pediatric patients are lacking. The aim of this study was to investigate the clinical characteristics and treatment outcomes in children and adolescents with SPTs. Methods This retrospective study included 51 patients with SPTs who had undergone pancreatic tumor resection before the age of 19 years at Samsung Medical Center in Korea (from November 1994 to August 2020). We investigated the postoperative outcomes. Results Of the 51 patients with SPTs (female, 88.2%), the median age at diagnosis was 14 years (range, 8–19). The most common symptom was abdominal pain (60.8%), and 14 patients (27.5%) were asymptomatic. The median maximal tumor diameter was 7 cm (range, 1.4–14), and the pancreatic body and/or tail were involved in 68.6% of patients. The short-term complication rate was 21.5%, and the recurrence rate was 5.9%. New-onset diabetes mellitus (NODM) occurred in four patients. Conclusions The ideal treatment for SPTs is complete resection of the tumor; however, long-term postoperative complications including NODM should be monitored carefully, particularly in children and adolescents.

This study analyzed factors related to allograft fibrosis in clinically stable pediatric liver transplantation patients. Pediatric patients who underwent liver transplantation from January 1997 to January 2008 and further underwent 10-year protocol biopsies were examined. Grades of inflammation and fibrosis were classified based on Banff criteria and the Liver Allograft Scoring (LAF) system, respectively. Risk factors for fibrosis were analyzed using logistic regression. Sixty-six patients with no clinical signs of chronic liver disease were included. Forty-one patients out of 66 (62.1%) had certain stage of allograft fibrosis. More than five events with aminotransferase >50 U/L was a risk factor for a LAF score 1–2 portal fibrosis (OR = 3.156, CI 1.059–9.410, P = 0.039). More than five events with aminotransferase >100 U/L was a risk factor for LAF score 2 portal fibrosis (OR = 13.978, CI 2.025–97.460, P = 0.007) and LAF score 1–2 sinusoidal fibrosis (OR = 4.897, CI 1.167–20.548, P = 0.030). Positive autoantibody (OR = 3.298, CI 1.039–10.473, P = 0.043) and gamma-glutamyl transferase 60 U/L (OR = 6.201, CI 1.096–35.097, P = 0.039) were related to sinusoidal fibrosis with LAF score of 1–2 and 2, respectively. Experience of post-transplantation lymphoproliferative disease was related to LAF score 1–2 portal fibrosis (OR = 7.371, CI 1.320–41,170, P = 0.023) and LAF score 1–2 centrolobular fibrosis (OR = 8.822, CI = 1.378–56.455, P = 0.022). Our results indicate that liver fibrosis is common in patients with no clinical signs of graft deterioration and repeated elevation of aminotransferases, positive autoantibodies, elevated gamma-glutamyl transferase and experience of post-transplantation lymphoproliferative disease are suspicious signs for fibrosis.

Background Generic tacrolimus (Tacrobell®) is commonly used in liver transplant patients in Korea. No previous studies have assessed the long-term efficacy and safety of generic tacrolimus for adult deceased donor liver transplantation (DDLT) patients. The aim of the present study was to evaluate the long-term efficacy and safety of generic tacrolimus compared to brand-name tacrolimus (Prograf®) in adult DDLT recipients. Methods Two hundred sixty-five adult DDLTs were performed in our center between 2003 and 2017. To determine the efficacy and safety of generic tacrolimus, renal function (estimated glomerular filtration rate [eGFR] and creatinine), infectious complications, rejection-free survival rates, and patient survival rates were investigated. Results Of 265 patients, 193 were selected and divided into a generic tacrolimus group (n=147) and a brand-name group (n=46). Mean follow-up duration was 63.2 ± 44.3 months. The 1-year, 3-year, 5-year, and 10-year patient survival rates were 89.1%, 86.9%, 84.5%, and 75.2%, respectively, in the generic tacrolimus group and 95.7%, 88.9%, 86.3%, and 83.7% in the brand-name tacrolimus group. There were no statistically significant differences in the infectious complications, new-onset diabetes, and renal dysfunction included mean serum creatinine level or eGFR after DDLT between the two groups. Increased recipient age, continuous renal replacement therapy (CRRT) in the pre-transplant phase, and acute rejection were predisposing factors for patient death. Conclusion The present study shows that generic tacrolimus is an alternative comparable to brand-name tacrolimus in adult DDLT patients.

The innovative pure laparoscopic living donor right hepatectomy (LLDRH) procedure for liver transplantation has never been fully compared to open living donor right hepatectomy (OLDRH). We aimed to compare the donor safety and graft results of pure LLDRH to those of OLDRH.From May 2013 to July 2017, 288 consecutive donors underwent either OLDRH (n = 197) or pure LLDRH (n = 91). After propensity score matching, 72 donors were included in each group. The primary outcome was postoperative complications during a 90-day follow-up period. Comprehensive complication index, duration of hospital stay, need for additional pain control, readmission, and donor outcomes were also compared.The incidence of major complication during the 90-day follow-up was higher in the LLDRH group than the OLDRH group (6.6% vs 15.4%, P = 0.017) but was not statistically significant in propensity-matched analysis (11.1% vs 13.9%, odds ratio [OR], 1.29; 95% confidence interval [CI], 0.47-3.51; P = 0.62). A right hepatic duct1 cm was independently associated with complication in the pure LLDRH group (odds ratio, 4.01; 95% confidence interval, 1.08-14.99; P = 0.04).In the initial 91 pure LLDRH cases, incidence of major complication was higher than in the OLDRH group, but the difference was not significant in propensity-matched analysis. A right hepatic duct verified as1 cm may be related to increased frequency of complications in pure LLDRH donors. Further analysis is needed.

Pediatric liver transplantation has evolved into an effective treatment for a variety of liver diseases in the pediatric population. Over the past 25 years, pediatric liver transplantation results in Korea have matched international standards, and Korea has become one of the most important leaders in living donor liver transplantation. This review presents the cumulative outcomes of pediatric liver transplants in Korea and highlights other concerns related to pediatric liver transplantation, particularly pediatric liver allocation policy and split liver transplantation.

Background and Objectives Mesenchymal stem cells (MSCs) elicit therapeutic effects against liver fibrosis in animal models. Human liver stem cells (HLSCs) are cells isolated from human liver tissue that have mesenchymal morphology and express MSC markers. HLSCs also possess intrahepatic stem cell properties. We introduce a rat model of liver fibrosis and trans-portal transplantation of HLSC to demonstrate alleviation of liver fibrosis. Methods and Results Liver fibrosis was induced by intraperitoneal injection of Carbon tetrachloride (CCl4). Sprague Dawley rats underwent simultaneous partial hepatectomy of the left hepatic lobe and HLSC transplantation via the portal vein. Gross appearance of the liver observed following CCl4 injection showed cholestasis and surface nodularity. Sirius red staining revealed deposition of collagen fibers in the extracellular matrix (ECM). Following HLSC transplantation, human albumin secreting cells were detected by immunohistochemistry in liver specimens. Quantitative measurements of fibrosis area stained by Sirius red were compared between baseline and post-HLSC transplant (1×107 cells) following 10 weeks of CCl4 treatment liver specimens. Fibrosis area (p

PurposePheochromocytoma (PCC) and paraganglioma (PGL) (PPGL) are rare neuroendocrine tumors, and data on managing these conditions in children and adolescents are lacking. The objective of this study was to demonstrate the clinical presentation and treatment outcomes in children and adolescents with PPGL in a single tertiary care center in Korea.MethodsThis retrospective study included 23 patients diagnosed with PCC (n = 14) and PGL (n = 9) before the age of 21 at Samsung Medical Center (from June 1994 to June 2019). We describe age, gender, family history, clinical characteristics, laboratory findings, pathologic findings, therapeutic approaches, and treatment outcomes.ResultsOf the 23 patients, 14 had PCC and nine had PGL. The median age at diagnosis was 16.8 years (range, 6.8–20.8 years). The common presenting symptoms were hypertension (n = 10), headache (n = 9), palpitation (n = 4), and sweating (n = 4). The plasma or 24-hour urine catecholamine and/or metabolite concentrations were markedly elevated in 22 patients with PPGL, but were normal in one patient with carotid body PGL. All tumors were visualized on computed tomography. Genetic tests were performed in 15 patients, and seven patients showed mutations in RET (n = 3), SDHB (n = 3), and VHL (n = 1). All patients underwent surgery, and complete excision was performed successfully. Three patients with metastasis underwent postoperative adjuvant therapy.ConclusionThis study suggests that pediatric PPGL tends to be extra-adrenal and bilateral and shows a higher potential for genetic mutations. Considering the hereditary predisposition of pediatric PPGL, genetic screening tests are strongly recommended, and lifelong follow-up is needed to detect recurrence and metastasis. Further research with a larger sample size and routine genetic screening is needed to better understand the genetic conditions and long-term prognosis of PPGL.

This study sought to evaluate the association between newly-developed significant hypercholesterolemia within one year following living donor liver transplantation (LDLT) and long term outcomes in light of cardiovascular events and graft failure. From October 2003 to July 2017, 877 LDLT recipients were stratified according to development of significant hypercholesterolemia within one year following LDLT. The primary outcome was occurrence of a major adverse cardiac event (MACE), defined as a composite of cardiac death, myocardial infarction, and coronary revascularization after LDLT. The incidence of graft failure, defined as all-cause death or retransplantation, was also compared. A total of 113 (12.9%) recipients developed significant hypercholesterolemia within one year. The differences in incidences of cardiac related events and graft related events began emerging significantly higher in the hypercholesterolemia group after 24 months and 60 months since the LDLT, respectively. After adjustment using the inverse probability of weighting, the hazard ratio (HR) for MACE was 2.77 (95% confidence interval (CI) 1.16–6.61; p = 0.02), while that for graft failure was 3.76 (95% CI 1.97–7.17, p

Glycogen storage disease (GSD) IV is a rare autosomal recessive inherited disorder caused by mutations in the gene coding for glycogen branching enzyme leading to progressive liver disease. GSD IV is associated with mutations in GBE1, which encodes the glycogen branching enzyme. We report a case of GSD IV with rare homozygous mutations in the GBE1 gene (c.791G>A (p.Gly264Glu), which was successfully treated by liver transplantation.

Background Posttransplant liver graft failure occurs most often in male recipients of livers from female donors. The respective role of donor sex itself and the size disparity in graft vessels/bile ducts according to donor sex are unclear. Thus, we aimed to evaluate the importance of donor sex with adjustment for anastomotic size disparity between female and male donor grafts. Methods A total of 309 male patients without hepatic tumors who underwent living donor liver transplantation were analyzed (109 female donors and 200 male donors). The primary outcome was posttransplant graft failure (ie, retransplantation or death). Survival analysis was performed using the Cox model. Analyzed anastomosis-related factors comprised graft weight, number and size of hepatic vessels/bile ducts, and anastomosis techniques. Results Graft failure probabilities at 1, 6, 12, 24, and 60 months posttransplantation were 9.1%, 19.5%, 20.2%, 23.0%, and 27.0%, respectively, with female donors and 2.0%, 5.5%, 8.1%, 10.1%, and 13.5% with male donors (hazards ratio [HR], 2.29; 95% confidence interval [CI], 1.35-3.88; P = 0.002). Multivariable analysis confirmed the significance of donor sex (HR, 2.30; 95% CI, 1.14-4.67; P = 0.021) after adjustment for anastomosis-related factors. All analyzed anastomosis-related factors showed no significant association with graft failure, although size of the graft hepatic artery showed marginal significance (HR, 0.50; 95% CI, 0.25-1.01; P = 0.053). The significance of donor sex was lost when donor was older than 36 to 40 years (age of poor ovarian reserve and the end of female fertility). Our institutional pediatric recipient cohort validated the inferiority of female-to-male donation. Conclusions Donor sex appears to be an independent factor modulating graft failure risk in male liver transplant recipients.

This study aimed to evaluate risk factors and postoperative clinical outcome associated with myocardial injury detected by an elevated high-sensitivity cardiac troponin I (hs-cTnI) immediately after living donor liver transplantation (LDLT).Between January 2011 and December 2016, 313 adult recipients undergoing LDLT, with normal preoperative hs-cTnI were selected. Hs-cTnI level above 0.04 ng/mL according to 99th percentile reference limit was defined as myocardial injury. The recipients were divided into 2 groups according to postoperative hs-cTnI measured immediately after LDLT and postoperative clinical outcome was compared.The primary outcome was composite of death or graft failure during hospital stay. Risk factors associated with myocardial injury during LDLT was also evaluated. Of the 313 recipients with normal preoperative hs-cTnI level, 159 (50.8%) had elevated hs-cTnI level and 154 (49.2%) had normal level after LDLT. The incidence of all-cause death or graft failure during hospital stay was significantly higher in recipients with myocardial injury (1.9% vs 7.6%; hazard ratio, 4.15; 95% confidence interval, 1.01-17.14; P = 0.049). The same result was shown in propensity-matched population (0.9% vs 9.0%; hazard ratio, 9.08; 95% confidence interval, 1.16-71.01; P = 0.04). The results during 1-year follow-up were not consistent. Female sex, ischemia time, and presence of postreperfusion syndrome were independent predictors of myocardial injury during LDLT.Myocardial injury detected by elevation of hs-cTnI level immediately after LDLT was independently associated with adverse outcome during hospital stay.

Purpose Infection remains the main cause of morbidity and mortality in liver transplantation (LT) recipients; however infection is notoriously difficult to diagnose because its usual signs and symptoms of infection may be masked or absent. This study comprises an analysis of bacterial infections in the early period after LT. Methods This is a study of 129 adults who underwent LT from January 2013 to December 2013, and it includes patients who were followed daily from the day of transplantation to 1-week posttransplantation using bacteriological cultures of blood, urine, sputum, and drained ascites. Results The following factors were significantly different between the positive and negative culture groups: living donor LT vs. deceased donor LT (odds ratio [OR], 3.269; P = 0.003), model for end-stage liver disease score (OR, 4.364; P < 0.001), and Child-Pugh classification (P = 0.007). Neither positive culture nor negative culture was associated with infection within 4 weeks of surgery (P = 0.03), and most events were due to surgical complications (75%). Conclusion Since the full effect of immunosuppression is not yet present during the first month after LT, we suggest that the number of bacterial culture test could be reduced such that they are performed every other day depending on patient's situation.

Background and Objective Agitated delirium has frequently occurred after liver transplantation in the intensive care unit (ICU) and sedative agents are used to treat patients. Recently, dexmedetomidine has been considered to be a promising agent for agitated delirium. Methods This study took place between January 2010 and October 2012 and 42 recipients were retrospectively enrolled. Sixteen recipients were enrolled in the dexmedetomidine group and 26 recipients were placed in the haloperidol group. To compare dexmedetomidine and haloperidol, the total ICU length of stay (ICU LOS), the ICU LOS after drug administration, and the supplemental doses of sedative agents used were assessed. The endpoint was discharge from the ICU. Results There were no significant drug-related complications in either group. Dexmedetomidine significantly decreased the ICU LOS and ICU LOS after the occurrence of delirium compared to haloperidol (13.7 days vs. 8.3 days, P = .039, 10.1 days vs. 3.1 days, P = .009). In the dexmedetomidine group, the dose of supplemental midazolam needed was lower than in the haloperidol group (1.5 mg vs. 6.85 mg, P Conclusion Dexmedetomidine is a promising agent for the treatment of ICU-associated agitated delirium in liver transplantation recipients.

Background:Behcet’s disease (BD) is an immune-mediated systemic vasculitis affecting any size of blood vessels. Previous studies showed that BD may involve large arterial vessels [1] but the radiographic outcome has not been well known due to its low prevalence.Objectives:To evaluate the radiographic outcome of vascular BD involving aorta and its major branches and the clinical characteristics of each prognosis group.Methods:We retrospectively analyzed the medical records of patients who visited a single-center tertiary hospital in Seoul, Korea, across a 19-year period (Jan 2002 to Dec 2020). All patients fulfilled the International Criteria for Behcet’s Disease. The patients included in this study had undergone CT angiography (CTA) of the aorta and its major branches at least twice in a 2–5 year interval and showed characteristic vascular involvements (aneurysm, stenosis, occlusion, vessel wall thickening, and thrombosis). Due to lack of the validated definition of radiographic progression of large vessel vasculitis in BD, we defined 20% changes of existing lesions or occurrence of new lesions as a radiographic progression.Results:22 patients with BD met the inclusion criteria. 5 patients (22.7%) progressed radiographically between the initial and follow-up CTA despite low acute phase reactant levels (AUC of ESR and CRP were 13.94 mm/h and 0.32 mg/dl, respectively). Aneurysm was the most frequent form of vascular involvement followed by thrombosis (21 [95.5%] and 11 [50.0%] patients, respectively, Table 1). Patients with radiographically progressive disease had longer disease duration (1.63 vs. 6.61 years, p=0.010) at initial CTA evaluation. Other clinical characteristics, including ESR, CRP, medication use, and follow up duration, were not different between two groups (Table 2).Table 1.Radiographic characteristics of the cohort.OverallNot progressedProgressedpn22175Aneurysm (%)21 (95.5)16 (94.1)5 (100.0)>0.999Stenosis (%)5 (22.7)4 (23.5)1 (20.0)>0.999Occlusion (%)5 (22.7)5 (29.4)0 (0.0)0.440Wall thickening (%)4 (18.2)4 (23.5)0 (0.0)0.589Thrombosis (%)11 (50.0)9 (52.9)2 (40.0)>0.999Conclusion:A considerable number of vascular BD patients involving aorta and its major branches progressed radiographically despite low disease activity. Radiographically progressed patients had longer disease duration, but other clinical characteristics were not significantly different whether progressed or not.References:[1]Kural-Seyahi, Emire MD et al. The Long-Term Mortality and Morbidity of Behçet Syndrome. Medicine. 2003 Jan;82(1):60-76.Table 2.Clinical characteristics of the cohort.OverallNot progressedProgressedpn22175Sex (Male) (%)22 (100.0)17 (100.0)5 (100.0)NAAge (yr)46.43 (7.71)45.06 (8.06)51.10 (4.03)0.126Disease duration (yr)2.77 (3.99)1.63 (2.66)6.61 (5.61)0.01HTN (%)5 (22.7)4 (23.5)1 (20.0)>0.999DM (%)1 (4.5)1 (5.9)0 (0.0)>0.999Dyslipidemia (%)6 (27.3)5 (29.4)1 (20.0)>0.999CKD (%)7 (31.8)4 (23.5)3 (60.0)0.321BMI (kg/m2)42.91 (91.28)48.23 (103.94)24.82 (1.69)0.626AUC of CRP (mg/dl)0.32 (0.37)0.31 (0.41)0.37 (0.12)0.758AUC of ESR (mm/h)13.94 (11.40)13.30 (12.77)16.12 (4.66)0.638Immunosuppressive agent use (%)18 (81.8)14 (82.4)4 (80.0)>0.999Steroid use (%)22 (100.0)17 (100.0)5 (100.0)NAf/u duration (yr)3.54 (0.80)3.56 (0.79)3.50 (0.92)0.885Data are presented as mean (SD) unless otherwise specifiedDisclosure of Interests:None declared

To investigate and compare ultrasound (US) findings for the diagnosis of biliary atresia (BA) in infants younger than 30 days with those of infants older than 30 days. From 2000 to 2015, we reviewed hepatobiliary US images in 12 BA infants younger than 30 days (younger BA group) and 62 BA infants older than 30 days (older BA group) before Kasai procedure. Eight (67%) of younger BA group underwent follow-up US examinations before Kasai procedure. Our review of the images focused on triangular cord sign, gallbladder (GB) abnormalities, vascular changes, and signs of portal hypertension. The triangular cord sign was present in 17% of younger BA group and in 56% of older BA group (P=.024). GB abnormalities were commonly identified in both groups. The hepatic artery diameter was significantly smaller in younger BA group than in older BA group (P

Background Liver transplantation (LT) is thought to resolve cognitive deficit due to hepatic encephalopathy (HE). The aim of this study was to determine the factors associated with the outcomes of patients with HE after LT. Methods The authors reviewed the medical records of 388 patients with HE who underwent LT from 1996 to 2014. Results There were 282 patients with grade 1–2 HE and 106 patients classified as grade 3–4. Patients in the latter group had a tendency for a more decompensated hepatic condition than patients with grade 1–2 HE. HE sequelae were only associated with grade 3–4 HE with borderline significance (P = .05). The cumulative 1-, 3-, and 5-year overall survival (OS) of patients with grade 1–2 HE were 81.9%, 77.3%, and 74.6%, whereas those of in patients with grade 3–4 HE were 77.4%, 73.3%, and 72.2%, respectively (P = .75). Conclusion The sequelae of HE were only associated with the grade 3–4 HE. Aggressive treatment of HE prior to LT may prevent patients from deteriorating into high-grade HE, which could further contribute to improving the outcomes after LT.

Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) are difficult to manage with very poor survival and due to universal recurrence after liver transplantation, they have been excluded from indication. Conformer radiation therapy (RT) has been shown to be effective in the treatment of HCC but only few trials have been reported as bridge to liver transplantation (LT) in HCC with PVTT. The purpose of our study was to evaluate the possibility of applying living donor liver transplantation (LDLT) following successful downstaging using RT in advanced HCC with PVTT. Among 1360 patients who received LT at our institution between May 1996 and March 2013, 5 received RT and they were compared with a propensity score matched group of 10 patients receiving RT alone according to sex, age, tumor size and number, dose of RT, level of AFP and location of PVTT. Objective tumor response after RT was evaluated with CT and/or MRI according to modified RECIST criteria. There is no difference in clinical characteristics between both groups. Two recipients showed disease progression, but in RT alone group, all patients are shown tumor ingrowths or intra-, extra-hepatic metastasis. LDLT following RT group's OS was 1055 days and that of RT alone group's was 367 days with significant statistically difference. Conclusion: LDLT following RT can be treatment of choice for PVTT in selective patients like solitary HCC with below Vp3 PVTT and good tumor response, and we suggest that this warrants further testing in a randomized, controlled, multi-center trial. And when doing bile duct anastomosis in RT recipients, hepaticojejunostomy was recommended to prevent biliary complication. This article is protected by copyright. All rights reserved.

BACKGROUND Isoniazid (INH) prophylaxis (Px) has good efficacy for preventing tuberculosis (TB) in the general population. However, its use for the treatment of latent TB infections (LTBI) in liver transplant (LT) recipients is challenging because little is known about INH-induced hepatotoxicity in graft recipients. We evaluated the efficacy and safety of INH Px in LT recipients. MATERIAL AND METHODS From March 2008 to December 2012, we retrospectively reviewed data on 277 patients who received LT at a single center. We examined the results of tuberculin skin tests and interferon-γ release assays, use of INH, INH-induced hepatotoxicity, and post-LT TB occurrence. RESULTS Among 277 recipients, 7 cases of post-transplant TB were detected (2.52%). Seventeen patients received post-transplant INH Px. Among INH Px recipients, post-LT TB infection did not occur. Hepatotoxicity after INH Px was significantly lower in the patients who received INH Px at an aspartate aminotransferase (AST) level that was less than 50 U/L than in those who received INH Px at an AST level that was more than 50 U/L (P=0.046, 0.002). CONCLUSIONS INH is likely to be effective for preventing post-LT TB recurrence in LTBI. However, because of INH-induced hepatotoxicity, it is better to avoid using it in the early post-LT period and to wait to initiate INH Px until liver function is stable in LT recipients.

A right liver graft with multiple hepatic artery (HA) stumps can be found in approximately 5% of living donor liver transplantation (LDLT) using a right lobe graft. From January 2000 to June 2014, 1149 patients underwent LDLT procedures. Thirty patients with LDLT using a right lobe graft with multiple HA stumps and 149 patients with LDLT using a right lobe graft with a single HA stump were enrolled. These patients were divided into 3 groups: single HA (group 1, n = 149), multiple HAs with total reconstruction (group 2, n = 19), and multiple HAs with selective partial reconstruction (group 3, n = 11). Selective partial reconstruction was performed only when pulsatile back-bleeding was confirmed after larger HA reconstruction and sufficient intrahepatic arterial flow was confirmed by Doppler ultrasound (DUS). In group 2, the donor HAs were smaller (P < .001), and HA reconstruction took longer (P < .001). However, there was no significant difference among the groups regarding the arterial complication rate, biliary complication rate, and patient and graft survival. In conclusion, selective partial reconstruction of HA stumps for LDLT using a right lobe graft was feasible when intrahepatic arterial communication was confirmed by pulsatile back-bleeding from the smaller artery and DUS. Liver Transplantation 22 1649-1655 2016 AASLD.

Background Since Rothenberg first performed thoracoscopic repair for esophageal atresia with distal tracheoesophageal fistula (EA/TEF) successfully in 2000, thoracoscopic repair has achieved status as a routine procedure worldwide. Previously, an international multicenter study reported that this procedure was not inferior to conventional open surgery. However, thoracoscopic surgery is a highly difficult operation for surgeons and anesthesiologists; as a result, the safety and efficacy of the surgery is still under debate. Considering these circumstances, the purpose of this study was to analyze the results of single-center thoracoscopic surgery and to compare the outcomes relative to the patient’s weight at the time of surgery. Methods We retrospectively analyzed patients with EA/TEF who underwent thoracoscopic surgery in a single center between October 2008 and February 2017. Results In total, 41 cases of thoracoscopic repair of EA/TEF were performed. Upon subgrouping by over and under 2000 g of body weight at the time of operation, 34 were found to be over 2000 g and seven were under 2000 g. Intraoperative factors and events were not significantly different between the two groups. Additionally, most of the postoperative outcomes, including the rate of postoperative leakage and strictures, showed no difference. On the other hand, the under 2000 g group had more gastroesophageal reflux requiring fundoplication than did the heavier group (P = 0.04). Conclusions The results of this center’s thoracoscopic repair of EA/TEF were not inferior to other centers’ outcomes. Additionally, the intraoperative and postoperative outcomes were similar despite differences in weight at operation. Therefore, thoracoscopic repair might be a feasible surgical option for infants weighing less than 2000 g when performed by a surgeon and anesthesiologist team who are experienced in pediatric thoracoscopic surgery.

Purpose It is not easy to determine whether balloon angioplasty or stenting should be performed in patients with portal vein stenosis after liver transplantation. We aimed to propose appropriate indication by evaluating long-term outcomes of balloon angioplasty and stent insertion in adult liver transplant patients. Methods We retrospectively reviewed 31 patients with portal vein stenosis among 1369 patients who underwent adult liver transplantation from January 2001 to December 2015. When stenosis was confirmed by venography, angioplasty was performed first. When there was no flow improvement or pressure gradient was not decreased after angioplasty, stent insertion was performed. We also performed primary stent insertion without angioplasty for diffuse stenosis, kinking, external compression, and near occlusion of portal vein in venography. We assessed patency in patients who underwent percutaneous transluminal angioplasty and stent insertion through regular outpatient follow-up and evaluated technical and clinical success and long-term results. Results Technical success was 85% and 100% in balloon angioplasty and stent insertion, respectively. Clinical success was achieved in 78% of balloon angioplasties and in 100% of stent insertions. At 1, 5, and 10 years after balloon angioplasty, patency rates were 87%, 82%, and 68% respectively, and the rates of stent patency were all 100%. Portal vein size measured during the operation of patients with and without recurrence were 19±4.2 mm and 19±3.0 mm (P = 0.956), respectively. The balloon size of patients with and without recurrence were 11±1.95 mm and 14±1.66 mm, respectively (P = 0.013), when balloon angioplasty was performed after stenosis diagnosis. Conclusion Stent insertion can be considered when fibrotic changes are expected due to repeated inflammation and when the balloon size to be used is small. Balloon angioplasty seems less risky for anastomotic ruptures in portal vein stenosis in the early post liver transplantation period.

Donor safety and graft results of pure laparoscopic living donor right hepatectomy (LLDRH) have previously been compared with those of open living donor right hepatectomy (OLDRH). However, the clinical outcomes of recipients at 1-year follow-up have never been accurately compared. We aimed to compare 1-year outcomes of recipients of living donor right liver transplantation (LRLT) using pure LLDRH and OLDRH. From May 2013 to May 2017, 197 consecutive recipients underwent LRLT. Donor hepatectomies were performed either by OLDRH (n = 127) or pure LLDRH (n = 70). After propensity score matching, 53 recipients were included in each group for analysis. The clinical outcomes at 1-year follow-up were compared between the 2 groups. The primary outcome was recipient death or graft failure during the 1-year follow-up period. In the propensity-matched analysis, the incidence of death or graft failure during the 1-year follow-up period was not different between the 2 groups (3.8% versus 5.7%; odds ratio [OR], 1.45; 95% confidence interval [CI], 0.24-8.95; P = 0.69). However, the composite of Clavien-Dindo 3b-5 complications was more frequent in the pure LLDRH group (OR, 2.62; 95% CI, 1.15-5.96; P = 0.02). In conclusion, although pure LLDRH affords a comparable incidence of fatal complications in recipients, operative complications may increase at the beginning of the program. The safety of the recipients should be confirmed to accept pure LLDRH as a feasible option.

Background/Aims: The relationship between patient survival and biopsy-proven acute rejection (BPAR) in liver transplant recipients with hepatitis C remains unclear. The aims of this study were to compare the characteristics of patients with and without BPAR and to identify risk factors for BPAR. Methods: We retrospectively reviewed the records of 169 HCV-RNA-positive patients who underwent LT at three centers. Results: BPAR occurred in 39 (23.1%) of the HCV-RNA-positive recipients after LT. The 1-, 3-, and 5-year survival rates were 92.1%, 90.3%, and 88.5%, respectively, in patients without BPAR, and 75.7%, 63.4%, and 58.9% in patients with BPAR (P

Partial liver grafts used in living donor liver transplantation (LDLT) may have multiple hepatic artery (HA) stumps. This study was designed to validate the safety of partial reconstruction of multiple HAs in pediatric LDLT cases. From January 2000 to June 2014, 136 pediatric LDLT recipients were categorized into three groups: single HA group (Group 1, n = 74), multiple HAs with total reconstruction group (Group 2, n = 23), and multiple HAs with partial reconstruction group (Group 3, n = 39). Partial reconstruction was performed only when there was pulsatile back-bleeding after larger HA reconstruction and sufficient intrahepatic arterial flow was confirmed by Doppler ultrasound (DUS). There was no significant difference in biliary complication rate, artery complication rate, patient survival, and graft survival among these groups. Risk factor analysis revealed that the presence of multiple HAs and partial reconstruction of multiple HAs were not risk factors of biliary anastomosis stricture. In conclusion, partial reconstruction of HAs during pediatric LDLT using a left liver graft with multiple HA stumps does not increase the risk of biliary anastomosis stricture or affect graft survival when intrahepatic arterial communication is confirmed by pulsatile back-bleeding and DUS.

International audience; BACKGROUND & AIMS: Cytokines are key molecules implicated in the defense against virus infection. Tumor necrosis factor-alpha (TNF-alpha) is well known to block the replication of hepatitis B virus (HBV). However, the molecular mechanism and the downstream effector molecules remain largely unknown. METHODS: In this study, we investigated the antiviral effect and mechanism of p22-FLIP (FLICE-inhibitory protein) by ectopic expression in vitro and in vivo. In addition, to provide the biological relevance of our study, we examined that the p22-FLIP is involved in TNF-alpha-mediated suppression of HBV in primary human hepatocytes. RESULTS: We found that p22-FLIP, a newly discovered c-FLIP cleavage product, inhibited HBV replication at the transcriptional level in both hepatoma cells and primary human hepatocytes, and that c-FLIP conversion to p22-FLIP was stimulated by the TNF-alpha/NF-kappaB pathway. p22-FLIP inhibited HBV replication through the upregulation of HNF3beta but downregulation of HNF4alpha, thus inhibiting both HBV enhancer elements. Finally, p22-FLIP potently inhibited HBV DNA replication in a mouse model of HBV replication. CONCLUSIONS: Taken together, these findings suggest that the anti-apoptotic p22-FLIP serves a novel function of inhibiting HBV transcription, and mediates the antiviral effect of TNF-alpha against HBV replication

The use of hepatitis B core antibody-positive (HBcAb+) grafts for liver transplantation (LT) has the potential to safely expand the donor pool, as long as proper prophylaxis against de novo hepatitis B (DNHB) is employed. The aim of this study was to characterize the longterm outcome of pediatric LT recipients of HBcAb + liver grafts under a prophylaxis regimen against DNHB using hepatitis B virus (HBV) vaccine and hepatitis B immunoglobulin (HBIG). From June 1996 to February 2013, 49 patients receiving pediatric LT at our center were from HBcAb + donors. Forty-one patients who received DNHB prophylaxis according to our protocol were included in this analysis. Our DNHB prophylaxis protocol consists of HBV vaccine intramuscular injections given intermittently to maintain anti-hepatitis B surface antibody (HBsAb) titers above 100 IU/L. HBIG was also used during the first posttransplant year with a target anti-HBsAb titer level above 200 IU/L. There were 19 boys and 22 girls. Median age was 1.0 year (range, 4 months to 16 years). Median follow-up time was 66 months after transplant. Median annual number of HBV vaccine injections was 0.8 per year (range, 0-1.8 per year). Four patients did not require any HBV vaccine injections during follow-up. One patient with DNHB was encountered during the follow-up period (1/41, 2.4%). DNHB was diagnosed at 3.5 years after transplant, when hepatitis B surface antigen was positive upon routine follow-up serologic testing. Anti-HBsAb titer was 101.5 IU/L at the time. No grafts were lost because of DNHB-related events. Overall survival of the 41 recipients of HBcAb + grafts who received DNHB prophylaxis was 92.3% at 10 years after transplant. In conclusion, longterm prophylaxis against DNHB with HBV vaccine in pediatric LT recipients of HBcAb + grafts was safe and effective in terms of DNHB incidence as well as graft and patient survival.