The first successful report of liver transplantation from category III donation after circulatory death in South Korea: a case report

Deceased donor liver transplantation (DDLT) using donations after brain death (DBDs) has been widely performed in Korea. However, to date, there is no report regarding donation after circulatory death (DCD) category III. A 56-year-old male patient diagnosed with hepatitis B virus-associated liver cirrhosis underwent DDLT using DCD category III. The recipient's recovery was uneventful, and he was discharged on postoperative day 37. Currently, the patient is alive, with no complications 20 months after transplantation. This case suggests that DCD with LT is both feasible and safe. Further studies are required to validate this finding.ope

A comparative study of postoperative outcomes between minimally invasive living donor hepatectomy and open living donor hepatectomy: The Korean organ transplantation registry

Background: This study evaluated the safety and effectiveness of minimally invasive living donor hepatectomy in comparison with the open procedure, using Korean Organ Transplantation Registry data. Methods: We reviewed the prospectively collected data of all 1,694 living liver donors (1,071 men, 623 women) who underwent donor hepatectomy between April 2014 and December 2017. The donors were grouped on the basis of procedure type to the minimally invasive procedure group (n = 304) or to the open procedure group (n = 1,390) and analyzed the relationships between clinical data and complications. Results: No donors died after the procedure. The overall complication rates after operation in the minimally invasive procedure group and the open procedure group were 6.2% and 3.5%, respectively. Biliary complications were the most frequent events in both groups (minimally invasive procedure group, 2.4%; open procedure group, 1.6%). The majority of complications occurred within 7 days after surgery in both groups. The duration of hospitalization was shorter in the minimally invasive procedure group than in the open procedure group (9.04 ± 3.78 days versus 10.29 ± 4.01 days; P < .05). Conclusion: Based on its similar outcomes in our study, minimally invasive donor hepatectomy cannot be an alternative option compared with the open procedure method. To overcome this, we need to ensure better surgical safety, such as lower complication rate and shorter duration of hospitalization.ope

Invasive fungal infection in liver transplant recipients in a prophylactic era: A multicenter retrospective cohort study in Korea

The epidemiology of invasive fungal infections (IFIs) after liver transplantation (LT) is continuing to evolve in the current era of antifungal prophylactic therapy. This multicenter retrospective cohort study aimed to evaluate the epidemiology, risk factors, and outcomes of IFIs among LT recipients in the current era.We analyzed a total of 482 LT recipients aged 18 years and older who were admitted to 3 tertiary hospitals in Korea between January 2009 and February 2012.Twenty-four episodes of IFIs occurred in 23 patients (4.77%; 23/482). Of these episodes, 20 were proven cases and 4 were probable cases according to EORTC/MSG criteria. Among these cases, IFI developed within 30 days of transplantation in 47.8% of recipients, from 31 to 180 days in 34.8% of recipients, and from 181 to 365 days in 17.4% of recipients. The most common isolates were Candida species (n = 12, 52.2%; Candida albicans, 6 cases; Candida tropicalis, 1 case; Candida glabrata, 1 case; Candida parapsilosis, 1 case; and unspecified Candida species, 1 case) and Aspergillus species (n = 7, 30.4%). The mortality in patients with IFIs was significantly higher than that in patients without IFIs (47.83% [11/23] vs 7.18% [33/459], P < .001). The incidence of late-onset IFIs is increasing in the antifungal prophylactic era, and fluconazole-resistant non-albicans Candida species have not yet emerged in Korea.ope

Impact of everolimus on survival after liver transplantation for hepatocellular carcinoma

Background/aims: This study aimed to investigate whether everolimus (EVR) affects long-term survival after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Methods: The data from 303 consecutive patients with HCC who had undergone LT from January 2012 to July 2018 were retrospectively reviewed. The patients were divided into two groups: 1) patients treated with EVR in combination with calcineurin inhibitors (CNIs) (EVR group; n=114) and 2) patients treated with CNI-based therapy without EVR (non-EVR group; n=189). Time to recurrence (TTR) and overall survival (OS) after propensity score (PS) matching were compared between the groups, and prognostic factors for TTR and OS were evaluated. Results: The EVR group exhibited more aggressive tumor biology than the non-EVR group, such as a higher number of tumors (P=0.003), a higher prevalence of microscopic vascular invasion (P=0.017) and exceeding Milan criteria (P=0.029). Compared with the PS-matched non-EVR group, the PS-matched EVR group had significantly better TTR (P<0.001) and OS (P<0.001). In multivariable analysis, EVR was identified as an independent prognostic factor for TTR (hazard ratio [HR], 0.248; P=0.001) and OS (HR, 0.145; P<0.001). Conclusion: Combined with CNIs, EVR has the potential to prolong long-term survival in patients undergoing LT for HCC. These findings warrant further investigation in a well-designed prospective study.ope

New-onset diabetes after adult liver transplantation in the Korean Organ Transplantation Registry (KOTRY) study

Background: New-onset diabetes after transplantation (NODAT) is a serious complication following liver transplantation (LT). The present study aimed to investigate the incidence of and risk factors for NODAT using the Korean Organ Transplantation Registry (KOTRY) database. Methods: Patients with history of pediatric transplantation (age ≤18 years), re-transplantation, multi-organ transplantation, or pre-existing diabetes mellitus were excluded. A total of 1,919 non-diabetic adult patients who underwent a primary LT between May 2014 and December 2017 were included. Risk factors were identified using Cox regression analysis. Results: NODAT occurred in 19.7% (n=377) of adult liver transplant recipients. Multivariate analysis showed steroid use, increased age, and high body mass index (BMI) in recipients, and implantation of a left-side liver graft was closely associated with NODAT in adult LT. In living donor liver transplant (LDLT) patients (n=1,473), open donor hepatectomy in the living donors, steroid use, small for size liver graft (graft to recipient weight ratio ≤0.8), increased age, and high BMI in the recipient were predictive factors for NODAT. The use of antimetabolite and basiliximab induction reduced the incidence of NODAT in adult LT and in adult LDLT. Conclusions: Basiliximab induction, early steroid withdrawal, and antimetabolite therapy may prevent NODAT after adult LT. High BMI or advanced age in liver recipients, open donor hepatectomy in living donors, and small size liver graft can predict the occurrence of NODAT after adult LT or LDLT.ope

Hepatitis B Prophylaxis after Liver Transplantation in Korea: Analysis of the KOTRY Database

Background: Prophylaxis for hepatitis B virus (HBV) recurrence is essential after liver transplantation (LT) in HBV-associated recipients. We conducted real-world analysis of HBV prophylaxis after LT in the Korean population. Methods: Korean Organ Transplantation Registry (KOTRY) database and additionally collected data (n = 326) were analyzed with special reference to types of HBV prophylaxis. Results: The study cohort comprised 267 cases of living-donor LT and 59 cases of deceased-donor LT. Hepatocellular carcinoma (HCC) was diagnosed in 232 (71.2%) of these subjects. Antiviral agents were used in 255 patients (78.2%) prior to LT. HBV DNA was undetectable in 69 cases (21.2%) and detectable over wide concentrations in the other 257 patients (78.8%) prior to LT. Polymerase chain reaction analysis of the store blood samples detected HBV DNA in all patients, with 159 patients (48.9%) showing concentrations > 100 IU/mL. Post-transplant HBV regimens during the first year included combination therapy in 196 (60.1%), hepatitis B immunoglobulin (HBIG) monotherapy in 121 (37.1%), and antiviral monotherapy in 9 (2.8%). In the second post-transplant year, these regimens had changed to combination therapy in 187 (57.4%), HBIG monotherapy in 112 (34.4%), and antiviral monotherapy in 27 (8.3%). Trough antibody to hepatitis B surface antigen titers > 500 IU/mL and >1,000 IU/mL were observed in 61.7% and 25.2%, respectively. The mean simulative half-life of HBIG was 21.6 +/- 4.3 days with a median 17.7 days. Up to 2-year follow-up period, HCC recurrence and HBV recurrence developed in 18 (5.5%) and 6 (1.8%), respectively. HCC recurrence developed in 3 of 6 patients with HBV recurrence. Conclusion: Combination therapy is the mainstay of HBV prophylaxis protocols in a majority of Korean LT centers, but HBIG was often administered excessively. Individualized optimization of HBIG treatments using SHL is necessary to adjust the HBIG infusion interval.ope

Efficacy and safety of prolonged-release versus immediate-release tacrolimus in de novo liver transplant recipients in South Korea: a randomized open-label phase 4 study (MAPLE)

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.ope

Non-Renal Risk Factors for Chronic Kidney Disease in Liver Recipients with Functionally Intact Kidneys at 1 Month

Chronic kidney disease (CKD) is a critical complication of liver transplants, of which non-renal risk factors are not fully understood yet. This study aimed to reveal pre- and post-transplant risk factors for CKD (&lt;60 mL/min/1.73 m2), examining liver recipients with functionally intact kidneys one month after grafting using nationwide cohort data. Baseline risk factors were analyzed with multivariable Cox regression analyses and post-transplant risk factors were investigated with the time-dependent Cox model and matched analyses of time-conditional propensity scores. Of the 2274 recipients with a one-month eGFR ≥ 60 mL/min/1.73 m2, 494 (22.3%) developed CKD during a mean follow-up of 36.6 ± 14.4 months. Age, female sex, lower body mass index, pre-transplant diabetes mellitus, and lower performance status emerged as baseline risk factors for CKD. Time-dependent Cox analyses revealed that recurrent hepatocellular carcinoma (HR = 1.93, 95% CI 1.06-3.53) and infection (HR = 1.44, 95% CI 1.12-1.60) were significant post-transplant risk factors for CKD. Patients who experienced one of those factors showed a significantly higher risk of subsequent CKD compared with the matched controls who lacked these features (p = 0.013 for recurrent hepatocellular carcinoma, and p = 0.003 for infection, respectively). This study clarifies pre- and post-transplant non-renal risk factors, which lead to renal impairment after LT independently from patients' renal functional reserve.ope

The feasibility of organ transplantation during the COVID-19 outbreak: experiences from South Korea

Background: The coronavirus disease 2019 (COVID-19) has forced healthcare systems to reduce transplant activities in order to preserve resources and minimize the risk of nosocomial transmission. Although transplantation societies around the world have proposed interim recommendations, little is known about the safety of transplant surgery under pandemic conditions and how transplant medicine should move forward after the peak of the pandemic. Methods: We describe our experiences regarding the continuation of living and deceased donor transplantation under infection control measures during the COVID-19 outbreak in South Korea. We reviewed consecutive liver and kidney transplantations at Severance Hospital and analyzed national transplantation activities in South Korea. Results: Transplantation activities with living and deceased donors remained stable during the COVID-19 outbreak compared to the same period in 2019. We performed 94 transplantations (58 kidney, 35 liver, and 1 simultaneous liver-kidney) during the COVID-19 outbreak. Twenty-five patients underwent desensitization therapy prior to transplant (nine ABO-incompatible kidney, eight human leukocyte antigen-incompatible kidney, and eight ABO-incompatible liver). No transplant recipients in our center contracted COVID-19. In South Korea, national transplant activities with living and deceased donors remained stable in 2020 compared to 2019. Conclusions: Organ transplantation during pandemics appears to be feasible with appropriate infection prevention measures.ope

Islet Encapsulation Using Chondrocyte

Diabetes mellitus is one of the leading metabolic diseases that cause an increasing rate of mortality and morbidity. Recently, rather than the current drug treatment, pancreatic islet transplantation has been regarded as a potentially promising strategy for insulin- dependent diabetes mellitus while preventing complications such as kidney damage, vascular damage, nerve damage, and blindness. Recently, a number of advanced islet encapsulation techniques have been designed to enhance the efficiency of islet transplantation, including cell sheet engineering and generation of 3D islet spheroids by high density suspension system (HDSS). Chondrocytes derived from cartilage sources have been used as an encapsulation biomaterial for islets not only for autograft but also for allograft and xenograft transplantation. Cartilage is an avascular, white connective tissue that is rich in extracellular matrix, and expandable in vitro. Hence, this tissue might have immunologically privileged properties that make it an intelligent cell source for manufacture of encapsulation biomaterials. However, cell sheet engineering and HDSS still have their respective limitations, which need to be elucidated. This review will describe the advantages and disadvantages of the current encapsulation techniques in order to provide a comprehensive foundation for further modifications and improvements of tissue engineering for islet transplantation.ope