Review Article

Advances and challenges in pediatric liver transplantation: Global perspectives and the Japanese experience

Mureo Kasahara¹ , Seisuke Sakamoto¹ , Hideki Ohdan²

Ann Liver Transplant 2024; 4(2): 42-46

Abstract  

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Abstract : Pediatric organ transplantation has evolved significantly since the 1950s, with breakthroughs in immunosuppressive therapy in the 1980s. Worldwide, around 2,700 pediatric liver transplants are performed annually, with living donor transplants dominating in Japan due to cultural and legal limitations surrounding brain-dead organ donation. Regional disparities in transplant practices are evident, with brain-dead transplants being more common in North America and Europe, while living donor transplants prevail in Asia and the Middle East. Technological innovations such as machine perfusion and minimally invasive surgery have enhanced transplant outcomes and addressed the ongoing donor shortage. Despite excellent long-term survival rates, challenges persist, particularly with graft fibrosis, which affects over 60% of pediatric recipients within a decade post-transplant. A critical issue is the transition of pediatric transplant patients to adult care facilities, where nonadherence with immunosuppressive regimens is associated with a high mortality rate. As the number of pediatric transplant cases rises, the need for increased human and financial support becomes more pressing to ensure these patients receive comprehensive care throughout their lives.

Original Article

Graft-versus-host disease in liver transplantation: Experience in the Korean single center

Hwa-Hee Koh , Deok-Gie Kim , Minyu Kang , Eun-Ki Min , Jae Geun Lee , Dong Jin Joo , Myoung Soo Kim

Ann Liver Transplant 2024; 4(2): 56-62

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Abstract : Background: This investigation delves into the intricacies of graft-versus-host disease (GVHD) in the context of liver transplantation (LT), focusing on the experiences from a Korean single center. Despite GVHD’s relatively low incidence, its severe implications on patient mortality underscore the urgent need for advanced management and comprehension strategies. Methods: In a retrospective analysis at Severance Hospital, Korea, we reviewed 1,107 adult LT recipients from January 2009 to March 2023, excluding those who succumbed within 14 days post-transplantation, to scrutinize the manifestation, treatment, and outcomes of GVHD. Diagnostic approaches ranged from skin to colonoscopic biopsies, with interventions including high-dose corticosteroids and tailored immunosuppressive adjustments. Results: GVHD was diagnosed in 1.3% of the study cohort, predominantly identified through skin biopsies. Critical findings include the significant role of donor liver characteristics and recipient pre-transplant conditions in GVHD development. Notably, GVHD affected patients exhibited markedly lower survival rates at one year compared to their non-GVHD controls (21.4% vs. 90.2%, p

Original Article

Outcomes of emergency pediatric ABO-incompatible living donor liver transplantation in Korea

Sunghyo An¹ , Jongman Kim¹ , Sang Jin Kim^2,3 , Soon-Young Kim⁴ , Jung-Bun Park⁴ , Youngwon Hwang⁴ , Dong-Hwan Jung⁵

Ann Liver Transplant 2024; 4(2): 63-70

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Abstract : Background: Emergency pediatric living donor liver transplantation (LDLT) is vital for acute liver failure patients in life-threatening situations. However, we do not know the outcomes of emergency pediatric ABO-incompatible (ABOi)-LDLT, which is an alternative treatment for patients without ABO-compatible (ABOc) living liver donors. The purpose of our study is to compare the outcomes between emergency pediatric ABOi-LDLT and emergency pediatric ABOc-LDLT using data from the Korean Network for Organ Sharing (KONOS). Methods: We analyzed retrospective KONOS data for consecutive pediatric emergency LDLT patients between 2017 and 2021 in Korea. Results: The incidence of ABOc-LDLT and ABOi-LDLT was 83% (n=44) and 17% (n=9), respectively. The baseline, pre-transplant care, postoperative complications, and infectious complications of ABOi-LDLT did not differ from those of ABOc-LDLT. Graft survival and overall survival at 5 years in ABOi-LDLT were 100% and 100%, respectively, which was better than in ABOc-LDLT, but the survival difference between the two groups was not significant. No developed acute rejection in ABOi-LDLT patients. No factors in the multivariate analysis were related to patient mortality or graft failure. Neither graft failure nor death was associated with ABOi-LDLT. Conclusion: This study concludes that emergency pediatric ABOi-LDLT is safe and feasible for use in ALF patients as well as other urgent instances.

Original Article

Chronological improvements of living donor liver transplantation for hepatocellular carcinoma in Seoul National University Hospital

Saran Ochir Gongor¹ , Kwang-Woong Lee^1,2 , Nam-Joon Yi^1,2 , YoungRok Choi^1,2 , Suk Kyun Hong^1,2 , Jeong-Moo Lee² , Jae-Yoon Kim² , Kyung-Suk Suh^1,2

Ann Liver Transplant 2024; 4(2): 71-79

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Abstract : Background: Challenging clinical circumstances and high demand for liver transplantation have led to a refinement in the recipient selection criteria. This study aims to investigate the hypothesis that surgical outcomes in living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC) have improved over time with the shift from morphological to biological criteria. Methods: A retrospective analysis was conducted on 942 adult HCC patients underwent LDLT at Seoul National University Hospital between 2000 and 2022. Study populations were divided into Group A (2000.01.01–2011.06.30, n=314) and Group B (2011.07.01–2022.06.30, n=628). Baseline characteristics, perioperative factors, and survival outcomes were compared. Results: Group B demonstrated higher recurrence-free survival (RFS) compared to Group A (p=0.03). Additionally, Group B exhibited superior overall survival rates at the 1-, 3-, and 5-year intervals (95.9%, 87.9%, 84.6%, p

Original Article

Validation of risk factors for graft-to-recipient weight ratio less than 0.8 graft in living donor liver transplantation with single center data

Young Jin Yoo , Minyu Kang , Hwa-Hee Koh , Eun-Ki Min , Jae Geun Lee , Myoung Soo Kim , Dong Jin Joo , Deok-Gie Kim

Ann Liver Transplant 2024; 4(2): 80-85

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Abstract : Background: The use of small grafts, defined by a graft-to-recipient weight ratio (GRWR) less than 0.8, is possibly associated with an increased risk of graft loss in living donor liver transplantation (LDLT). This study aims to validate risk factors for graft loss in LDLT with GRWR

Original Article

Donor safety in living donors with a body mass index of ≥30 kg/m²: Experience of high-volume center in Asia

Sung-Min Kim , Young-In Yoon , Deok-Bog Moon , Ki-Hun Kim , Chul-Soo Ahn , Tae-Yong Ha , Gi-Won Song , Dong-Hwan Jung , Gil-Chun Park , Shin Hwang , Sung-Gyu Lee

Ann Liver Transplant 2024; 4(2): 86-94

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Abstract : Background: As the prevalence of obesity and nonalcoholic fatty liver disease increases in recent years, the number of living donor liver transplantation from donor with high body mass index (BMI) is increasing. However, data on the effect of high BMI on outcomes in liver donors are lacking. This study aimed to investigate the influence of donor obesity (BMI ≥30 kg/m²) on and clinical outcomes after donor right liver resection (DRLR). Methods: Records of all living donors who underwent DRLR between January 2015 and December 2020 at Asan Medical Center were retrospectively reviewed. We divided donors into obese (BMI ≥30 kg/m², n=41) and normal-weight (BMI ≤25 kg/m², n=1,125) groups. To eliminate bias, matching was performed using the greedy method, and 34 donors involved in this study in each group. Results: After matching, preoperatively, the obese group had significantly higher preoperative levels of serum aspartate aminotransferase (p=0.021), alanine aminotransferase (p=0.003), and a larger celiac artery depth ratio (p

Original Article

Varied strategies for alcohol-related liver transplants in South Korea

Hyun Hwa Choi^1,2 , Kwang-Woong Lee² , Bong-Wan Kim³ , Dong-Sik Kim⁴ , Gyu-Seong Choi⁵ , Hae Won Lee⁶ , Ho Joong Choi⁷ , Jaryung Han⁸ , Je Ho Ryu⁹ , Kwan Woo Kim¹⁰ , Man Ki Ju¹¹ , Min-Su Park¹² , Myoung Soo Kim¹³ , Seok-Hwan Kim¹⁴ , Seoung Hoon Kim¹⁵ , Shin Hwang¹⁶ , Sung Won Jung¹⁷ , Tae-Seok Kim¹⁸ , Woo Young Shin¹⁹

Ann Liver Transplant 2024; 4(2): 95-101

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Abstract : Backgrounds: Alcohol-related liver disease (ALD) is currently a major indication for liver transplantation (LT) in South Korea. Alcoholic recidivism is a primary concern after LT for ALD. However, it is unclear how patients who have received LT for ALD are managed regarding medical and psychological issues. Furthermore, management approaches vary across centers. This study aims to investigate how these management approaches differ among centers. Methods: We conducted a survey of 19 liver transplant centers in South Korea to gather detailed information on the management protocols and related issues of ALD in LT patients. Results: All 19 centers that responded to the survey had been performing LT for patients with ALD for more than 5 years. Nine out of the 19 centers (47%) stated that a minimum abstinence period of 1–6 months from alcohol was required before evaluating LT and enrolling on the transplant waiting list. Only 2 (10%) and 5 (26%) centers had protocols for assessing alcohol consumption while awaiting LT or for treating alcohol consumption after transplantation, respectively. Monitoring abstinence from drinking before and after LT mostly relied on direct interviews, and alcohol biomarkers were not used. Conclusion: Our findings emphasize the importance of consistent patient management guidelines for ALD-LTs in South Korea.

Original Article

Outcomes of living donor liver transplantation in patients with concurrent extrahepatic malignancy

John Hee Park , Jongman Kim , Sunghyo An , Namkee Oh , Jinsoo Rhu , Gyu-Seong Choi , Jae-Won Joh

Ann Liver Transplant 2024; 4(2): 102-107

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Abstract : Background: Concurrently extrahepatic malignancy (EHM) has long been considered a relative contraindication to liver transplantation because of cancer recurrence. However, we were frequently challenged as living donor liver transplantation (LDLT) may be the only life-saving option available in the setting of end-stage liver disease, or hepatocellular carcinoma (HCC) with concurrent EHM. In this study, we aim to analyze the outcome of adult LDLT with concurrent EHM at the time of LDLT. Methods: Of 2,448 adults who underwent LDLT from May 1996 to January 2023 at our institution, we retrospectively analyzed data for 16 patients with an EHM treated within 6 months at the time of LDLT. Results: Among 16 patients, one patient died of postoperative liver failure, and another died 3 months post-surgery due to bowel perforation. The cumulative overall survival rates at 1-year, 3-year, and 5-year were 87.5%, 78.8%, and 68.9%, respectively. Five patients died during follow-up; only one patient died due to a cancer-related cause. None of the eight patients with low-risk EHM showed EHM recurrence after LDLT. EHM recurrence occurred in one patient with intermediate risk, and cancer progression was seen in one patient with high-risk EHM. Concurrent HCC was present in six patients, and HCC recurrence occurred in two (33.33%). There was no statistically significant difference in survival between patients with hematologic (n=5) and non-hematologic (n=11) EHM (p=0.891). Conclusion: Our study shows a high survival rate for LDLT in patients with concurrently EHM. Hence, we suggest that concurrent EHM should not be a contraindication to LDLT even when ‘minimum remission times’ have not yet elapsed.

Case Report

Pre-operative sodium benzoate can rapid increase sodium level and induce central pontine myelinolysis after liver transplantation: Case report

Luka Jashi^1,3 , Kwang-Woong Lee^1,2 , Nam-Joon Yi^1,2 , YoungRok Choi^1,2 , Jae-Yoon Kim¹ , Suk-Kyun Hong^1,2 , Kyung-Suk Suh^1,2

Ann Liver Transplant 2024; 4(2): 108-111

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Abstract : Central pontine myelinolysis (CPM) is a severe neurological complication observed after liver transplantation (LT), with a mortality rate exceeding 50%. This study presents a case report of a 43-year-old female patient with alcoholic liver cirrhosis who underwent liver transplantation and subsequently developed CPM. The patient admitted with symptoms and signs of acute on chronic liver failure, such as hyponatremia, and hepatic encephalopathy Grade 3 Glasgow Coma Scale (GCS) 10. Sodium benzoate was started together with lactulose. Ammonia level was decreased and mentality was also improved. However, sodium level was increased up to 160 mmol/L. After liver transplantation, the patient become drowsier (GCS 6–9) even with good liver function. The brain magnetic resonance imaging at the post-LT 5th day showed CPM. The mentality was slowly improved after conservative management with low level of tacrolimus. This case gives a lesson that pre-operative sodium benzoate treatment can increase the risk of CPM by increasing sodium level in patients with severe hyponatremia. Therefore, careful monitoring of sodium level is important when sodium benzoate is prescribed.

Case Report

Deceased donor liver transplantation for post-hepatectomy liver failure with fixed pupils

Sunghyo An¹ , Jongman Kim¹ , Sungjun Jo¹ , Namkee Oh¹ , Eunmi Gil^1,2 , Gaabsoo Kim³

Ann Liver Transplant 2024; 4(2): 112-116

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Abstract : Deceased donor liver transplantation (DDLT) raises ethical and social questions about liver transplantation for patients who are not expected to live. Patients with post-hepatectomy liver failure must have DDLT as soon as possible. Here, we detail a particular dilemma that the transplant team had while deciding whether to harvest liver from a deceased donor in the face of the recipient’s non-reactive, fully dilated pupils while they awaited a liver transplant in the intensive care unit. Despite having fixed dilated pupils during the neurologic evaluation, the patient eventually had effective DDLT, indicating that DDLT should not be done unless there is obvious brain death.

Case Report

Lacticaseibacillus rhamnosus infection in an immunocompromised liver transplant recipient and review of literature

Ahneez Abdul Hameed¹ , Bindu Mulakavalupil² , Francesca Trovato² , Anita Verma¹

Ann Liver Transplant 2024; 4(2): 117-123

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Abstract : Lacticaseibacillus rhamnosus (L. rhamnosus), known for its beneficial effects on gut and vaginal microflora, is considered a low-pathogenicity organism with the propensity to cause infection in immunocompromised patients. To our knowledge, no cases have been reported in liver transplant recipients (LTR). Here, we report the first case with L. rhamnosus intra-abdominal infection and pleural empyema in a LTR, along with review of the literature. The isolate found in peritoneal and pleural fluid cultures exhibited complete resistance to routinely prescribed antibiotics in LTR. The majority of infections documented in the literature occur in individuals with chronic health conditions, and are linked to high mortality rates. In conclusion, while L. rhamnosus is an opportunistic pathogen, this and previous documented examples underscore the need of heightened recognition of its potential as a pathogen, and its resistance in immunocompromised patients. In order to get a more favourable result, it is crucial to initiate tailored early antimicrobial therapy alongside efficient source control.

Case Report

Successful living liver donation from a septuagenarian donor with cardiac diseases

Jiyoung Baik¹ , Jongman Kim¹ , Eunjin Lee¹ , Sunghyo An¹ , Namkee Oh¹ , Eunmi Gil^1,2 , Gaabsoo Kim³

Ann Liver Transplant 2024; 4(2): 124-128

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Abstract : We present the case of a 74-year-old female who had a right hepatectomy performed laparoscopically to donate her liver to her a 40-year-old son who had alcoholic liver cirrhosis. She voluntarily cooperated, and thorough medical and psychological evaluations were carried out. The receiver underwent surgery in 296 minutes, while the donor took 158 minutes. With normal liver function, the donor and recipient were released from the hospital on days 10 and 14, respectively, after a smooth recovery. Three months following the living donor liver transplant, both the receiver and the living liver donor have not experienced any problems and are doing well.

Case Report

Two cases of living donor liver transplantation for colorectal liver metastases in Korea

Abdullah Alshamrani , Eunjin Lee , Youngju Rhu , Sunghyo An , Sungjun Jo , Namkee Oh , Jinsoo Rhu , Jongman Kim

Ann Liver Transplant 2024; 4(2): 129-133

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Abstract : Colorectal cancer (CRC) poses a significant global health challenge, particularly with patients often experiencing liver metastases. Surgical resection remains the standard treatment; however, many patients face ineligibility due to disease status, contributing to poor prognoses. Liver transplantation (LT) is a viable alternative for select patients with advanced disease. This case report details the clinical outcomes of two CRC patients with multiple liver metastases who successfully underwent living donor LT (LDLT). Both individuals had intricate medical histories and pre-existing liver issues. Patient 1, a 58-year-old male, received extensive pre-transplant interventions, including multiple radiofrequency ablations and pulmonary resections. Patient 2, a 50-year-old male, had cirrhosis alongside colorectal cancer with liver metastases and completed chemotherapy. The cases illustrate LDLT's viability and potential advantages for complex CRC cases with liver metastases. The patients’ intricate medical backgrounds necessitate thorough pre-transplant evaluations and vigilant post-transplant supervision. Moreover, these cases highlight the critical nature of ongoing follow-up for evaluating long-term survival and recognizing possible complications.

Case Report

Portal vein interposition in living donor liver transplantation for a pediatric patient with hepatoblastoma invading the portal vein

Jung-Man Namgoong¹ , Shin Hwang¹ , Gil-Chun Park¹ , Hyunhee Kwon¹ , Suhyeon Ha¹ , Sujin Gang¹ , Jueun Park¹ , Kyung Mo Kim² , Seak Hee Oh²

Ann Liver Transplant 2024; 4(2): 134-140

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Abstract : Liver transplantation is accepted as an effective therapeutic option for unresectable hepatoblastoma. We present a pediatric case of hepatoblastoma patient with portal vein (PV) tumor thrombosis (PVTT) that occluded the main PV completely despite aggressive neoadjuvant chemotherapy. The patient was a 4-year and 2-month-old 17-kg boy suffering from hepatoblastoma with PVTT, which was partially regressed by neoadjuvant chemotherapy. Viable PVTT remained after right trisectionectomy and repetition of systemic chemotherapy. To remove the tumor completely, we performed living donor liver transplantation (LDLT) using his father’s left liver graft. The native PV was completely occluded with PVTT and abundant pericholedochal collaterals developed. The native PV was meticulously dissected to fully expose the superior mesenteric vein-splenic vein confluence. This confluence portion was deeply clamped and opened to use as a viable PV inflow source. A cold-stored fresh external iliac vein homograft was anastomosed to the confluence portion as an end-to-end fashion and passed through the native retropancreatic PV tract after mechanical dilatation of the tract. Left liver graft implantation was performed using standard procedures of pediatric LDLT. The patient recovered uneventfully. He will undergo scheduled adjuvant chemotherapy. Customized design for PV reconstruction using interposition vein graft with viable PV inflow source can result in successful PV reconstruction with complete removal of PVTT.