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There is a nationwide shortage of organs available for liver transplantation. Living donors help meet this growing demand. Not uncommonly, donors will have positive autoantibodies. However, it is unclear whether donor positive autoantibodies are correlated with worse outcomes following living liver donor transplantations.To analyze the significance of positive autoantibodies in donors on post-transplant outcomes in recipients.We performed a retrospective review of living liver donors who had undergone liver transplantation between January 1, 2012 and August 31, 2021. Demographic characteristics and pre-transplant data including antinuclear antibodies (ANA) and anti-smooth muscle antibody titers were collected in donors. Outcomes of interest were post-transplantation complications including mortality, biliary strictures, biliary leaks, infection, and rejection. Pediatric recipients and donors without measured pre-transplant autoantibody serologies were excluded from this study.172 living donor liver transplantations were performed during the study period, of which 115 patients met inclusion criteria. 37 (32%) living donors were autoantibody-positive with a median ANA titer of 1:160 (range 1:80 to 1:1280) and median anti-SMA titer of 1:40 (range 1:20 to 1:160). There were no significant differences in baseline demographics between the autoantibody positive and negative donors. Post-transplantation rates of death (Isolated pre-transplant autoantibody positivity is not correlated to worse post-transplant outcomes in living liver donor transplants.

Introduction Diffuse splanchnic vein thrombosis (DSVT) remains a serious challenge in liver transplantation (LT). Reno-portal anastomosis (RPA) has previously been reported as a valid option for management of patients with DSVT during LT. The aim of this study was to evaluate posttransplant renal function and surgical outcomes of patients with DSVT who underwent RPA during LT. Methods Between January 2005 and December 2017, 1,270 patients underwent LT at our institution, including 16 with DSVT managed with RPA (RPA group). We compared renal function and surgical outcomes in these patients to outcomes in 48 propensity-score (PS) matched patients without thrombosis (control group), using a 1:3 matching model. Results The two groups had similar rates of postoperative portal vein thrombosis (PVT), renal dysfunction as measured by estimated glomerular filtration rate (eGFR), and overall postoperative complications (Clavien grade III), although the RPA group had a higher incidence of postoperative upper gastrointestinal (GI) bleeding (31.3% vs 4.2%; p=0.009) that had no clinical consequence. There were no significant differences in five-year graft and patient survival rates between the groups (p=0.133 and p=0.166, respectively). Conclusion RPA is an established technique in the management of patients with DSVT during LT, with comparable outcomes to patients without thrombosis. Our report is the first to demonstrate similar surgical outcomes, including long-term renal function, in LT recipients with or without RPA.

Objective The Expert Consensus Guidelines initiative on MIDH for LDLT was organized with the goal of safe implementation and development of these complex techniques with donor safety as the main priority. Background Following the development of minimally invasive liver surgery, techniques of MIDH were developed with the aim of reducing the short- and long-term consequences of the procedure on liver donors. These techniques, although increasingly performed, lack clinical guidelines. Methods A group of 12 international MIDH experts, 1 research coordinator, and 8 junior faculty was assembled. Comprehensive literature search was made and studies classified using the SIGN method. Based on literature review and experts opinions, tentative recommendations were made by experts subgroups and submitted to the whole experts group using on-line Delphi Rounds with the goal of obtaining >90% Consensus. Pre-conference meeting formulated final recommendations that were presented during the plenary conference held in Seoul on September 7, 2019 in front of a Validation Committee composed of LDLT experts not practicing MIDH and an international audience. Results Eighteen Clinical Questions were addressed resulting in 44 recommendations. All recommendations reached at least a 90% consensus among experts and were afterward endorsed by the validation committee. Conclusions The Expert Consensus on MIDH has produced a set of clinical guidelines based on available evidence and clinical expertise. These guidelines are presented for a safe implementation and development of MIDH in LDLT Centers with the goal of optimizing donor safety, donor care, and recipient outcomes.

BACKGROUND Laparoscopic donor hepatectomy (LDH) for living donor liver transplantation has been performed in several specialized institutes. Surgical outcomes of LDH have shown comparable results to open donor hepatectomy (ODH), but the quality of life (QOL) after LDH is not known. This prospective questionnaire-based study was performed to assess health status and QOL of live liver donors before and after donor hepatectomy (DH). MATERIAL AND METHODS From May 2017 to February 2020, questionnaire items such as the Enhanced Recovery after Surgery mobility scale (EMS), Body Image Questionnaire, and EQ-5D-3L were examined up to 1 year after DH to respectively evaluate postoperative recovery, body image satisfaction, and health status. RESULTS During the study period, 45 laparoscopic DH (LDH) donors and 2 open DH (ODH) donors were finally fully evaluated. The LDH group had a significantly higher mean EMS than ODH on postoperative day (POD) 5, and 7 (P=0.011, and P=0.004, respectively). Body image scores of the LDH group were significantly higher than that of the ODH group at 1 month after DH (17.8 vs 15.0, P=0.017). There were 45 LDH donors who recovered to preoperative values at 6 months and 1 month after DH, with no statistically significant difference in EQ-5D-3L index value and visual analogue scale (P=0.059 and P=0.217, respectively). CONCLUSIONS Within 1 month after DH, LDH donors showed faster mobility recovery and body image satisfaction to the level of preoperative status than ODH. LDH donors recovered to preoperative health status within 6 months, in accordance with previous studies of ODH donors.

Acute liver failure is a rare but life-threatening medical emergency. Despite advancements in medical management, mortality rates of acute liver failure remain high. Currently, liver transplant is the only definitive therapeutic option available. High-volume plasma exchange has been shown to increase transplant-free survival in patients with acute liver failure before liver transplant. However, the occurrence of infectious complications in patients who receive this treatment has not been well studied. We report 2 cases of severe opportunistic infections occurring within 30 days of transplant in patients who underwent high-volume plasma exchange before liver transplant.

Backgrounds/Aims While minimal invasive surgery has become popular, the feasibility of laparoscopy for liver cavernous hemangioma has not been shown. Methods Patients who underwent hepatectomy for liver cavernous hemangioma from January 2008 to February 2019 at the Samsung Medical Center were reviewed. Patients who underwent trisectionectomy were excluded. Background characteristics, along with operative and postoperative recovery, were compared between the laparoscopy and open surgery groups. Results Forty-three patients in the laparoscopy group and 33 patients in the open surgery group were compared. The differences in the background characteristics were presence of symptoms (14.6% in laparoscopy vs. 57.1% in open, p

Purpose Hepatocellular carcinoma (HCC) is rare in HCV patients without cirrhosis, and little is known about the postoperative results of these patients. The present study compares the outcomes of cirrhotic and non-cirrhotic groups after liver resection (LR) in solitary HCV-related HCC patients and identifies risk factors for prognosis according to the presence or absence of cirrhosis in these patients. Methods Two hundred and 7 adult hepatectomy patients with treatment-naïve solitary HCV-related HCC were identified prospectively at our institution between July 2005 and May 2019. Results The non-cirrhotic group had better liver function than the cirrhotic group based on platelet count, liver function tests, liver stiffness measurement, and indocyanine green retention rate at 15 minutes but were older than the cirrhotic group. Consistently, noninvasive markers in the cirrhotic group were significantly higher than in the non-cirrhotic group. The cumulative disease-free survival and overall survival in the non-cirrhotic group were significantly higher than in the cirrhotic group. HCC recurrence was related to major LR and α-FP of >40 ng/mL and death was related to long hospitalization and α-FP of >40 ng/mL in multivariate analysis. Noninvasive markers and the presence of cirrhosis were not related to HCC recurrence or death in multivariate analyses. Conclusion The cirrhotic group showed poor prognosis due to poor liver function after LR compared to the non-cirrhotic group, but this was not sustained in multivariate analysis. The factors influencing HCC recurrence and death were different in the cirrhotic and non-cirrhotic groups.

The feasibility and learning curve of laparoscopic living donor right hepatectomy was assessed.Donors who underwent right hepatectomy performed by a single surgeon were reviewed. Comparisons between open and laparoscopy regarding operative outcomes, including number of bile duct openings in the graft, were performed using propensity score matching.From 2014 to 2018, 103 and 96 donors underwent laparoscopic and open living donor right hepatectomy respectively, of whom 64 donors from each group were matched. Mean(s.d.) duration of operation (252·2(41·9) versus 304·4(66·5) min; P 0·001) and median duration of hospital stay (8 versus 10 days; P = 0·002) were shorter in the laparoscopy group. There was no difference in complication rates of donors (P = 0·298) or recipients (P = 0·394) between the two groups. Total time for laparoscopy decreased linearly (RLaparoscopic living donor right hepatectomy is feasible and an experience of approximately 50 cases may surpass the learning curve.Se evaluó la viabilidad y la curva de aprendizaje de la hepatectomía derecha de donante vivo MÉTODOS: Se llevó a cabo una revisión de los donantes sometidos a hepatectomía derecha por un único cirujano. Las comparaciones entre el abordaje abierto y laparoscópico con respecto a los resultados operatorios, incluyendo el número of aberturas de los conductos biliares en el injerto se realizó utilizando un análisis de emparejamiento por puntaje de propensión.Desde 2014 a 2018, 96 y 103 donantes fueron sometidos a hepatectomía derecho de donante vivo por cirugía abierta y laparoscópica, respectivamente, de los cuales 64 donantes fueron emparejados para ambos grupos. La media del tiempo operatorio (304,3 ± 66,5 versus 252,2 ± 41,9 minutos, P0,001) y la mediana de la estancia hospitalaria fueron más cortas en el grupo de cirugía laparoscópica (10 versus 8 días, P = 0,002). No hubo diferencias entre ambos grupos en las tasas de complicaciones de los donantes (P = 0,298) o receptores (P = 0,394). El tiempo total de la laparoscopia disminuyó linealmente (R2= 0,407, β = -0,914, P = 0,001) y esta disminución comenzó a partir aproximadamente de los 50 casos realizados cuando los casos fueron divididos en cuatro cuartiles (segundo a tercero y tercero a cuarto, P = 0,001 y P = 0,023, respectivamente). Aunque los injertos con aperturas de los conductos biliares fueron más numerosos en el grupo laparoscópico (P = 0,022), no se hallaron diferencias en los dos últimos cuartiles (P = 0,207). CONCLUSIÓN: La hepatectomía derecha de donante vivo por vía laparoscópica es viable, y una experiencia de aproximadamente 50 casos, puede superar la curva de aprendizaje.

Background/Aims: Biliary strictures remain one of the most challenging aspects after living donor liver transplantation (LDLT). The aim of this study was to assess long-term out ­come of endoscopic treatment of biliary strictures occurring after LDLT and to identify risk factors of recurrent biliary stric­ tures following endoscopic retrograde biliary drainage (ERBD) in LDLT. Methods: A total of 1,106 patients underwent LDLT from May 1995 to May 2014. We compared the risk factors between patients with and without recurrent biliary strictures. Results: Biliary strictures developed in 24.0% of patients. Technical success rate of ERBD for biliary stricture after LDLT was 66.2% (145/219). Among 145 patients managed by endoscopic drainage, stricture resolution occurred in 69 with median duration of stent indwelling of 13.6 months (range, 0.5 to 67.3 months), and stricture recurrence was seen in 20 (21.3%) out of 94. The median recurrence-free duration after final endoscopic success was 13.1 months (range, 0.5 to 67.3 months). Older donor age (hazard ratio [HR], 1.10; 95% confidence interval [CI], 1.03 to 1.17; p=0.004) and non-B, non-C liver cirrhosis (HR, 5.10; 95% CI, 1.10 to 25.00; p=0.043) were associated with higher recurrence of biliary stricture. Conclusions: Long-term stricture resolution rate after ERBD insertion for biliary stricture occurring after LDLT was 73.4%. Clinicians should pay careful attention during following-up to decide when to remove ERBD in patients who have factors associated with recurrent biliary strictures. (Gut Liver 2020;14:125-134)

Background: Prolonged-release tacrolimus is associated with better long-term graft and patient survival than the immediate-release formulation in liver transplant patients. However, no clinical data are available to assess the efficacy and safety of early conversion from twice-daily, immediate-release tacrolimus to once-daily, prolonged-release tacrolimus in de novo liver transplant recipients in Korea. Methods: A 24-week, randomized, open-label study was conducted in 36 liver transplant recipients. All patients received immediate-release tacrolimus (0.1-0.2 mg/kg/day, divided into two doses) for 4 weeks after transplantation, at which time 50% of the patients were converted, at a ratio of 1 mg to 1 mg, to prolonged-release tacrolimus (once-daily). The primary efficacy endpoint was the incidence of biopsy-confirmed acute rejection (BCAR) from weeks 4 to 24 after transplantation (per-protocol set). Medication adherence, adverse event profiles, laboratory tests, vital signs, and physical changes were also recorded. Results: BCAR frequency at 24 weeks was similar between the two treatment groups; two cases (mean±standard deviation, 0.14±0.53 cases) of BCAR were reported in one patient treated with prolonged-release tacrolimus (n=14), while no such cases were reported among patients treated with immediate-release tacrolimus (n=12). The tacrolimus blood concentration at weeks 12 and 24, medication adherence, and adverse event profiles were also similar between the formulations, with no unusual laboratory test results, vital signs, or physical changes reported. Conclusions: Early conversion to a simplified, once-daily, prolonged-release tacrolimus regimen may be an effective treatment option for liver transplant recipients in Korea. Larger-scale studies are warranted to confirm non-inferiority to immediate-release tacrolimus formulation in de novo liver transplant recipients.

Most management guidelines and much of the available clinical trial evidence for immunosuppressants in liver transplantation (LT) pertain to Western practice. While evidence from Western studies may not translate to Asian settings, there is a paucity of Asian randomized controlled trials of immunosuppression in liver recipients. Nonetheless, there are notable differences in the indications and procedures for LT between Western and Asian settings. The Asian Liver Transplant Network held its inaugural meeting in Singapore in November 2016 and aimed to provide an Asian perspective on aspects of immunosuppression following LT. Because of their importance to outcome following LT, the meeting focused on (1) reducing the impact of renal toxicity, (2) hepatocellular carcinoma recurrence, and (3) nonadherence with immunosuppressant therapy.

BACKGROUND The purpose of this study was to investigate the feasibility of using intraoperative ultrasonography as a guidance in dividing bile duct during laparoscopic donor hepatectomy. MATERIAL AND METHODS Cases of living liver donors who underwent laparoscopic living donor hepatectomy from May 2013 to December 2017 were reviewed. Operative and postoperative data were compared between donors with intraoperative ultrasonography and donors with intraoperative cholangiography. For analyzing whether bile duct division was performed successfully, anatomical type and number of bile duct openings were reviewed. When the number of bile ducts were achieved as expected, it was considered "successful". RESULTS Intraoperative cholangiography was used in 67 donors (62.6%) while intraoperative ultrasonography was used in 36 donors (33.6%). Mean operation time was 405.0±76.2 minutes versus 275.1±37.5 minutes, P

Purpose Little is known about liver resection (LR) in hepatocellular carcinoma (HCC) patients older than 75 years of age. This study aimed to compare the postoperative and long-term outcomes of hepatectomy in this patient population according to operation period. Methods This study included 130 elderly patients who underwent LR for solitary treatment-naive HCC between November 1998 and March 2020. Group 1 included patients who underwent LR before 2016 (n = 68) and group 2 included those who underwent LR during or after 2016 (n = 62). Results The proportion of major LR, anatomical LR, and laparoscopic LR (LLR) in group 1 was significantly lower than those in group 2. Also, the median operation time, amount of blood loss, hospitalization length, rates of intraoperative blood transfusion, and complications in group 2 were less than those in group 1. In the subgroup analysis of group 1, high proteins induced by vitamin K absence or antagonist-II, long hospitalization, and LLR were closely associated with mortality. In the subgroup analysis of group 2, however, none of the factors increased mortality. Nevertheless, the presence of tumor grade 3 or 4 and the incidence of microvascular invasion were higher in group 1 than in group 2, and the disease-free survival and overall survival were better in group 2 than in group 1 because of minimized blood loss and quicker recovery period by increased surgical techniques and anatomical approach, and LLR. Conclusion LR in elderly HCC patients has been frequently performed recently, and the outcomes have improved significantly compared to the past.

Cytochrome P450 (CYP) 3A5 polymorphism influences tacrolimus metabolism, but its effect on the drug pharmacokinetics in liver transplant recipients switched to once-daily extended-release formulation remains unknown. The aim of this study is to analyze the effect of CYP3A5 polymorphism on liver function after once-daily tacrolimus conversion in liver transplant patients. A prospective open-label study included 60 stable liver transplant recipients who underwent 1:1 conversion from twice-daily tacrolimus to once-daily tacrolimus. All participants were genotyped for CYP3A5 polymorphism. The study was registered at ClinicalTrials.gov (NCT 02882113). Twenty-eight patients were enrolled in the CYP3A5 expressor group and 32 in the non-expressor group. Although there was no statistical difference, incidence of liver dysfunction was higher in the expressor group than in the non-expressor group when converted to once-daily extended-release tacrolimus (p = 0.088). No biopsy-proven acute rejection, graft failure, and mortality were observed in either group. The decrease in dose-adjusted trough level (−42.9% vs. −26.1%) and dose/kg-adjusted trough level of tacrolimus (−40.0% vs. −23.7%) was significantly greater in the expressor group than in the non-expressors after the conversion. A pharmacokinetic analysis was performed in 10 patients and tacrolimus absorption in the non-expressor group was slower than in the expressor group. In line with this observation, the area under the curve for once-daily tacrolimus correlated with trough level (Cmin) in the non-expressors and peak concentration (Cmax) in the expressors. CYP3A5 genotyping in liver transplant recipients leads to prediction of pharmacokinetics after switching from a twice-daily regimen to a once-daily dosage form, which makes it possible to establish an appropriate dose of tacrolimus.

To analyze the effects of CYP3A5 polymorphism on liver function after LT and to characterize the pharmacokinetics of tacrolimus after conversion from a twice-daily regimen to a once-daily extended-release formulation. A prospective open-label study included 60 stable liver transplant recipients who underwent 1:1 conversion from twice-daily tacrolimus to once-daily tacrolimus. All participants were genotyped for CYP3A5 polymorphism. The study was registered at ClinicalTrials.gov (NCT 02882113). Twenty-eight patients were enrolled in the CYP3A5 expressor group and 32 in the non-expressor group. Although there was no statistical difference, incidence of liver dysfunction was higher in the expressor group than in the non-expressor group when converted to once-daily extended-release tacrolimus (P=0.088). No biopsy-proven acute rejection, graft failure, and mortality were observed in either group. The decrease in dose-adjusted trough level (- 42.9% vs. - 26.1%) and dose/kg-adjusted trough level of tacrolimus (- 40.0% vs. - 23.7%) was significantly greater in the expressor group than in the non-expressors after the conversion. The absorption of the tacrolimus in the non-expressor group was slower than in the expressors. In line with this observation, the AUC for once-daily tacrolimus correlated with Cmin in the non-expressors and Cmax in the expressors. Determination of CYP3A5 genotype in liver transplant recipients might be helpful in prediction of tacrolimus pharmacokinetics after conversion from a twice-daily regimen to a once-daily formulation.

It remains unclear whether the short-term benefits and long-term outcomes of laparoscopic liver resection (LLR) accrue to elderly patients with medical comorbidities. The aim of the present study was to compare the outcomes between LLR and open liver resection (OLR) in elderly patients (&ge, 65 years) with solitary, treatment-na&iuml, ve solitary hepatocellular carcinoma (HCC). From January 2013 to August 2017, 256 elderly patients with solitary treatment-naive HCC underwent liver resection. All patients were Child&ndash, Pugh class A and older than 65 years. The OLR and LLR groups contained 160 and 96 patients, respectively. The median tumor size in the OLR group was significantly larger than that in the LLR group (3.9 vs. 2.6 cm), but the tumor size did not differ between the two groups after matching. The median operation time, blood loss, transfusion rate, and postoperative complications in the OLR group did not differ from those in the LLR group, but the operation time in the LLR group was longer than that in the OLR group after matching. The median hospitalization in the LLR group was significantly shorter than that in the OLR group. Disease-free survival (DFS) in the LLR group was better than that in the OLR group before and after matching, but the difference was not significant. Patient survival (PS) in the LLR group was similar to that in the OLR group. LLR is feasible and safe for elderly patients with solitary, treatment-na&iuml, ve HCC. The short- and long-term benefits of LLR are evident in geriatric oncological liver surgery patients.

BACKGROUND: Insufficient data are available about patient survival following different treatments for recurrent hepatocellular carcinoma (HCC) after primary hepatectomy. We retrospectively investigated the effectiveness of various treatment methods. METHODS: From 2005 to 2011, 515 hepatectomy patients who developed recurrence within the Milan criteria (MC) were grouped by treatment modality into living donor liver transplantation (LDLT), hepatic re-resection (RR), radiofrequency ablation (RFA), transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI), and combination of TACE and RFA (TACE-RFA) group. RESULTS: Disease-free survival and patient survival after first HCC recurrence were compared according to treatment strategies. TACE (n=230, 44.7%), RFA (n=171, 33.2%), PEI (n=35, 6.8%), RR (n=45, 8.7%), salvage LDLT (n=21, 4.1%), and TACE-RFA (n=13, 2.5%) were all used as the first treatment in recurrent HCC within the MC. The disease-free survival curve from 1(st) HCC recurrence in the PEI group was lower than in the other groups (P=0.004). The RR, salvage LDLT, and TACE-RFA groups showed good long-term prognosis. The patient survival rate at 3 years after 1(st) HCC recurrence was 45.2% in TACE, 51.7% in RFA, 39.8% in PEI, 38.2% in RR, 81.4% in salvage LDLT, and 80.8% in the TACE-RFA group. Thus, the patient survival curve in the salvage LDLT and TACE-RFA groups was higher than in the other groups (P

Purpose The proportion of liver recipients with HCV is gradually increasing in Korea. Limited data are available regarding the efficacy of direct antiviral agents (DAAs) in liver transplant recipients in Asia. We aimed to assess the efficacy and safety of DAAs in HCV-infected liver recipients in Korea. Methods Forty HCV-infected patients from 2 centers received DAAs in the pretransplant or posttransplant period between May 2015 and November 2016. Results DAA was administered in the pretransplant period in 6 patients and the posttransplant period in 34 patients. Dalastavir and asunaprevir (n = 2) and sofosbuvir/ledipasvir and ribvarin (n = 4) were used in the pretransplant period. HCV RNA was not detected before liver transplantation in all patients. Sustained virological response (SVR) at 12 and 24 weeks after liver transplantation was 100%. In the posttransplant period, 33 of 34 patients received sofosfovir-based therapy. SVR at 12 weeks in those patients was 94%. Recurrent virologic relapse developed in 2 patients because of HCC recurrence or treatment failure. Adverse events included anemia (n = 2) and abdominal discomfort (n = 1). Conclusion DAAs are an effective and well-tolerated treatment for HCV-infected recipients in Korea.

Background Laparoscopic liver resection has been reported as a safe and effective approach for the management of hepatocellular carcinoma (HCC). However, its perioperative and oncological outcomes have not been evaluated in left hepatectomy patients. The aim of the present study is to compare the outcomes of left hepatectomy through laparoscopic and open approaches in left HCC. Methods From December 2012 to October 2016, laparoscopic left hepatectomy (LLH) was performed in 40 patients and open left hepatectomy (OLH) was performed in 80 patients. All clinical data were analyzed retrospectively. Propensity score matching of patients in a 1:1 ratio was conducted based on tumor size and presence of microvascular invasion. Results Tumor size and presence of microvascular invasion were higher in the OLH group than the LLH group (P

Purpose Although few hepatectomy patients develop unexpected early diffuse and multinodular recurrence in the remnant liver, the prognosis in such cases is often dismal. The aim of this study was to evaluate the risk factors of early disseminated multinodular hepatocellular carcinoma (HCC) recurrence within 3 months after liver resection for solitary HCC. Methods Eighty-four patients who were diagnosed with recurrent HCC within 3 months after hepatectomy for solitary HCC were retrospectively reviewed. Disseminated HCC recurrence was defined as more than 10 tumors in both lobes and total tumor size >10 cm. Results Preoperative α-FP level, incidence of poor tumor grade, and presence of portal vein tumor thrombosis were higher in the patients with disseminated HCC recurrence than in those without disseminated HCC recurrence (P < 0.05). Multivariate analysis showed that α-FP >1,000 ng/dL was a predisposing factor of disseminated HCC recurrence within 3 months after liver resection. The overall survival rate for patients without disseminated HCC recurrence was higher than that for patients with disseminated HCC recurrence (P < 0.001). Conclusion Early disseminated multinodular HCC recurrence in hepatectomy patients was associated with preoperative α-FP >1,000 ng/dL. Such patients should be frequently evaluated for the early detection of recurrent HCC for early intervention.

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: With improvements in living donor liver transplantation (LDLT) techniques and the increased experience of surgeons in laparoscopic major liver resection, laparoscopic donor hepatectomy is performed increasingly. Therefore, expert opinion on this procedure is required. Objective: The study aimed to report the current status and summarize the expert opinion on laparoscopic donor hepatectomy. Methods: An expert consensus meeting was held on September 8, 2016, in Seoul, Korea. Results: Laparoscopic donor left lateral sectionectomy could be considered the standard practice in pediatric LDLT. In adult LDLT, laparoscopy-assisted donor hepatectomy or left hepatectomy is potentially the next need, requiring more evidence for becoming standard practice. Laparoscopic donor right hepatectomy is still in the developmental stage, and more supporting evidence is required. Waving the cost consideration, the robotic approach could be a valid alternative for the suitable approaches of laparoscopy. Conclusions: Laparoscopic donor hepatectomy is increasing its role in both pediatric and adult LDLT. However, for major donor hepatectomy, more evidence is needed.

Major concerns about donor safety cause controversy and limit the use of living donor liver transplantation to overcome organ shortages. The Korean Organ Transplantation Registry established a nationwide organ transplantation registration system in 2014. We reviewed the prospectively collected data of all 832 living liver donors who underwent procedures between April 2014 and December 2015. We allocated the donors to a left lobe group (n = 59) and a right lobe group (n = 773) and analyzed the relations between graft types and remaining liver volumes and complications (graded using the Clavien 5-tier grading system). The median follow-up was 19 months (range, 10-31 months). During the study period, 553 men and 279 women donated livers, and there were no deaths after living liver donation. The overall, biliary, and major complication (grade ≥ III) rates were 9.3%, 1.7%, and 1.9%, respectively. The graft types and remaining liver volume were associated with significantly different overall, biliary, and major complication rates. Of the 16 patients with major complications, 9 (56.3%) involved biliary complications (2 biliary strictures [12.5%] and 7 bile leakages [43.8%]). Among the 832 donors, the mean aspartate transaminase, alanine aminotransferase, and total bilirubin levels were 23.9 ± 8.1 IU/L, 20.9 ± 11.3 IU/L, and 0.8 ± 0.4 mg/dL, respectively, 6 months after liver donation. In conclusion, biliary complications were the most common types of major morbidity in living liver donors. Donor hepatectomy can be performed successfully with minimal and easily controlled complications. Our study shows that prospective, nationwide cohort data provide an important means of investigating the safety in living liver donation. Liver Transplantation 23 999-1006 2017 AASLD.

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.

Pure laparoscopic donor right hepatectomy (PLDRH) is not a standard procedure for living donor liver transplantation but is safe and reproducible in the hands of experienced surgeons. However, the perioperative outcomes of PLDRH have not been fully evaluated yet. We used propensity score matching to compare the perioperative complications and postoperative short-term outcomes of donors undergoing PLDRH and open donor right hepatectomy (ODRH). A total of 325 consecutive donors who underwent elective, adult-to-adult right hepatectomy were initially screened. After propensity score matching, all patients were divided into two groups: PLDRH (n = 123) and ODRH (n = 123) groups. Perioperative complications and postoperative outcomes were compared between the two groups. Postoperative pulmonary complications were significantly more common in the ODRH than in the PLDRH group (54.5 vs. 31.7%, P P = 0.167). Overall, surgical complication rates were similar between the two groups (P = 0.730). The opioid requirement during the first 7 postoperative days was higher in the ODRH group (686 vs. 568 mg, P P = 0.003 and P

BACKGROUND While portal flow (PF) plays an important role in determining graft outcomes in living donor liver transplantation, its impact in deceased donor liver transplantation (DDLT) is unclear. The aim of this study was to investigate the correlations between graft PF and graft outcomes in DDLT. METHODS We retrospectively investigated 1001 patients who underwent DDLT between January 2007 and June 2017 at our institution. The patients were divided into 3 groups according to hazard ratio for 1-year graft loss at each PF value, which was standardized with graft weight. Graft and recipient outcomes were compared between the groups. RESULTS The low-PF group (PF < 65 mL/min/100 g, n = 210, P = 0.011) and the high-PF group (PF ≥ 155 mL/min/100 g, n = 159, P = 0.018) showed significantly poorer 1-year graft survival compared with the intermediate-PF group (PF ≥ 65 mL/min/100 g and < 155 mL/min/100 g, n = 632). The patients in the low-PF group had severe reperfusion injury and were more frequently complicated with primary nonfunction (P = 0.013) and early allograft dysfunction (P < 0.001) compared with the other groups. In contrast, the patients in the high-PF group had milder reperfusion injury, but had lower intraoperative hepatic artery flow with higher incidence of hepatic artery thrombosis (P = 0.043) and biliary complication (P = 0.041) compared with the other groups. CONCLUSIONS These results suggest that intraoperative PF plays an important role in determining early graft outcomes after DDLT.

Lecture With the accumulation of experience in both living donor liver transplantation (LDLT) and laparoscopic liver surgery, efforts have been made to minimize the surgical trauma to the donor and many institutions are now using minimally invasive approach for donor surgery. Nevertheless, the overwhelming majority of the grafts used for adult LDLT are right lobe grafts. Right lobe, which usually consist of 2/3 of the liver, provides a larger size grafts, facilitating the recovery of the recipient but this comes at the price of the increase risk of the donor. It is known that utilization of right lobe has a higher complication and mortality rate compared to the left, but the utilization of the left lobe has not been practiced widely. In this talk, I'll provide the early results of our program using laparoscopic approach for left lobe and describe the detailed techniques through video presentation.

Objective Muscle depletion in patients undergoing liver transplantation affects the recipients' prognosis and therefore cannot be overlooked. We aimed to evaluate whether changes in muscle and fat mass during the preoperative period are associated with prognosis after deceased donor liver transplantation (DDLT). Materials and Methods This study included 72 patients who underwent DDLT and serial computed tomography (CT) scans. Skeletal muscle index (SMI) and fat mass index (FMI) were calculated using the muscle and fat area in CT performed 1 year prior to surgery (1 yr Pre-LT), just before surgery (Pre-LT), and after transplantation (Post-LT). Simple aspects of serial changes in muscle and fat mass were analyzed during three measurement time points. The rate of preoperative changes in body composition parameters were calculated (preoperative ΔSMI [%] = [SMI at Pre-LT − SMI at 1 yr Pre-LT] / SMI at Pre-LT × 100; preoperative ΔFMI [%] = [FMI at Pre-LT − FMI at 1 yr Pre-LT] / FMI at Pre-LT × 100) and assessed for correlation with patient survival. Results SMI significantly decreased during the preoperative period (mean preoperative ΔSMI, −13.04%, p < 0.001). In the multivariable analysis, preoperative ΔSMI (p = 0.016) and model for end-stage liver disease score (p = 0.011) were independent prognostic factors for overall survival. The mean survival time for patients with a threshold decrease in the preoperative ΔSMI (≤ −30%) was significantly shorter than for other patients (p = 0.007). Preoperative ΔFMI was not a prognostic factor but FMI increased during the postoperative period (p = 0.009) in all patients. Conclusion A large reduction in preoperative SMI was significantly associated with reduced survival after DDLT. Therefore, changes in muscle mass during the preoperative period can be considered as a prognostic factor for survival after DDLT.

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/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.

Background The incidence and etiology of hepatocellular carcinoma (HCC) vary widely according to race and geographic regions. The insertional mutagenesis of adeno-associated virus 2 (AAV2) has recently been considered a new viral etiology of HCC. The aim of this study was to investigate the frequency and clinical characteristics of AAV2 in Korean patients with HCC. Methods A total of 289 unrelated Korean patients with HCC, including 159 Hepatitis-B-related cases, 16 Hepatitis-C-related cases, and 114 viral serology-negative cases, who underwent surgery at the Samsung Medical Center in Korea from 2009 to 2014 were enrolled in this study. The presence of AAV2 in fresh-frozen tumor tissues was investigated by DNA PCR and Sanger sequencing. The clinical and pathological characteristics of AAV2-associated HCC in these patients were compared with previous findings in French patients. Results The AAV2 detection rate in Korean patients (2/289) was very low compared with that in French patients (11/193). Similar to the French patients, the Korean patients with AAV2-related HCC showed no signs of liver cirrhosis. The Korean patients were younger than the French patients with the same AAV2-associated HCC; the ages at diagnosis of the two Korean patients were 47 and 39 yr, while the median age of the 11 French patients was 55 yr (range 43-90 yr). Conclusions AAV2-associated HCC was very rare in Korean patients with HCC. Despite a limited number of cases, this study is the first to report the clinical characteristics of Korean patients with AAV2-associated HCC. These findings suggest epidemiologic differences in viral hepatocarcinogenesis between Korean and European patients.

Purpose: The factors related to early-onset tumor recurrence in patients with spontaneously ruptured hepatocellular carcinoma (HCC) after hepatectomy remain unclear. The aims of the present study were to compare characteristics between early and late recurrence groups in spontaneously ruptured HCC patients who received curative hepatectomy and to identify risk factors for mortality. Methods: We selected 19 patients who had been diagnosed with spontaneously ruptured HCC and who were treated with curative liver resection between 1998 and 2013. The 19 patients were divided into 2 groups: the early recurrence group of patients who experienced tumor recurrence within 12 months after hepatectomy, and the late recurrence group of patients who experienced recurrence after 12 months or who did not experience recurrence. Results: The median tumor size was 7.4 cm, and there were no cases of postoperative mortality. Patient survival rates at 1, 3, and 5 years were 78.9%, 58.6%, and 58.6%, respectively. The incidence of tumor protrusion in the early recurrence group was higher than that in the late recurrence group (100% vs. 30%, respectively, P = 0.003). There were no statistically significant differences in other factors between the 2 groups. Multivariate analysis showed that greater than 30% protrusion of the tumor was a predictor of patient survival. Conclusion: The results from the present study suggests that spontaneously ruptured HCC patients with protrusion should be frequently monitored after hepatectomy in order to achieve early detection of tumor recurrence and improve survival.

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.

Simplifying the therapeutic regimen of liver transplantation (LT) recipients may help prevent acute rejection and graft failure. The present study aimed to evaluate the efficacy and safety of conversion from twice-daily tacrolimus to once-daily extended-release tacrolimus under concurrent mycophenolate mofetil therapy in stable LT recipients. This randomized, prospective, controlled study included 91 patients who underwent LTs with at least 1 year of posttransplant follow-up. Conversion was made on a 1 mg to 1 mg basis. No incidences of biopsy-proven acute rejection, graft failure, or death were reported in either group at 24 weeks. Median serum tacrolimus level of the study group was 20% less than that of the control group at 8 weeks. However, no significant differences regarding biochemical indicators of liver function or serum creatinine levels were observed between the 2 groups. Adverse event (AE) profiles were similar for both groups, with comparable incidences of AEs and serious AEs. No significant differences regarding efficacy or safety were observed between the once-daily tacrolimus and twice-daily tacrolimus groups of stable LT recipients. In conclusion, our study suggests that tacrolimus can be safely converted from a twice-daily regimen to a once-daily regimen in stable LT recipients.

Cytochrome P450 (CYP) 3A5 polymorphism influences tacrolimus metabolism, but its effect on the drug pharmacokinetics in liver transplant recipients switched to once-daily extended-release formulation remains unknown. The aim of this study is to analyze the effect of CYP3A5 polymorphism on liver function after once-daily tacrolimus conversion in liver transplant patients. A prospective open-label study included 60 stable liver transplant recipients who underwent 1:1 conversion from twice-daily tacrolimus to once-daily tacrolimus. All participants were genotyped for CYP3A5 polymorphism. The study was registered at ClinicalTrials.gov (NCT 02882113). Twenty-eight patients were enrolled in the CYP3A5 expressor group and 32 in the non-expressor group. Although there was no statistical difference, incidence of liver dysfunction was higher in the expressor group than in the non-expressor group when converted to once-daily extended-release tacrolimus (p = 0.088). No biopsy-proven acute rejection, graft failure, and mortality were observed in either group. The decrease in dose-adjusted trough level (&minus, 42.9% vs. &minus, 26.1%) and dose/kg-adjusted trough level of tacrolimus (&minus, 40.0% vs. &minus, 23.7%) was significantly greater in the expressor group than in the non-expressors after the conversion. A pharmacokinetic analysis was performed in 10 patients and tacrolimus absorption in the non-expressor group was slower than in the expressor group. In line with this observation, the area under the curve for once-daily tacrolimus correlated with trough level (Cmin) in the non-expressors and peak concentration (Cmax) in the expressors. CYP3A5 genotyping in liver transplant recipients leads to prediction of pharmacokinetics after switching from a twice-daily regimen to a once-daily dosage form, which makes it possible to establish an appropriate dose of tacrolimus.