Woo-Hyoung Kang

ABO-Incompatible Adult Living Donor Liver Transplantation Under the Desensitization Protocol With Rituximab

ABO incompatibility is no longer considered a contraindication for adult living donor liver transplantation (ALDLT) due to various strategies to overcome the ABO blood group barrier. We report the largest single‐center experience of ABO‐incompatible (ABOi) ALDLT in 235 adult patients. The desensitization protocol included a single dose of rituximab and total plasma exchange. In addition, local graft infusion therapy, cyclophosphamide, or splenectomy was used for a certain time period, but these treatments were eventually discontinued due to adverse events. There were three cases (1.3%) of in‐hospital mortality. The cumulative 3‐year graft and patient survival rates were 89.2% and 92.3%, respectively, and were comparable to those of the ABO‐compatible group (n = 1301). Despite promising survival outcomes, 17 patients (7.2%) experienced antibody‐mediated rejection that manifested as diffuse intrahepatic biliary stricture; six cases required retransplantation, and three patients died. ABOi ALDLT is a feasible method for expanding a living liver donor pool, but the efficacy of the desensitization protocol in targeting B cell immunity should be optimized.

Adult Living Donor Liver Transplantation for Acute-on-Chronic Liver Failure in High–Model for End-Stage Liver Disease Score Patients

The large volume of adult living donor liver transplantations (ALDLTs) at our center affords a unique opportunity to examine the impact of acute‐on‐chronic liver failure (ACLF) among high–Model for End‐Stage Liver Disease MELD score patients. From February 1998 to March 2010, 1958 cirrhotic recipients were analyzed to study the relationship between MELD scores and ALDLT outcomes. A total of 327 high‐MELD score recipients were categorized into ACLF and non‐ACLF groups, and their outcomes were compared. The 5‐year graft and patient survival in the high‐MELD group were 75.2% and 76.4%, respectively, which were significantly worse than the low and intermediate MELD groups. The presence of ACLF associated with higher MELD scores appeared to be the dominant factor responsible for the inferior results of patients with MELD score of 30–34 points. The 5‐year graft survivals in the ACLF group was 70.5% and in the non‐ACLF group it was 81.0% (p = 0.035). Therefore, ALDLT should be performed as soon as possible in high‐MELD score patients prior to ACLF development. Moreover, ACLF patients should be separately categorized when analyzing the outcomes of ALDLT. ALDLT for ACLF patients should not be discouraged because favorable outcomes can be expected through timely ALDLT and comprehensive management.

Preoperative prognostic values of α-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) in patients with hepatocellular carcinoma for living donor liver transplantation

BACKGROUND Adult living donor liver transplantation (LDLT) is one of the best treatments for hepatocellular carcinoma (HCC). However, when recurrence of HCC after LDLT occurs, the prognosis is poor because of rapid progression. Preoperative level of α-fetoprotein (AFP) and protein induced by vitamin K antagonist-II (PIVKA-II) reportedly correlate with recurrence of HCC after LDLT. METHODS We examined AFP and PIVKA-II preoperatively as predictors of HCC recurrence in 461 patients who underwent LDLT using right liver graft for HCC from May 2007 to December 2013. RESULTS Among these, 77 patients (16.7%) who experienced recurrence were retrospectively reviewed. Multivariate analysis revealed tumor size >5 cm, AFP >150 nag/mol and PIVKA-II >100 maul/mol as significant independent risk factors for recurrence. The median time to recurrence was 10 months. The median survival time after recurrence was 26 months, and the 1-, 3- and 5-year survival rates after recurrence were 80.5%, 58%, and 28.3% respectively. CONCLUSIONS Preoperatively, not only morphology of the tumor but also AFP and PIVKA-II levels can offers important information for the recurrence after LDLT for HCC. Thus, combination of tumor markers might be used for expansion of pre-existing strict selection criteria of liver transplantation for HCC.

Clinicopathological Features and Prognosis of Intrahepatic Cholangiocarcinoma After Liver Transplantation and Resection

BACKGROUND Intrahepatic cholangiocarcinoma (ICC) can be incidentally diagnosed after liver transplantation (LT). We investigated the clinicopathological features of LT recipients with ICC and compared prognosis with that of the control group. MATERIAL AND METHODS We identified 16 recipients with ICC in our institutional database. The propensity score-matched control group comprised 100 ICC patients who underwent hepatic resection (HR). RESULTS ICC incidence was 0.5% in all adult LT patients and 1.2% in adult recipients with primary liver cancer. Mean age was 58.0±4.8 years and 15 were male. All ICCs were diagnosed incidentally in the explanted livers. Mean ICC tumor diameter was 2.5±1.1 cm and 14 recipients had a single tumor. Tumor stages were I in 9, II in 5, and IV in 2. Concurrent second primary liver cancer was detected as hepatocellular carcinoma in 7 and combined hepatocellular carcinoma-cholangiocarcinoma in 1. Tumor recurrence and patient survival rates were 56.2% and 81.3% at 1 year and 78.1% and 52.4% at 5 years, respectively. Presence of second cancer did not affect tumor recurrence (p=0.959) or patient survival (p=0.737). All 3 patients with very early ICC did not show ICC recurrence. Compared with the control group, the tumor recurrence rate was higher after LT (p=0.024), but this difference disappeared after analysis was confined to recipients with ICC alone (p=0.121). Post-recurrence survival was not different after HR and LT (p=0.082). CONCLUSIONS ICC is rarely diagnosed after LT and half of such patients have second liver cancer. Post-transplant prognosis of ICC is poor except for very early ICC; thus, strict surveillance is mandatory.

Updated status of deceased-donor liver graft allocation for high-urgency adult patients in a Korean high-volume liver transplantation center.

BACKGROUND The number of deceased organ donors in Korea has been gradually increased to reach 8 per million population. This study intended to analyze the updated status of urgent deceased-donor liver transplantation in a Korean high-volume liver transplantation center. METHODS A retrospective study was performed with a 4-year study period from 2010 to 2013. RESULTS During the study period, 328 adult patients were enrolled at the Asan Medical Center for urgent orthotopic liver transplantation (OLT) with Korean Network for Organ Sharing status 1 in 56 (17.1%) and status 2A in 272 (82.9%). Of them, 201 (61.3%) were allocated for OLT and 195 (58.2%) actually underwent OLT after exclusion of 6 cases of spontaneous withdrawal. In KONOS status 1, liver grafts were initially allocated to 33 (58.9%), but 6 were withdrawn owing to clinical improvement, so 27 (48.2%) actually underwent OLT. In status 2A, 168 (61.8%) underwent OLT within 2 weeks of priority waiting period. According to ABO blood groups in recipients, the allocation probability was 68% (68 of 100) in group A, 60.6% (60 of 99) in group B, 64.1% (25 of 39) in group AB, and 53.3% (48 of 90) in group O. Mean waiting period for OLT was 5.7 ± 2.1 days. CONCLUSIONS Deceased donor incidence of ∼8 per million population contributed to meeting ∼60% of the demand for urgent deceased-donor liver transplantation in a Korean transplantation center, so further increasing deceased organ donor numbers is necessary to improve the current status of organ shortage.

Donor Safety and Recipient Liver Function After Right-Lobe Liver Transplantation From Living Donors With Gilbert Syndrome.

BACKGROUND Donor safety is the most important aspect in living-donor liver transplantation (LDLT). Gilbert syndrome is an autosomal recessive condition that is a common cause of isolated unconjugated hyperbilirubinemia, and its prevalence is not negligibly low in the general population. This study intended to assess donor safety and recipient liver function after LDLT with the use of right liver grafts from living donors with Gilbert syndrome. METHODS Among 2,140 right liver transplantations performed from January 2002 to December 20113 at our institution, we identified 12 living donors (0.6%) who showed a preoperative serum total bilirubin level of ≥2 mg/dL. These donors were clinically diagnosed with Gilbert syndrome. The clinical outcomes of these donors and their recipients were analyzed retrospectively. RESULTS The mean donor age was 24.6 ± 7.1 years, and 11 donors were male. All subjects met the preoperative evaluation conditions for right liver donation except for the level of unconjugated hyperbilirubinemia. The mean serum total bilirubin level of the donors was 2.23 ± 0.20 mg/dL before and 1.79 ± 0.61 mg/dL 1 year after right liver donation. The preoperative donor direct bilirubin level was 0.43 ± 0.19 mg/dL. The preoperative indocyanine green retention rate at 15 minutes was 8.2 ± 2.8%. All donors and recipients recovered uneventfully and were alive at the time of writing. The recipient serum total bilirubin level was 1.29 ± 0.47 mg/dL 1 year after LDLT. CONCLUSIONS We suggest that LDLT with living donors with Gilbert syndrome can be safely performed, but that a meticulous preoperative evaluation is vital to maximize donor safety.

Once-daily, prolonged-release tacrolimus vs twice-daily, immediate-release tacrolimus in de novo living-donor liver transplantation: A Phase 4, randomized, open-label, comparative, single-center study

Randomized, open‐label, comparative, single‐center, Phase 4, 24‐week study comparing pharmacokinetics (PK), safety, and efficacy of once‐daily, prolonged‐release tacrolimus (PR‐T) with twice‐daily, immediate‐release tacrolimus (IR‐T) in adult de novo living‐donor liver transplant (LDLT) recipients in Korea. All patients received intravenous tacrolimus from Day 0 (transplantation) for 4 days and were randomized (1:1) to receive oral PR‐T or IR‐T from Day 5. PK profiles were taken on Days 6 and 21. Primary endpoint: area under the concentration‐time curve over 24 hour (AUC0‐24). Predefined similarity interval for confidence intervals of ratios: 80%‐125%. Secondary endpoints included: tacrolimus concentration at 24 hour (C24), patient/graft survival, biopsy‐confirmed acute rejection (BCAR), treatment‐emergent adverse events (TEAEs). One‐hundred patients were included (PR‐T, n = 50; IR‐T, n = 50). Compared with IR‐T, 40% and 66% higher mean PR‐T daily doses resulted in similar AUC0‐24 between formulations on Day 6 (PR‐T:IR‐T ratio of means 96.8%), and numerically higher AUC0‐24 with PR‐T on Day 21 (128.8%), respectively. Linear relationship was similar between AUC0‐24 and C24, and formulations. No graft loss/deaths, incidence of BCAR and TEAEs similar between formulations. Higher PR‐T vs IR‐T doses were required to achieve comparable systemic exposure in Korean de novo LDLT recipients. PR‐T was efficacious; no new safety signals were detected.

Dual-graft adult living donor liver transplantation with ABO-incompatible graft: short-term and long-term outcomes

ABO‐incompatible (ABOi) dual‐graft (DG) adult living donor liver transplantation (ALDLT) is not commonly performed due to its inherently intricate surgical technique and immunological complexity. Therefore, data are lacking on the short‐ and long‐term clinical outcomes of ABOi DG ALDLT. We performed a retrospective study by reviewing the medical records of patients who underwent ABOi DG ALDLT between 2008 and 2014. Additionally, computed tomography volumetric analysis was conducted to assess the graft regeneration rate. The mean age of a total of 28 recipients was 50.2 ± 8.5 years, and the mean model for end‐stage liver disease score was 12.2 ± 4.6. The 1‐, 3‐, and 5‐year patient survival rate was 96.4% during the mean follow‐up period of 57.0 ± 22.4 months. The 1‐, 3‐, and 5‐year graft survival rate was 96.4%, 94.2%, and 92.0%, respectively, and no significant differences were observed between ABO‐compatible (ABOc) and ABOi grafts (P = .145). The biliary complication rate showed no significant difference (P = .195) between ABOc and ABOi grafts. Regeneration rates of ABOi grafts were not significantly different from those of ABOc grafts. DG ALDLT with ABOi and ABOc graft combination seems to be a feasible option for expanding the donor pool without additional donor risks.

In Situ Split Liver Transplantation for 2 Adult Recipients: A Single-Center Experience.

Background Split liver transplantation (SLT) for 2 adult patients by in situ splitting is rarely reported. This study analyzed the outcomes of SLT for 2 adult recipients at a single center. Material/Methods From 2003 to 2014, we performed 16 adult SLTs from 8 deceased donors using in situ splitting technique. We investigated the results of SLT and compared the outcomes of SLT with those of 393 cases of primary whole liver transplantation (WLT). Results All SLT donors were male. Eight recipients received right liver graft. Seven recipients received left liver graft. One recipient received dual-donor liver transplantation with 2 left-liver grafts (1 left liver graft from a living donor). The mean age of the recipients was 49.6±7 years. The Model for End-Stage Liver Disease (MELD) score of the recipients was 21.3±8.6. The mean cold ischemic time was 345.6±311.7 minutes. Graft and patient survival rates were 75.0% and 81.3%, respectively, at both 1 year and 5 years. There were 2 cases of biliary complication and 3 cases of vascular complication, but no incidence of arterial complication or small-for-size graft syndrome. The donor age of the SLT group was younger than that of the WLT group (p<0.001). The MELD score of the SLT group was lower than that of the WLT group (p=0.01). Patient and graft survival rates did not differ significantly between the SLT and WLT groups (p=0.47 and p=0.78, respectively). Conclusions In situ SLT for 2 adults is a feasible option to expand door pools in selected situations.

Successful introduction of Model for End-stage Liver Disease scoring in deceased donor liver transplantation in Korea: analysis of first 1 year experience at a high-volume transplantation center

Backgrounds/Aims Model for End-stage Liver Disease (MELD) score was adopted in June 2016 in Korea. Methods We analyzed changes in volumes and outcomes of deceased donor liver transplantation (DDLT) for 1 year before and after introduction of MELD scoring at Asan Medical Center. Results There were 64 cases of DDLT in 1 year before MELD introduction and 106 in 1 year after MELD introduction, an increase of 65%. The volume of DDLTs abruptly increased during first 3 months, but then returned to its usual level before MELD introduction, which indicated 3-month depletion of accumulated recipient pool with high MELD scores. The number of pediatric DDLT cases increased from 3 before MELD introduction to 11 after it, making up 21.4% and 47.8% of all cases of pediatric liver transplantation, respectively. The number of cases of retransplanted DDLTs increased from 4 to 27, representing 6.3% and 25.5% of all DDLT cases, respectively. The number of status 1 DDLT cases increased from 5 to 12, being 7.8% and 11.3% of all cases. Patient survival outcomes were similar before and after MELD introduction. Conclusions The number of DDLTs temporarily increased after adoption of MELD scoring due to accumulated recipient pool with high MELD scores. The numbers of retransplanted and pediatric DDLT cases significantly increased. Patient survival in adult and pediatric DDLT was comparable before and after adoption of MELD scoring. These results imply that Korean MELD score-based allocation system was successfully established within its first year.