Targeted immune cell therapy for hepatocellular carcinoma using expanded liver mononuclear cell-derived natural killer cells.

Natural killer (NK) cells are a promising cellular therapy for T cell-refractory cancers but are frequently deficient or dysfunctional in patients with hepatocellular carcinoma (HCC). In the present study, we explored a novel therapy for HCC using NK cells derived from donor liver graft perfusate. These liver-derived NK cells, named LMNC-NK cells, are more abundant in liver mononuclear cells (LMNCs) than in peripheral blood mononuclear cells (PBMCs) from the same donor. We developed a method to expand LMNC-NK cells by 33.8±54.4-fold, enhancing their cytotoxic properties and cytokine production, including granzyme B, CD107a, TNF-α, and IFN-γ. These cells also showed an increased expression of cytotoxicity receptors. An RNA-seq analysis revealed considerable differences in gene expression between LMNC-NK and PBMC-NK cells, with 453 genes upregulated and 449 downregulated in LMNC-NK cells. These genes are involved in the mitogen-activated protein kinase cascade and cell differentiation, explaining the increased activity of LMNC-NK cells. Quantitative reverse transcription polymerase chain reaction confirmed the significant upregulation of TLR6, KIT, MMP14, IRF8, TCF7, FCERIG, LEF1, NLRp3, and IL16 in LMNC-NK cells. LMNC-NK cells effectively eliminated HepG-2-Luc cells in vitro, and in an orthotopic murine model of HCC, they exhibited a potent anti-tumor effect, outperforming PBMC-NK cells. The expression of the activation marker CD69+ in LMNC-NK cells was also significantly higher among tumor-infiltrating lymphocytes compared to PBMC-NK cells. Our research suggests that the adoptive transfer of LMNC-NK cells could be a promising treatment for HCC, offering a novel and effective source of NK cells with superior cytotoxic functions.

Optimal transplant strategy of pediatric liver transplantation for fibropolycystic liver disease: Multicenter retrospective study in Japan.

AIM: To assess the preoperative disease characteristics and indications for living donor liver transplantation (LDLT), complications, patient survival, and prognosis after LDLT for fibropolycystic liver disease (FLD) in children. METHODS: We undertook a cross-sectional survey of patients who underwent LDLT for FLD between January 2002 and December 2020. RESULTS: A total of 35 patients (22 male and 13 female individuals) with FLD were included in this study, of whom 19 (54.3%) had isolated congenital hepatic fibrosis and 16 (45.6%) had Caroli syndrome. Refractory gastrointestinal bleeding was the most frequent symptom related to the indication for LDLT, being found in 48.6% of our patients, followed by uncontrollable cholangitis and ascites. The median age at the time of LDLT was 8.1 years old. Of the 27 patients presenting with renal involvement, 13 patients required kidney transplantation (KT). Overall, the renal function after LDLT decreased regardless of renal involvement; however, patients with renal involvement had a significantly lower estimated glomerular filtration rate than those without renal involvement throughout the course of this study (p < 0.01). The 5-year overall patient survival rate was 97.1%. Two patients died with a median follow-up of 8.9 years after LDLT; one died due to sepsis 2 weeks after simultaneous liver-kidney transplantation and the other committed suicide 10 years after LDLT. CONCLUSION: The prognosis of the pediatric patients who underwent LDLT for FLD was excellent. However, an individualized treatment approach based on the status of the renal function and liver disease is important, as a certain proportion of patients require KT.

Liver transplantation for pediatric liver malignancies.

In the last few decades, collaboration between international pediatric oncology groups has resulted in significant improvement in survival after liver transplantation (LT) for pediatric liver tumors, and LT has become the accepted standard of care for unresectable pediatric liver tumors-either living donor liver transplantation or deceased donor liver transplantation. Hepatoblastoma and HCC are the common pediatric liver malignancies treated by LT, and LT is now the accepted treatment modality for unresectable nonmetastatic cases. The long-term survival rate is more than 80% in hepatoblastoma transplants. Furthermore, with the advent of living donor liver transplantation, the waitlist mortality, availability of a better graft quality with shorter ischemic times, and performance of LT with the appropriate timing between chemotherapy have all improved. Up to 80% of pediatric HCCs are unresectable, and studies have shown that LT for pediatric HCC has better outcomes than liver resection. Furthermore, LT has also shown better results than liver resection for cases of HCC not meeting Milan criteria. Given the rarity of pediatric liver malignancies and challenges in optimal management, a multidisciplinary treatment approach, research models building on what is already known, and consideration of newer treatment modalities are required for further improving the treatment of pediatric liver malignancies.

Daptomycin treatment for persistent bacteremia in a pediatric solid organ transplant recipient: Case report and literature review.

INTRODUCTION: Information on the clinical utility of daptomycin in patients with persistent bacteremia and daptomycin's pharmacokinetic data in pediatric patients has been sparse. In addition, reports on the experience of using daptomycin in children undergoing solid organ transplantation have been extremely limited. The authors describe a pediatric case of persistent bacteremia after solid organ transplantation successfully treated by daptomycin. Blood daptomycin concentrations were measured by liquid chromatography-mass spectrometry and pharmacokinetic analysis was performed. We also conducted a literature review on the use of daptomycin in children with persistent bacteremia. CASE REPORT: An eight-year-old girl who underwent small bowel and liver transplantation experienced persistent bacteremia due to Staphylococcus epidermidis. The bacteremia persisted despite standard therapy; however, it finally resolved with the addition of daptomycin. The patient had renal dysfunction and the initial dosing resulted in excessive drug exposure. The dosage was adjusted based on the pharmacokinetic analysis. The dosage of administrated teicoplanin was also adjusted according to trough concentration values. In the literature review, we identified 12 cases of neonates and 24 cases of post-neonatal children with the experience of using daptomycin for persistent bacteremia; however, no solid organ transplant recipient was identified. Similar trends in blood concentrations and dose ratios of teicoplanin and daptomycin were observed over time. DISCUSSION: More information is required regarding the clinical utility and pharmacokinetics of daptomycin in pediatric patients with persistent bacteremia. Referring to the exposure to renally excreted drugs that are routinely measured and pharmacokinetic analysis of daptomycin may be useful in optimizing the dose of daptomycin in special patient populations, including those with renal impairment.

Current Status and Outcomes of Living Donor Liver Transplantation for Pediatric Acute Liver Failure: Results From a Multicenter Retrospective Study Over Two Decades.

BACKGROUND: Although the outcomes of living donor liver transplantation (LDLT) for pediatric acute liver failure (PALF) have improved, patient survival remains lower than in patients with chronic liver disease. We investigated whether the poor outcomes of LDLT for PALF persisted in the contemporary transplant era. METHODS: We analyzed 193 patients who underwent LDLT between December 2000 and December 2020. The outcomes of patients managed in 2000-2010 (era 1) and 2011-2020 (era 2) were compared. RESULTS: The median age at the time of LDLT was 1.2 years both eras. An unknown etiology was the major cause in both groups. Patients in era 1 were more likely to have surgical complications, including hepatic artery and biliary complications (p = 0.001 and p = 0.013, respectively). The era had no impact on the infection rate after LDLT (cytomegalovirus, Epstein-Barr virus, and sepsis). The mortality rates of patients and grafts in era one were significantly higher (p = 0.03 and p = 0.047, respectively). The 1- and 5-year survival rates were 76.4% and 70.9%, respectively, in era 1, while they were 88.3% and 81.9% in era 2 (p = 0.042). Rejection was the most common cause of graft loss in both groups. In the multivariate analysis, sepsis during the 30 days after LDLT was independently associated with graft loss (p = 0.002). CONCLUSIONS: The survival of patients with PALF has improved in the contemporary transplant era. The early detection and proper management of rejection in patients, while being cautious of sepsis, should be recommended to improve outcomes further.

Long-Term Outcomes of Living Donor Liver Transplantation for Methylmalonic Acidemia.

BACKGROUND: Despite early diagnosis and medical interventions, patients with methylmalonic acidemia (MMA) suffer from multi-organ damage and recurrent metabolic decompensations. METHODS: We conducted the largest retrospective multi-center cohort study so far, involving five transplant centers (NCCHD, KUH, KUHP, ATAK, and EMC), and identified all MMA patients (n = 38) undergoing LDLT in the past two decades. Our primary outcome was patient survival, and secondary outcomes included death-censored graft survival and posttransplant complications. RESULTS: The overall 10-year patient survival and death-censored graft survival rates were 92% and 97%, respectively. Patients who underwent LDLT within 2 years of MMA onset showed significantly higher 10-year patient survival compared to those with an interval more than 2 years (100% vs. 81%, p = 0.038), although the death-censored graft survival were not statistically different (100% vs. 93%, p = 0.22). Over the long-term follow-up, 14 patients (37%) experienced intellectual disability, while two patients developed neurological complications, three patients experienced renal dysfunction, and one patient had biliary anastomotic stricture. The MMA level significantly decreased from 2218.5 mmol/L preoperative to 307.5 mmol/L postoperative (p = 0.038). CONCLUSIONS: LDLT achieves favorable long-term patient and graft survival outcomes for MMA patients. While not resulting in complete cure, our findings support the consideration of early LDLT within 2 years of disease onset. This approach holds the potential to mitigate recurrent metabolic decompensations, and preserve the long-term renal function.

Improved survival of pediatric deceased donor liver transplantation recipients after introduction of the pediatric prioritization system: Analysis of data from a Japanese national survey.

BACKGROUND: In Japan, there has never been a national analysis of pediatric deceased donor liver transplantation (pDDLT) based on donor and recipient factors. We constructed a Japanese nationwide database and assessed outcomes of pDDLT focusing on the pediatric prioritization system introduced in 2018. METHODS: We collected data on pDDLTs (<18 years) performed between 1999 and 2021 from the Japan Organ Transplant Network and Japanese Liver Transplantation Society, identified risk factors for graft survival and compared the characteristics and graft survival in pDDLTs conducted before and after the introduction of the pediatric prioritization system. RESULTS: Overall, 112 cases of pDDLT were included, with a 1-year graft survival rate of 86.6%. Four poor prognostic factors were identified: recipient intensive care unit stay, model for end-stage liver disease/pediatric end-stage liver disease score, donor cause of death, and donor total bilirubin. After the introduction of the system, allografts from pediatric donors were more reliably allocated to pediatric recipients and the annual number of pDDLTs increased. The 1-year graft survival rate improved significantly as did pDDLT conditions indicated by the risk factors. CONCLUSIONS: Under the revised allocation system, opportunities for pDDLT increased, resulting in favorable recipient and donor conditions and improved survival.

Japanese living donor liver transplantation criteria for hepatocellular carcinoma: nationwide cohort study.

BACKGROUND: Validating the expanded criteria for living donor liver transplantation for hepatocellular carcinoma using national data is highly significant. The aim of this study was to evaluate the validity of the new Japanese criteria for living donor liver transplantation for hepatocellular carcinoma patients and identify factors associated with a poor prognosis using the Japanese national data set. METHODS: The study population comprised patients who underwent living donor liver transplantation for hepatocellular carcinoma at 37 centres in Japan between 2010 and 2018. In a nationwide survey, the overall survival and recurrence-free survival rates were evaluated based on the new Japanese criteria for applying the 5-5-500 rule when extending the indication beyond the Milan criteria. Prognostic factors within the Japanese criteria were determined using the Cox proportional hazards model. RESULTS: Patients within (485 patients) and beyond (31 patients) the Japanese criteria exhibited 5-year overall survival rates of 81% and 58% and 5-year recurrence-free survival rates of 77% and 48% respectively. Patients who met the Milan criteria, but not the 5-5-500 rule, had poorer outcomes. Multivariate analysis for 474 patients identified a neutrophil-to-lymphocyte ratio greater than or equal to 5 and a history of hepatectomy as independent risk factors. CONCLUSION: This nationwide survey confirms the validity of the Japanese criteria. The poor prognostic factors within the Japanese criteria include a neutrophil-to-lymphocyte ratio greater than or equal to 5 and previous hepatectomy.

Impact of gallbladder hypoplasia on hilar hepatic ducts in biliary atresia.

BACKGROUND: Biliary atresia (BA) is an intractable disease of unknown cause that develops in the neonatal period. It causes jaundice and liver damage due to the destruction of extrahepatic biliary tracts,. We have found that heterozygous knockout mice of the SRY related HMG-box 17 (Sox17) gene, a master regulator of stem/progenitor cells in the gallbladder wall, exhibit a condition like BA. However, the precise contribution of hypoplastic gallbladder wall to the pathogenesis of hepatobiliary disease in Sox17 heterozygous embryos and human BA remains unclear. METHODS: We employed cholangiography and histological analyses in the mouse BA model. Furthermore, we conducted a retrospective analysis of human BA. RESULTS: We show that gallbladder wall hypoplasia causes abnormal multiple connections between the hilar hepatic bile ducts and the gallbladder-cystic duct in Sox17 heterozygous embryos. These multiple hilar extrahepatic ducts fuse with the developing intrahepatic duct walls and pull them out of the liver parenchyma, resulting in abnormal intrahepatic duct network and severe cholestasis. In human BA with gallbladder wall hypoplasia (i.e., abnormally reduced expression of SOX17), we also identify a strong association between reduced gallbladder width (a morphometric parameter indicating gallbladder wall hypoplasia) and severe liver injury at the time of the Kasai surgery, like the Sox17-mutant mouse model. CONCLUSIONS: Together with the close correlation between gallbladder wall hypoplasia and liver damage in both mouse and human cases, these findings provide an insight into the critical role of SOX17-positive gallbladder walls in establishing functional bile duct networks in the hepatic hilus of neonates.

Biliary atresia (BA) is a disease in newborns that causes a serious liver condition due to damage to the bile ducts (the pathways that carry bile juice). Although reduced function of a key gene called Sox17, which is essential for forming the gallbladder wall, has been observed in some BA cases, the link between gallbladder issues and liver damage is unknown. This study has shown how damage spreads through the bile ducts in the liver around the time of birth when there are problems in the gallbladder wall due to reduced SOX17 function. The findings indicate that proper growth of the gallbladder wall during this critical period is essential for forming a normal network of bile ducts in the developing liver. This discovery is promising for early diagnosis and better treatment of BA in newborns.

International multicenter study of ultralow graft-to-recipient weight ratio grafts in adult living donor liver transplantation.

Decreasing the graft size in living donor liver transplantation (LDLT) increases the risk of early allograft dysfunction. Graft-to-recipient weight ratio (GRWR) of 0.8 is considered the threshold. There is evidence that smaller volume grafts may also provide equally good outcomes, the cut-off of which remains unknown. In this retrospective multicenter study, 92 adult LDLTs with a final GRWR ≤0.6 performed at 12 international liver transplant centers over a 3-year period were included. Perioperative data including preoperative status, portal flow hemodynamics (PFH) and portal flow modulation, development of small for size syndrome (SFSS), morbidity, and mortality was collated and analyzed. Thirty-two (36.7%) patients developed SFSS and this was associated with increased 30-day, 90-day, and 1-year mortality. The preoperative model for end-stage liver disease and inpatient status were independent predictors for SFSS (P < .05). Pre-liver transplant renal dysfunction was an independent predictor of survival (hazard ratio 3.1; 95% confidence intervals 1.1, 8.9, P = .035). PFH or portal flow modulation were not predictive of SFSS or survival. We report the largest ever multicenter study of LDLT outcomes using ultralow GRWR grafts and for the first time validate the International Liver Transplantation Society-International Living donor liver transplantation study group-Liver Transplantation Society of India consensus definition and grading of SFSS. Preoperative recipient condition rather than GRWR and PFH were independent predictors of SFSS. Algorithms to predict SFSS and LT outcomes should incorporate recipient factors along with GRWR.

Impact of Portal Flow on the Prognosis of Children With Congenital Portosystemic Shunt: A Multicentric Observation Study in Japan.

BACKGROUND: Although congenital portosystemic shunts (CPSSs) are increasingly being recognized, the optimal treatment strategies and natural prognosis remain unclear, as individual CPSSs show different phenotypes. METHODS: The medical records of 122 patients who were diagnosed with CPSSs at 15 participating hospitals in Japan between 2000 and 2019 were collected for a retrospective analysis based on the state of portal vein (PV) visualization on imaging. RESULTS: Among the 122 patients, 75 (61.5%) showed PV on imaging. The median age at the diagnosis was 5 months. The main complications related to CPSS were hyperammonemia (85.2%), liver masses (25.4%), hepatopulmonary shunts (13.9%), and pulmonary hypertension (11.5%). The prevalence of complications was significantly higher in patients without PV visualization than in those with PV visualization (P < 0.001). Overall, 91 patients (74.6%) received treatment, including shunt closure by surgery or interventional radiology (n = 82) and liver transplantation (LT) or liver resection (n = 9). Over the past 20 years, there has been a decrease in the number of patients undergoing LT. Although most patients showed improvement or reduced progression of symptoms, liver masses and pulmonary hypertension were less likely to improve after shunt closure. Complications related to shunt closure were more likely to occur in patients without PV visualization (P = 0.001). In 25 patients (20.5%) without treatment, those without PV visualization were significantly more likely to develop complications related to CPSS than those with PV visualization (P = 0.011). CONCLUSION: Patients without PV visualization develop CPSS-related complications and, early treatment using prophylactic approaches should be considered, even if they are asymptomatic. LEVEL OF EVIDENCE: Level III.

Endoplasmic reticulum transporter OAT2 regulates drug metabolism and interaction.

Xenobiotic metabolic reactions in the hepatocyte endoplasmic reticulum (ER) including UDP-glucuronosyltransferase and carboxylesterase play central roles in the detoxification of medical agents with small- and medium-sized molecules. Although the catalytic sites of these enzymes exist inside of ER, the molecular mechanism for membrane permeation in the ER remains enigmatic. Here, we investigated that organic anion transporter 2 (OAT2) regulates the detoxification reactions of xenobiotic agents including anti-cancer capecitabine and antiviral zidovudine, via the permeation process across the ER membrane in the liver. Pharmacokinetic studies in patients with colorectal cancer revealed that the half-lives of capecitabine in rs2270860 (1324C > T) variants was 1.4 times higher than that in the C/C variants. Moreover, the hydrolysis of capecitabine to 5'-deoxy-5-fluorocytidine in primary cultured human hepatocytes was reduced by OAT2 inhibitor ketoprofen, whereas capecitabine hydrolysis directly assessed in human liver microsomes were not affected. The immunostaining of OAT2 was merged with ER marker calnexin in human liver periportal zone. These results suggested that OAT2 is involved in distribution of capecitabine into ER. Furthermore, we clarified that OAT2 plays an essential role in drug-drug interactions between zidovudine and valproic acid, leading to the alteration in zidovudine exposure to the body. Our findings contribute to mechanistically understanding medical agent detoxification, shedding light on the ER membrane permeation process as xenobiotic metabolic machinery to improve chemical changes in hydrophilic compounds.

Efficiency of machine perfusion in pediatric liver transplantation.

Liver transplantation is the only life-saving procedure for children with end-stage liver disease. The field is however heterogenic with various graft types, recipient age, weight, and underlying diseases. Despite recently improved overall outcomes and the expanded use of living donors, waiting list mortality remains unacceptable, particularly in small children and infants. Based on the known negative effects of elevated donor age, higher body mass index, and prolonged cold ischemia time, the number of available donors for pediatric recipients is limited. Machine perfusion has regained significant interest in the adult liver transplant population during the last decade. Ten randomized controlled trials are published with an overall advantage of machine perfusion techniques over cold storage regarding postoperative outcomes, including graft survival. The concept of hypothermic oxygenated perfusion (HOPE) was the first and only perfusion technique used for pediatric liver transplantation today. In 2018 the first pediatric candidate received a full-size graft donated after circulatory death with cold storage and HOPE, followed by a few split liver transplants after HOPE with an overall limited case number until today. One series of split procedures during HOPE was recently presented by colleagues from France with excellent results, reduced complications, and better graft survival. Such early experience paves the way for more systematic use of machine perfusion techniques for different graft types for pediatric recipients. Clinical reports of pediatric liver transplants with other perfusion techniques are awaited. Strong collaborative efforts are needed to explore the effect of perfusion techniques in this vulnerable population impacting not only the immediate posttransplant outcome but the development and success of an entire life.

Living-donor liver transplantation for methylmalonic acidemia patient with hepatocellular carcinoma: A case report and literature review.

BACKGROUND: Methylmalonic acidemia (MMA) is an autosomal recessive disorder caused by defects in propionyl-CoA (P-CoA) catabolism; of note, liver neoplasms rarely occur as a long-term complication of the disorder. Herein, we report the case of a patient with MMA and hepatocellular carcinoma (HCC) who was successfully treated with a living-donor liver transplant (LDLT) following prior kidney transplantation. CASE REPORT: A 25-year-old male patient with MMA underwent LDLT with a left lobe graft because of metabolic instability and liver neoplasms. He had presented with chronic symptoms of MMA, which had been diagnosed by genetic testing. Additionally, he had undergone living-donor kidney transplantation with his father as the donor due to end-stage kidney disease 6 years before the LDLT. He had an episode of metabolic decompensation triggered by coronavirus disease in 2019. Imaging studies revealed an intrahepatic neoplasm in the right hepatic lobe. Due to concerns about metabolic decompensation after hepatectomy, LDLT was performed using a left lobe graft obtained from the patient's mother. Pathological findings were consistent with the characteristics of well-to-moderately differentiated HCC. The postoperative course was uneventful, and the patient was discharged 48 days after the LDLT without any complications. At the 9-month follow-up, the patient's condition was satisfactory, with sufficient liver graft function and without metabolic decompensation. CONCLUSION: This case indicates that although HCC is a rare complication in patients with MMA, clinicians should be aware of hepatic malignancies during long-term follow-up.

"Reduced Size Liver Grafts in Pediatric Liver Transplantation; Technical Considerations".

Liver transplantation (LT) has become a vital treatment option for children with end-stage liver disease. Left lateral segment (LLS) grafts are particularly common in split and living donor LT for pediatric patients. However, challenges arise in small infants receiving LLS grafts, primarily due to graft-size mismatches, resulting in "large-for-size" grafts. To overcome this issue, the practice of further reducing grafts from the LLS to diminish graft thickness has been explored. Currently, the indication for reducing the thickness of LLS grafts includes recipients with a body weight (BW) under 5.0 kg, neonates with acute liver failure, or those with metabolic liver disease. At the National Center for Child Health and Development in Tokyo, Japan, among 131 recipients of reduced-size LLS grafts, a remarkable 15-year graft survival rate of 89.9% has been achieved in small infants. This success indicates that with experience and refinement of the technique, there's a trend towards improved graft survival in recipients with reduced-thickness LLS grafts. This advancement underscores the importance of BW-appropriate methods in graft selection to ensure exceptional outcomes in vulnerable pediatric patients in need of LT. These techniques' ongoing development and refinement are crucial in enhancing the survival rates and overall outcomes for these young patients.

Clinical symptoms, biochemistry, and liver histology during the native liver period of progressive familial intrahepatic cholestasis type 2.

BACKGROUND: Progressive familial intrahepatic cholestasis type 2 (PFIC2) is an ultra-rare disease caused by mutations in the ABCB11 gene. This study aimed to understand the course of PFIC2 during the native liver period. METHODS: From November 2014 to October 2015, a survey to identify PFIC2 patients was conducted in 207 hospitals registered with the Japanese Society of Pediatric Gastroenterology, Hepatology, and Nutrition. Investigators retrospectively collected clinical data at each facility in November 2018 using pre-specified forms. RESULTS: Based on the biallelic pathogenic variants in ABCB11 and/or no hepatic immunohistochemical detection of BSEP, 14 Japanese PFIC2 patients were enrolled at seven facilities. The median follow-up was 63.2 [47.7-123.3] months. The median age of disease onset was 2.5 [1-4] months. Twelve patients underwent living donor liver transplantation (LDLT), with a median age at LDLT of 9 [4-57] months. Two other patients received sodium 4-phenylbutyrate (NaPB) therapy and survived over 60 months with the native liver. No patients received biliary diversion. The cases that resulted in LDLT had gradually deteriorated growth retardation, biochemical tests, and liver histology since the initial visit. In the other two patients, jaundice, growth retardation, and most of the biochemical tests improved after NaPB therapy was started, but pruritus and liver fibrosis did not. CONCLUSIONS: Japanese PFIC2 patients had gradually worsening clinical findings since the initial visit, resulting in LDLT during infancy. NaPB therapy improved jaundice and growth retardation but was insufficient to treat pruritus and liver fibrosis.

Living donor liver transplantation on pediatric patient with Budd-Chiari syndrome: Case report and literature review.

INTRODUCTION: The management of Budd-Chiari syndrome is determined on the basis of the severity of the disease. There are no standard guidelines regarding the management of Budd-Chiari syndrome in children, particularly in cases of liver transplantation. Therefore, we present a case of a pediatric patient with Budd-Chiari syndrome treated with liver transplantation. CASE PRESENTATION: A female patient aged 1 year and 8 months presented to the hospital with an enlarged stomach in the last 1.5 months before admission. The patient was moderately ill, malnourished, and jaundiced. Liver biopsy revealed fibrosis in the portal area and confluent necrosis caused by vascular disorders. Magnetic resonance imaging (MRI) revealed a nutmeg liver and ascites due to the stenosis of the inferior vena cava at the level of the liver and the middle and left hepatic veins. The patient underwent living-donor liver transplantation. The occlusion of the proximal right hepatic vein due to the presence of a membrane was identified as the cause of Budd-Chiari syndrome in this case. Postoperatively, the patient's condition was stable and there was no sepsis or any other complications. CLINICAL DISCUSSION: Prothrombotic factors are often the underlying cause of more than 80 % of Budd-Chiari syndrome cases. Protein C deficiency is suspected to be a prothrombotic factor that triggers Budd-Chiari syndrome in patients. Liver transplantation is the treatment of choice for patients with Budd-Chiari syndrome who were not treated with anticoagulation therapy, angioplasty, and TIPS. CONCLUSION: Living-donor liver transplantation has a good outcome in the management of pediatric patients with Budd-Chiari syndrome.

Clinical outcomes after transplantation of domino grafts or standard deceased donor livers: a systematic review and meta-analysis.

BACKGROUND AND AIM: Domino liver transplantation (DLT) utilizes otherwise discarded livers as donor grafts for another recipients. It is unclear whether DLT has less favorable outcomes compared to deceased donor liver transplantation (DDLT). We aimed to assess the outcomes of DLT compared to DDLT. METHODS: MEDLINE, Embase, and Web of Science database were searched to identify studies comparing outcomes after DLT with DDLT. Data were pooled using random-effects modeling, evaluating odds ratios (OR) or mean difference (MD) for outcomes including waiting list time, severe hemorrhage, intensive care unit (ICU), length hospital stay (LOS), rejection, renal, vascular, and biliary events, and recipient survival at 1, 3, 5, and 10 years. RESULTS: Five studies were identified including 945 patients (DLT = 409, DDLT = 536). The DLT recipients were older compared to the DDLT group (P = 0.04), and both cohorts were comparable regarding lab MELD, hepatocellular carcinoma, and waitlist time. There were no differences in vascular (OR: 1.60, P = 0.39), renal (OR: 0.62, P = 0.24), biliary (OR: 1.51, P = 0.21), severe hemorrhage (OR: 1.09, P = 0.86), rejection (OR: 0.78, P = 0.51), ICU stay (MD: 0.50, P = 0.21), or LOS (MD: 1.68, P = 0.46) between DLT and DDLT. DLT and DDLT were associated with comparable 1-year (78.9% vs 80.4%; OR: 1.03, P = 0.89), 3-year (56.2% vs 54.1%; OR: 1.35, P = 0.07), and 10-year survival (6.5% vs 8.5%; OR: 0.8, P = 0.67) rates. DLT was associated with higher 5-year survival (41.6% vs 36.4%; OR: 1.70; P = 0.003) compared to DDLT, which was not confirmed at sensitivity analysis. CONCLUSION: This meta-analysis of the best available evidence (Level 2a) demonstrated that DLT and DDLT have comparable outcomes. As indications for liver transplantation expand, future high-quality research is encouraged to increase the DLT numbers in clinical practice, serving the growing waiting list candidates, with the caveat of uncertain de novo disease transmission risks.