Current status and future directions of liver transplantation for metabolic liver disease in children

Eldredge, Jessica A.; Hardikar, Winita

doi:10.1111/petr.14625

Cited by 3 publications

(3 citation statements)

References 128 publications

(362 reference statements)

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“…LT is the end solution for many liver diseases in children. The improved outcome of LT in children is dependent on many factors as innovative immunosuppression, skillful surgical techniques, and good pre-and post-operative management [7]. Timely diagnosis and treatment of postoperative complications have a significant impact on the successful outcome [8].…”

Section: Discussionmentioning

confidence: 99%

D-dimer Level Is Non-Specifically Elevated Post-Living-Related Liver Transplantation in Children

Darwish,

Adawy,

Saber

et al. 2024

IJG

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Background/Objective: D-dimer, a soluble fibrin degradation product, is used to be a marker of vascular thrombosis. However, it has been reported to be elevated in different pathological conditions other than thrombosis. Moreover, its pattern post-liver transplantation (LT) in children is not known. So, we aimed to report its pattern within the first-month post-LT in children and its level in different early post-LT complications. Methods: It is a retrospective observational cohort study in which 52 children who underwent living-related liver transplantation (LRLT) were included. All the available clinical, imaging, and laboratory data including D-dimer level were collected from the patients' files. Those who developed complications within the first post-LT month were assigned to the complication group (n=41), and others were assigned to the non-complication group (n=11). Results: D-dimer level pre-LT ranged from 0.12-16.41 mg/l, with no significant difference between the complication and non-complication groups. Postoperatively, the D-dimer levels were elevated and did not normalize till the postoperative day (POD) 30. The minimum reported level was 1.2 mg/l on POD0 while the maximum one was 33.12 mg/l on POD12. There were no significant differences between the complication and non-complication groups about the D-dimer level from the pre-LT day till the POD30 (p>0.05). The D-dimer level at the onset of the different complications showed no significant difference among the thrombotic, ACR, and the other complication subgroups (p=0.748). Moreover, the vascular thrombosis subgroup didn’t show a significant difference between the D-dimer level before- and at the onset of thrombosis (p=0.480). Conclusion: D-dimer is non-specifically elevated within the 1<sup>st</sup>-month post-LRLT in children with no clear trend. Moreover, it doesn’t normalize till the end of the 1<sup>st</sup> post-LT month. Being high early postoperatively doesn't necessarily indicate vascular thrombosis or other complications but rather the nature of the transplantation circumstances.

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Section: Discussionmentioning

confidence: 99%

D-dimer Level Is Non-Specifically Elevated Post-Living-Related Liver Transplantation in Children

Darwish,

Adawy,

Saber

et al. 2024

IJG

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“…Inborn errors of metabolism are the second most common indication for LTx in the pediatric population with an excellent survival outcome (>95% at one year, between 80% and 90% at 10 years). 74 In mitochondrial hepatopathies, LTx has been considered controversial due to unpredictable outcomes and ethical problems in allocating resources to children that might present extrahepatic involvement and/or possible neurological deterioration. A first preliminary study in a cohort of dGk deficient patients by Dimmock et al 75 in 2008 suggests a long-term survival in the absence of profound central hypotonia, significant psychomotor retardation or nystagmus but further case reports or series studies argue the benefit of LTx even in the presence of mild neurological symptoms.…”

Section: Discussionmentioning

confidence: 99%

Deoxyguanosine kinase deficiency: natural history and liver transplant outcome

Manzoni,

Carli,

Gaignard

et al. 2024

Brain Communications

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Autosomal recessive pathogenetic variants in the DGUOK gene cause deficiency of deoxyguanosine kinase activity and mitochondrial deoxynucleotides pool imbalance, consequently, leading to quantitative and/or qualitative impairment of mitochondrial DNA synthesis. Typically, patients present early-onset liver failure with or without neurological involvement and a clinical course rapidly progressing to death. This is an international multicentre study aiming to provide a retrospective natural history of deoxyguanosine kinase deficient patients. A systematic literature review from January 2001 to June 2023 was conducted. Physicians of research centers or clinicians all around the world caring for previously reported patients were contacted to provide follow-up information or additional clinical, biochemical, histological/histochemical, and molecular genetics data for unreported cases with a confirmed molecular diagnosis of deoxyguanosine kinase deficiency. A cohort of 202 genetically confirmed patients, 36 unreported, and 166 from a systematic literature review, were analyzed. Patients had a neonatal onset (≤ 1 month) in 55.7% of cases, infantile (>1 month and ≤ 1 year) in 32.3%, pediatric (>1 year and ≤18 years) in 2.5%, and adult (>18 years) in 9.5%. Kaplan-Meier analysis showed statistically different survival rates (p < 0.0001) among the four age groups with the highest mortality for neonatal onset. Based on the clinical phenotype, we defined four different clinical subtypes: hepatocerebral (58.8%), isolated hepatopathy (21.9%), hepatomyoencephalopathy (9.6%), and isolated myopathy (9.6%). Muscle involvement was predominant in adult-onset cases whereas liver dysfunction causes morbidity and mortality in early-onset patients with a median survival of less than 1 year. No genotype-phenotype correlation was identified. Liver transplant significantly modified the survival rate in 26 treated patients when compared with untreated. Only six patients had additional mild neurological signs after liver transplant. In conclusion, deoxyguanosine kinase deficiency is a disease spectrum with a prevalent liver and brain tissue-specificity in neonatal and infantile-onset patients and muscle tissue-specificity in adult-onset cases. Our study provides clinical, molecular genetics, and biochemical data for early diagnosis, clinical trial planning, and immediate intervention with liver transplant and/or nucleoside supplementation.

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“…

We read with great interest the recent article related to liver transplantation (LT) for metabolic liver disease in children in Pediatric Transplantation written by Eldredge et al 1 We would like to congratulate the authors for their excellent work to comprehensively review this field. In pediatric patients with inherited metabolic disorders (IMDs), metabolic decompensation can lead to severe neurological complications and even death despite appropriate medical and nutritional management.

…”

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confidence: 99%

The role of pediatric living donor liver transplantation for inherited metabolic disorders

Sakamoto,

Kasahara,

Mazariegos

2024

Pediatric Transplantation

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We read with great interest the recent article related to liver transplantation (LT) for metabolic liver disease in children in Pediatric Transplantation written by Eldredge et al. 1 We would like to congratulate the authors for their excellent work to comprehensively review this field. In pediatric patients with inherited metabolic disorders (IMDs), metabolic decompensation can lead to severe neurological complications and even death despite appropriate medical and nutritional management. LT has subsequently emerged as an increasingly important therapeutic approach for treating IMDs and offers the potential for a complete or partial cure of genetically acquired IMDs. As collective experience in

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Current status and future directions of liver transplantation for metabolic liver disease in children

Cited by 3 publications

References 128 publications

D-dimer Level Is Non-Specifically Elevated Post-Living-Related Liver Transplantation in Children

D-dimer Level Is Non-Specifically Elevated Post-Living-Related Liver Transplantation in Children

Deoxyguanosine kinase deficiency: natural history and liver transplant outcome

The role of pediatric living donor liver transplantation for inherited metabolic disorders

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