Auxiliary Liver Transplantation—A Form of Gene Therapy in Selective Metabolic Disorders

Shanmugam, NP; Perumalla, Rajasekar; Rela, M

doi:10.1016/s0973-6883(11)60076-5

Cited by 5 publications

(6 citation statements)

References 7 publications

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“…Intensive phototherapy from neonatal period is essential to avoid kernicterus but LT can be a therapeutic option for patients when phototherapy becomes ineffective or interferes with their life styles later . LT or auxiliary LTs have been performed as preventive procedures to counteract severe CNS‐related complications . In physiological condition, most of the bilirubin is bound to plasma albumin and excessive albumin‐unbound bilirubin is the source of kernicterus.…”

Section: Iem Currently Treated With Lt and Their Managementmentioning

confidence: 99%

Liver transplantation for pediatric inherited metabolic disorders: Considerations for indications, complications, and perioperative management

Oishi

Arnon

Wasserstein

et al. 2016

Pediatric Transplantation

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Liver transplantation is an effective therapeutic option for a variety of inborn errors of metabolism. This approach can significantly improve the quality of life of patients who suffer from severe disease manifestations and/or life-threatening metabolic decompensations despite medical/dietary management. Due to the significant risks for systemic complications from surgical stressors, careful perioperative management is vital. Even after liver transplantation, some disorders require long-term dietary restriction, medical management, and monitoring of metabolites. Successful liver transplant for these complex disorders can be achieved with disease and patient-specific strategies using a multidisciplinary approach. In this article, we review indications, complications, perioperative management and long-term follow up recommendations for inborn errors of metabolism that are treatable with liver transplantation.

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Section: Iem Currently Treated With Lt and Their Managementmentioning

confidence: 99%

Liver transplantation for pediatric inherited metabolic disorders: Considerations for indications, complications, and perioperative management

Oishi

Arnon

Wasserstein

et al. 2016

Pediatric Transplantation

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“…The underlying MLD were propionic acidemia (PA) in five, citrullinemia type 1 (CIT1) in three and Crigler-Najjar syndrome type 1 (CN1) in five patients. Details of three patients have been reported previously (Shanmugam et al 2011;Govil et al 2015).…”

Section: Resultsmentioning

confidence: 99%

“…Patient 11 with CN1 received a domino auxiliary graft from patient 5 with propionic acidemia (Govil et al 2015). All patients underwent intraoperative portal flow modulation as previously described (Reddy et al 2017;Shanmugam et al 2011;Rela et al 2015). None of the patients developed portal steal phenomenon in the immediate post-transplant period.…”

Section: Apolt Proceduresmentioning

confidence: 99%

Auxiliary Partial Orthotopic Liver Transplantation for Monogenic Metabolic Liver Diseases: Single-Centre Experience

et al. 2018

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Auxiliary partial orthotopic liver transplantation (APOLT) in metabolic liver disease (MLD) has the advantage of correcting the metabolic defect, preserving the native liver for gene therapy in the future with the possibility of withdrawal of immunosuppression. Methods: Retrospective analysis of safety and efficacy of APOLT in correcting the underlying defect and its impact on neurological status of children with MLD. Results: A total of 13 APOLT procedures were performed for MLD during the study period. The underlying aetiologies being propionic acidemia (PA)-5, citrullinemia type 1 (CIT1)-3 and Crigler-Najjar syndrome type 1 (CN1)-5 cases respectively. Children with PA and CIT1 had a median of 8 and 4 episodes of decompensation per year, respectively, before APOLT and had a mean social developmental quotient (DQ) of 49 (<3 standard deviations) as assessed by Vineland Social Maturity Scale prior to liver transplantation. No metabolic decompensation occurred in patients with PA and CIT1 intraoperatively or in the immediate post-transplant period on protein-unrestricted diet. Patients with CN1 were receiving an average 8-15 h of phototherapy per day before APOLT and had normal bilirubin levels without phototherapy on follow-up. We have 100% graft and patient survival at a median follow-up of 32 months. Progressive improvement in neurodevelopment was seen in children within 6 months of therapy with a median social DQ of 90. Conclusions: APOLT is a safe procedure, which provides good metabolic control and improves the neurodevelopment in children with selected MLD.

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“…APOLT was initially offered for children with NCMLD with the hope that future development of less invasive therapies like gene therapy or hepatocyte transplantation would provide permanent therapeutic options in their adult life. (1,(8)(9)(10) It was argued that once gene therapy is clinically available, the native remnant liver can be treated and that these patients will be able to come off immunosuppression. Although advancements have been made in this regard, it might take some time before clinical realization of these therapies happen, leading to a dampening enthusiasm in APOLT.…”

Section: Discussionmentioning

confidence: 99%

Auxiliary Partial Orthotopic Liver Transplantation for Selected Noncirrhotic Metabolic Liver Disease

et al. 2019

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Auxiliary partial orthotopic liver transplantation (APOLT) in selected noncirrhotic metabolic liver diseases (NCMLDs) is a viable alternative to orthotopic liver transplantation (OLT) as it supplements the function of the native liver with the missing functional protein. APOLT for NCMLD is not universally accepted due to concerns of increased technical complications and longterm graft atrophy. Review of a prospectively collected database of all pediatric patients (age ≤16 years) who underwent liver transplantation for NCMLD from August 2009 up to June 2017 was performed. Patients were divided into 2 groups: group 1 underwent APOLT and group 2 underwent OLT. In total, 18 OLTs and 12 APOLTs were performed for NCMLDs during the study period. There was no significant difference in the age and weight of the recipients in both groups. All APOLT patients needed intraoperative portal flow modulation. Intraoperative peak and end of surgery lactate were significantly higher in the OLT group, and cold ischemia time was longer in the APOLT group. There were no differences in postoperative liver function tests apart from higher peak international normalized ratio in the OLT group. The incidence of postoperative complications, duration of hospital stay, and 1‐ and 5‐year survivals were similar in both groups. In conclusion, we present the largest series of APOLT for NCMLD. APOLT is a safe and effective alternative to OLT and may even be better than OLT due to lesser physiological stress and the smoother postoperative period for selected patients with NCMLD.

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Auxiliary Liver Transplantation—A Form of Gene Therapy in Selective Metabolic Disorders

Cited by 5 publications

References 7 publications

Liver transplantation for pediatric inherited metabolic disorders: Considerations for indications, complications, and perioperative management

Liver transplantation for pediatric inherited metabolic disorders: Considerations for indications, complications, and perioperative management

Auxiliary Partial Orthotopic Liver Transplantation for Monogenic Metabolic Liver Diseases: Single-Centre Experience

Auxiliary Partial Orthotopic Liver Transplantation for Selected Noncirrhotic Metabolic Liver Disease

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