• Molecules and Cells
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• 제46권11호
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• pp.688-699
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• 2023

We set up this study to understand the underlying mechanisms of reduced ceramides on immune cells in acute rejection (AR). The concentrations of ceramides and sphingomyelins were measured in the sera from hepatic transplant patients, skin graft mice and hepatocyte transplant mice by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Serum concentrations of C24 ceramide, C24:1 ceramide, C16:0 sphingomyelin, and C18:1 sphingomyelin were lower in liver transplantation (LT) recipients with than without AR. Comparisons with the results of LT patients with infection and cardiac transplant patients with cardiac allograft vasculopathy in humans and in mouse skin graft and hepatocyte transplant models suggested that the reduced C24 and C24:1 ceramides were specifically involved in AR. A ceramide synthase inhibitor, fumonisin B₁ exacerbated allogeneic immune responses in vitro and in vivo, and reduced tolerogenic dendritic cells (tDCs), while increased P3-like plasmacytoid DCs (pDCs) in the draining lymph nodes from allogeneic skin graft mice. The results of mixed lymphocyte reactions with ceranib-2, an inhibitor of ceramidase, and C24 ceramide also support that increasing ceramide concentrations could benefit transplant recipients with AR. The results suggest increasing ceramides as novel therapeutic target for AR, where reduced ceramides were associated with the changes in DC subsets, in particular tDCs.

• Korean Journal of Radiology
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• 제23권1호
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• pp.52-59
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• 2022

Objective: To investigate whether the diagnostic performance of CT angiography (CTA) could be improved by modifying the conventional criterion (anastomosis site abnormality) to diagnose hepatic artery occlusion (HAO) after liver transplantation (LT) in suspected patients with Doppler ultrasound (US) abnormalities. Materials and Methods: One hundred thirty-four adult LT recipients (88 males and 46 females; mean age, 52.7 years) with suspected HAO on Doppler US (40 HAO and 94 non-HAO according to the reference standards) were included. We evaluated 1) abnormalities in the HA anastomosis, categorized as a cutoff, ≥ 50% stenosis at the anastomotic site, or diffuse stenosis at both graft and recipient sides around the anastomosis, and 2) abnormalities in the distal run-off, including invisibility or irregular, faint, and discontinuous enhancement. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the conventional (considering anastomosis site abnormalities alone) and modified CTA criteria (abnormalities in both the anastomosis site and distal run-off) for the diagnosis of HAO were calculated and compared using the McNemar test. Results: By using the conventional criterion to diagnose HAO, the sensitivity, specificity, PPV, NPV, and accuracy were 100% (40/40), 74.5% (70/94), 62.5% (40/64), 100% (70/70), and 82.1% (110/134), respectively. The modified criterion for diagnosing HAO showed significantly increased specificity (93.6%, 88/94) and accuracy (93.3%, 125/134) compared to that with the conventional criterion (p = 0.001 and 0.002, respectively), although the sensitivity (92.5%, 37/40) decreased slightly without statistical significance (p = 0.250). Conclusion: The modified criterion considering abnormalities in both the anastomosis site and distal run-off improved the diagnostic performance of CTA for HAO in suspected patients with Doppler US abnormalities, particularly by increasing the specificity.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제20권3호
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• pp.178-185
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• 2017

Purpose: To evaluate the outcomes of a hybrid prophylactic strategy to prevent cytomegalovirus (CMV) disease in pediatric liver transplantation (LT) patients. Methods: CMV DNAemia was regularly monitored by quantitative nucleic acid amplification test (QNAT) and was quantified in all children. CMV infection and disease were defined according to the International Consensus Guidelines. The hybrid strategy against CMV infection consisted of universal 3-week prophylaxis and preemptive treatment of intravenous ganciclovir regardless of the recipient's serostatus. Results: A total of 143 children who underwent living donor LT were managed using the hybrid strategy. The overall incidence of CMV infection by QNAT was 48.3% (n=69/143). The highest CMV DNAemia positivity was observed in 49.2% (n=60/122) of children in the D+/R+ group, followed by 46.7% (n=7/15) in the D+/R- group. CMV disease was noted in 26.1% (n=18/69) patients. Forty-three (62.3%) children had undergone preemptive therapy consisting of intravenous ganciclovir. No symptomatic patients developed tissue-invasive disease, resulting in no CMV-associated mortality. Conclusion: The incidence of CMV infection was high in pediatric LT patients despite the hybrid strategy. However, tissue-invasive disease in pediatric LT did not occur.

• 한국임상약학회지
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• 제28권1호
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• pp.57-64
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• 2018

Background: Patients experience significant differences in aspects of mortality, quality of life, and costs between during the year of receiving liver transplant (LT) and the subsequent years (post-LT). This study aimed to estimate the medical utilization and cost of LT for patients compared to post-LT patients by using a recent National Patient Sample (NPS) data provided by the Korean Health Insurance Review and Assessment Service (HIRA). Methods: This study used a subset of the 2015 HIRA-NPS. Patient claims data that included Z944 (Korean Standard Classification of Diseases code for LT status) were selected. Within the selected data, LT patients were identified based on whether the national health insurance number code of Q80 (procedure code for LT surgery) was included, and they were compared to post-LT patients. Results: In the analysis, 330 patients were included. The average cost per patient was $90,066{\pm}36,959$ thousand KRW and $10,557{\pm}9,668$ thousand KRW for LT and post-LT patients, respectively. Especially, LT patients' costs for injection/procedure, surgery/treatment, and examination were higher than other costs, being $35,983{\pm}18,115$ thousand KRW, $28,246{\pm}9,408$ thousand KRW, and $12,131{\pm}6,604$ thousand KRW, respectively. For inpatients, the average number of hospitalized days was $63.5{\pm}66.0$ days for LT patients and $22.3{\pm}35.1$ days for post-LT patients. Conclusion: Compared to post-LT patients, LT patients had higher costs, especially for injection/procedure, surgery/treatment, and examination. Additionally, the LT group had longer hospitalization duration and higher costs for their hospital admission, whereas they did not show a significant difference in number of visits and medical costs for outpatient-care.

• Journal of Korean Medical Science
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• 제33권51호
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• pp.324.1-324.6
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• 2018

Oxysterol $7{\alpha}$-hydroxylase deficiency is a very rare liver disease categorized as inborn errors of bile acid synthesis, caused by CYP7B1 mutations. As it may cause rapid progression to end-stage liver disease even in early infancy, a high index of suspicion is required to prevent fatal outcomes. We describe the case of a 3-month-old boy with progressive cholestatic hepatitis and severe hepatic fibrosis. After excluding other etiologies for his early liver failure, we found that he had profuse urinary excretion of $3{\beta}$-monohydroxy-${\Delta}^5$-bile acid derivatives by gas chromatography/mass spectrometry analysis with dried urine spots on filter paper. He was confirmed to have a compound heterozygous mutation (p.Arg388Ter and p.Tyr469IlefsX5) of the CYP7B1 gene. After undergoing liver transplantation (LT) from his mother at 4 months of age, his deteriorated liver function completely normalized, and he had normal growth and development until the current follow-up at 33 months of age. We report the first Korean case of oxysterol $7{\alpha}$-hydroxylase deficiency in the youngest infant reported to undergo successful living donor LT to date.

• Journal of Korean Medical Science
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• 제33권45호
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• pp.283.1-283.10
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• 2018

Background: The role of sorafenib in patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) has been rarely studied. The aim of this study was to evaluate the efficacy of sorafenib in post-LT era. Methods: Consecutive patients with post-transplant HCC recurrence not eligible to resection or locoregional therapy were included. Patients receiving best supportive care (BSC) until 2007 were compared with those treated by sorafenib thereafter. Results: Of a total of 65 patients, 20 patients received BSC and 45 received sorafenib. Clinical characteristics were similar between two groups except that sorafenib group received tacrolimus and mammalian target-of-rapamycin inhibitors more frequently than BSC group. Treatment with sorafenib conferred a survival advantage as compared with BSC for survival after recurrence (median, 14.2 vs. 6.8 months; P = 0.01). In multivariate analyses, high serum ${\alpha}$-fetoprotein level, synchronous intrahepatic recurrence and distant metastasis at the time of recurrence, and BSC were independently associated with poorer survival after recurrence. Sorafenib treatment was associated with better survival after recurrence as compared with BSC (hazard ratio, 0.25; 95% confidence interval, 0.10-0.62; P = 0.002). In addition, sorafenib group showed tolerable toxicity in the post-transplant setting. Conclusion: Sorafenib may be beneficial in patients with post-transplant HCC recurrence.

• 대한핵의학회지
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• 제36권6호
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• pp.368-380
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• 2002

목적: 원발성 간암의 치료를 위해 간이식이 시행되고 있으나, 8-54%의 환자에서는 이식 후 원격 전이로 인한 재발이 보고 되고 있다. 이 연구는 간이식 예정인 원발성 간암 환자들에서 고식적인 검사로 진단하지 못한 간외 전이 진단에 있어서 FDG-PET의 유용성을 평가하고자 시행되었다. 대상 및 방법: 2001년 8월 이후 본원에서 간이식을 계획하고 전신 FDG-PET을 시행한 환자 중, FDG-PET 검사 이전에 복부 초음파와 CT, 흉부 x선 검사와 CT, 골스캔 등의 고식적인 검사를 시행하여 전이의 증거가 없거나(n=22), 애매한 이상 소견이 있었던(n=4) 원발성 간암 환자 26명(남:여=23:3, 평균 나이 55.7세)을 조사하였다. FDG-PET에서 양성을 보인 결과는 조직검사나 임상적인 추적 검사로 전이 여부를 확인하였다. 결과: 고식적 검사에서 애매한 이상 소견이 있었던 환자 4명 중 3명의 6개 병변이 FDG-PET에서 국소 대사 항진을 보였고, 전이로 확인되어 간이식을 시행하지 않았다. 이 중 5 병변들은 의심되지 않았던 부위에서 새로 발견된 것이었다. 다른 1명은 PET에서 음성 소견으로 간이식을 시행하였다. 고식적인 검사에서 전이를 의심할 만한 소견이 없었던 22명 중에서는 5명의 환자에서 7개의 간외 국소 대사항진 병변들이 FDG-PET에서 발견되었는데, 이들중 1명은 2개의 전이 병변이 확인되어 간이식을 시행하지 않았다. 다른 4명의 환자들에서 보인 5개의 국소 대사항진 병변들은 양성병변으로 확인되었고 이 중 3명은 간이식을 시행하였다. 요약하면, FDG-PET으로 4명의 환자에서 고식적인 검사로 찾지 못하던 전이 병변을 찾아 불필요한 간이식을 피할 수 있었다. 모두 17명에서 간이식이 시행되었다. 간의 조직 검사 소견과 비교하였을 때 생존 원발성 간암을 진단하는 FDG-PET의 민감도는 55.6% (5/9)이었고, 특이도는 87.5% (7/8)이었다. 결론: FDG-PET 전신 스캔은 간이식 예정인 원발성 간암 환자들에서 이전에 시행한 고식적인 검사들로 진단하지 못한 전이 병소들을 추가로 진단하여 불필요한 간이식 수술을 줄이는데 기여할 수 있었다.

• Pediatric Infection and Vaccine
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• 제25권2호
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• pp.82-90
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• 2018

목적: 16년간단일기관에서시행된간이식후소아에서발생한세균감염합병증의빈도와특징을분석하기위해시행되었다. 방법: 2000년 1월부터 2015년 6월까지 서울대학교병원에서 간이식을 시행 받은 207명 소아 중 다장기 이식이나 2번 이상의 간이식을 시행 받은 18명을 제외한 189명이 연구에 포함되었다. 감염 증상과 더불어 병원체가 증명된 세균 감염 만을 대상으로 하여 감염성 질환의 종류 및 발생 시기 등을 조사하였다. 결과: 189명의 간이식 소아의 중간연령은 24개월(2개월-16세)이었으며, 수술 후 1년 간 추적 관찰 하였다. 총 87명(46.0%)에서 132건(0.7건/명)의 세균 감염이 발생하였다. 균혈증(n=39, 29.5%), 복막염(n=28, 21.2%), 요로감염(n=25, 18.9%), 폐렴(n=20,15.2%)의 순이었다. 그람양성균이 66건(50%), 그람음성균이 66건(50%)에서 확인되었다. 세균 감염은 이식 후 1개월 이내에 84건(63.6%), 1-6개월에 32건(24.2%), 6개월 이후에 16건(12.1%)으로 이식 초기에 유의하게 많았다(P<0.05). 가장 흔한 그람양성균은 Staphylococcus aureus (n=20, 15.2%) 와 Enterococcus species (n=20, 15.2%) 였으며, 그람음성균은 Klebsiella species (n=18, 13.6%), Enterobacter species (n=13, 9.8%), Escherichia coli (n=11, 8.3%) 순으로 많았다. 이 중 7명(41%)이 감염성 합병증으로 사망하였다(균혈증 4명, 복막염 1명, 폐렴 2명). 결론: 지난 16년 간 본 기관에서 소아에게 시행한 간이식 후 발생한 감염성 합병증의 빈도와 종류는 기존의 연구들과 비슷하였다. 간이식 후 소아에서 세균 감염 합병증은 이식 후 1개월 이내에 가장 많이 발생하며, 1개월이 지난 후에도 중증의 세균 감염으로 인한 사망률이 높아 6개월 전까지는 면밀한 세균 감염 합병증의 진단 및 치료가 필수적이다. 본 연구를 통해 향후 간이식의 예후 향상을 위한 연구의 토대가 될 것을 기대한다.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제6권1호
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• pp.32-38
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• 2003

목 적: HBcAb 양성인 공여자로부터 생체 부분 간이식을 시행할 때 HBsAg 음성인 수혜자가 B형 간염 바이러스에 감염될 가능성이 높다. 본 연구에서는 삼성서울병원의 소아 생체 부분 간이식에서 능동 면역을 주로 사용하였던 초창기와 Hepatitis Bimmunoglobulin (HBIg) 단독 요법을 사용하였던 후기를 비교 분석하여 간이식 후 de novo hepatitis B발생에 대한 HBIg 단독 요법의 예방 효과에 대해 조사해 보고자 하였다. 방 법: 1996년 5월부터 2002년 6월까지 시행한 생체 부분 간이식에서 공여자가 HBcAb 양성이었으며 수혜자가 HBsAg 음성인 소아는 15명이었다. 다른 이유로 사망한 2명을 제외한 13명 중 11명은 HBsAb 양성, 2명은 naive (HBsAb 음성, HBcAb 음성)였다. 모든 환자는 간이식 전 B형 간염 바이러스 예방 접종을 실시하였다. 초기 단계에는(1997년 1월~1997년 11월, 3명) 수혜자가 HBsAb 양성인 경우 간이식 후 B형 간염 추가접종을 실시하였다. 후기 단계에서는(1997년 12월 이후, 10명) 간이식 전후에 모두 B형 간염 예방 접종을 실시한 이후 항체 양성인 수혜자에게 HBsAb 항체가를 200 IU/L 이상 유지하기 위해 HBIg를 단독 유지요법으로 사용하였다. HBIg의 심한 부작용으로 인해 1명의 경우 Lamivudine을 사용하였다. De novo hepatitis B의 예방효과를 병력 고찰을 통하여 후향적으로 분석하였다. 결 과: 13명 중 3명(23.1%)에서 de novo hepatitis B가 발생하였다. 능동 면역만을 시행한 초기 단계에서 3명 중 3명 모두 7~19개월에 HBsAg 양성으로 혈청 변환을 하였다. 1명은 간이식 전 naive 혈청 소견이었고 2명은 HBsAb 양성인 상태였다. HBIg를 사용한 후기 단계에서는 10명 모두 관찰 기간 7~55개월 동안 HBsAg 음성으로 남아 있다. 결 론: HBIg 단독 요법은 HBcAb 양성인 공여자의 간을 이식받은 HBsAg 음성 수혜자에서 de novo hepatitis B를 예방하는데 효과적이다.

• Clinical and Experimental Pediatrics
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• 제60권3호
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• pp.86-93
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• 2017

Purpose: To evaluate the clinical spectrum of posttransplantation lymphoproliferative disorder (PTLD) after solid organ transplantation (SOT) in children. Methods: We retrospectively reviewed the medical records of 18 patients with PTLD who underwent liver (LT) or kidney transplantation (KT) between January 1995 and December 2014 in Seoul National University Children's Hospital. Results: Eighteen patients (3.9% of pediatric SOTs; LT:KT, 11:7; male to female, 9:9) were diagnosed as having PTLD over the last 2 decades (4.8% for LT and 2.9% for KT). PTLD usually presented with fever or gastrointestinal symptoms in a median period of 7 months after SOT. Eight cases had malignant lesions, and all the patients except one had evidence of Epstein-Barr virus (EBV) involvement, assessed by using in situ hybridization of tumor tissue or EBV viral load quantitation of blood. Remission was achieved in all patients with reduction of immunosuppression and/or rituximab therapy or chemotherapy, although 1 patient had allograft kidney loss and another died from complications of chemotherapy. The first case of PTLD was encountered after the introduction of tacrolimus for pediatric SOT in 2003. The recent increase in PTLD incidence in KT coincided with modification of clinical practice since 2012 to increase the tacrolimus trough level. Conclusion: While the outcome was favorable in that all patients achieved complete remission, some patients still had allograft loss or mortality. To prevent PTLD and improve its outcome, monitoring for EBV infection is essential, which would lead to appropriate modification of immunosuppression and enhanced surveillance for PTLD.