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

Abstract

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.

Guidelines for the diagnosis and management of methylmalonic acidaemia and propionic acidaemia: First revision

“…In transplanted MMA and PA patients diet normalisation, 42,84,89,90,93,94,103,104,112‐115 liberalisation or increased protein intake 75,76,78,80,83,88,91,96‐98,100,102,116‐118 or continuation of dietary restrictions 85,87,119 were all applied following transplantation. Liberalised and continuous diet both led to metabolically stable situations without acute decompensation 89,103 .…”

“…110 Organ transplantation of patients in acute metabolic decompensation should be avoided, as the procedure itself has the potential to cause further decompensation. 111 In transplanted MMA and PA patients diet normalisation, 42,84,89,90,93,94,103,104,[112][113][114][115] liberalisation or increased protein intake 75,76,78,80,83,88,91,[96][97][98]100,102,[116][117][118] or continuation of dietary restrictions 85,87,119 were all applied following transplantation. Liberalised and continuous diet both led to metabolically stable situations without acute decompensation.…”

Post-transplantation Outcomes in Patients with PA or MMA: A Review of the Literature

“…A retrospective analysis of 12 patients with PA reported no further episodes of acute metabolic decompensation following liver transplantation even with a less restricted dietary protein intake [10]. Similarly, Shanmugam et al [24] reported that of five children with PA and a median of eight episodes of decompensation per year prior to transplantation, no episodes of metabolic decompensation occurred either intraoperatively or immediately after transplantation when receiving a protein-unrestricted diet. In contrast, Kasahara et al [13] reported that following liver transplantation in Japanese patients with PA/MMA, recurrent metabolic decompensation was observed in 100% of patients despite the administration of protein restriction with medications (cobalamin, carnitine supplementation, and antibiotics to eradicate gut flora).…”

“…Infection is reported as a major cause of post-transplant deaths in patients with PA: Kasahara et al [13] reported that liver transplantation in nine patients with PA resulted in four sepsis-related deaths, equating to a mortality rate of 44%. However, some studies suggest that transplantation appears to be less of a risk in some patients with PA. For example, a recent retrospective analysis of liver transplantation by Shanmugam et al [24] reported survival in patients with PA to be 100% at a median follow-up of 32 months. It appears that survival following transplantation in patients with PA seems to be improving with greater experience of the procedure.…”

The concept of “domino” in liver and hepatocyte transplantation

“…Other important considerations include compatible blood groups, size-matched liver grafts, pathological examination of liver grafts, and post-transplant rejection monitoring. 44 , 46 …”