Living donor liver transplantation for pediatric patients with metabolic disorders: The Japanese multicenter registry

Kasahara, Mureo; Sakamoto, Seisuke; Horikawa, Reiko; Umeshita, Koji; Mizuta, Koichi; Sato, Masato; Yagi, T.; Taguchi, Tomoaki; Inomata, Yukihiro; Üemoto, Shinji; Kuroda, Takeshi; Kato, Shingo

doi:10.1111/petr.12196

Cited by 77 publications

(63 citation statements)

References 27 publications

(39 reference statements)

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“…Previous reports, predominantly from Japan, suggested that it is safe to use living related donors and that the patients show sufficient metabolic correction in the medium term. (38) However, our view Original article | 429 is that the use of an unrelated LT donor is preferential in patients with PA.…”

Section: Discussionmentioning

confidence: 99%

Liver Transplantation in Children With Propionic Acidemia: Medium‐Term Outcomes

et al. 2020

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Liver transplantation (LT) for patients with propionic acidemia (PA) is an emerging therapeutic option. We present a retrospective review of patients with PA who underwent LT at a tertiary liver center between 1995 and 2015. A total of 14 children were identified (8 males) with median age at initial presentation of 3 days (range, 0‐77 days). Pretransplant median protein restriction was 1 g/kg/day (range, 0.63‐1.75 g/kg/day), 71% required supportive feeding, and 86% had developmental delay. Frequent metabolic decompensations (MDs) were the main indication for LT with a median age at transplantation of 2.4 years (range, 0.8‐7.1 years). Only 1 graft was from a living donor, and 13 were from deceased donors (4 auxiliary). The 2‐year patient survival was 86%, and overall study and graft survival was 79% and 69%, respectively. Three patients died after LT: at 43 days (biliary peritonitis), 225 days (acute‐on‐chronic rejection with multiorgan failure), and 13.5 years (posttransplant lymphoproliferative disease). Plasma glycine and propionylcarnitine remained elevated but reduced after transplant. Of 11 survivors, 5 had at least 1 episode of acute cellular rejection, 2 sustained a metabolic stroke (with full recovery), and 3 developed mild cardiomyopathy after LT. All have liberalized protein intake, and 9 had no further MDs: median episodes before transplant, 4 (range, 1‐30); and median episodes after transplant, 0 (range, 0‐5). All survivors made some developmental progress after LT, and none worsened at a median follow‐up of 5.8 years (range, 2‐23 years). LT in PA significantly reduces the frequency of MDs, can liberalize protein intake and improve quality of life, and should continue to be considered in selected cases.

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Section: Discussionmentioning

confidence: 99%

Liver Transplantation in Children With Propionic Acidemia: Medium‐Term Outcomes

et al. 2020

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“…In heterozygous females, liver OTC enzymatic activity ranges from complete deficiency to almost normal activity, even between females with the same mutations, because of the random inactivation of the X chromosomes. [8][9][10] In addition, intrahepatic OTC activity differs between different hepatic segments. 11 The measured enzyme activity usually correlates with the symptoms in females; however, there are several reports of females with normal enzyme activity and symptomatic hyperammonemia.…”

Section: Figen öZçay Et Al/experimental and Clinical Transplantation mentioning

confidence: 99%

“…In a recently reported Japanese study, 51 patients with UCDs underwent related living-donor liver transplant. 9 Their median age was 3.8 ± 4.6 years (range, 0.2-16 y). In that study, 19 of the 48 patients (39.6%) with OTC deficiency received maternal grafts, and no morbidities or mortalities were observed related to the use of heterozygous carriers.…”

Section: Figen öZçay Et Al/experimental and Clinical Transplantation mentioning

confidence: 99%

“…The 1-, 5-, 10-, and 15-year survival rates for patients and grafts were all 96.1%. 9 Histopathologic changes in livers of patients with UCDs have been evaluated in several studies. [12][13][14] Different findings from normal liver histology to nonspecific findings, such as inflammation, cholestasis, hepatocyte swelling, steatosis, fibrosis, cirrhosis, abnormal glycogen accumulation, and ultrastructural changes, have been reported.…”

Section: Figen öZçay Et Al/experimental and Clinical Transplantation mentioning

confidence: 99%

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Untitled

2015

Exp Clin Transplant

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Urea cycle defects are a group of metabolic disorders caused by enzymatic disruption of the urea cycle pathway, transforming nitrogen to urea for excretion from the body. Severe cases present in early infancy with life-threatening metabolic decompensation, and these episodes of hyperammonemia can be fatal or result in permanent neurologic damage. Despite the progress in pharmacologic treatment, long-term survival is poor especially for severe cases. Liver trans plant is an alternative treatment option, providing sufficient enzymatic activity and decreasing the risk of metabolic decompensation.Three patients with urea cycle defects received related living-donor liver transplants at our hospital. Patients presented with late-onset ornithine transcarbamylase deficiency, argininosuccinate lyase deficiency, and citrullinemia. Maximum pretransplant ammonia levels were between 232 and 400 μmol/L (normal range is 18-72 μmol/L), and maximum posttransplant values were 52 to 94 μmol/L. All patients stopped medical treatment and dietary protein restriction for urea cycle defects after transplant. The patient with late-onset ornithine transcarbamylase deficiency already had motor deficits related to recurrent hyperammonemia attacks pretransplant. A major improvement could not be achieved, and he is wheelchair dependent at the age of 6 years. The other 2 patients had normal motor and mental skills before transplant, which have continued 12 and 14 months after transplant. Hepatic artery thrombosis in the patient with the ornithine transcarbamylase deficiency, intraabdominal infection in the patient with argininosuccinate lyase deficiency, and posterior reversible encephalopathy syndrome in the patient with citrullinemia were early postoperative complications. Histopathologic changes in livers explanted from patients with ornithine transcarbamylase deficiency and citrullinemia were nonspecific. The argininosuccinate lyase-deficient patient had portoportal fibrosis and cirrhotic nodule formation.In conclusion, liver transplant was a lifesaving procedure for our patients. Proper timing for transplant is important because high ammonia levels may result in permanent neurologic damage; however, transplant at younger ages also may increase morbidity.

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“…(1) This observation may be useful for future consideration of these options in children, particularly for conditions such as primary hyperoxaluria and methylmalonic acidemia, where the slow, but inevitable, terminal renal decline has been conventionally used as a trigger for transplant. (5) In such circumstances, an earlier elective LT may be preferential and could potentially defer or avoid the renal operation. This could have important longterm benefits for children as longevity of renal grafts appears to be shorter than the liver ones.…”

mentioning

confidence: 99%

Metabolic Indications for Pediatric Liver Transplantation: A Slow Train Coming

Hadžić

2019

Liver Transpl

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Living donor liver transplantation for pediatric patients with metabolic disorders: The Japanese multicenter registry

Cited by 77 publications

References 27 publications

Liver Transplantation in Children With Propionic Acidemia: Medium‐Term Outcomes

Liver Transplantation in Children With Propionic Acidemia: Medium‐Term Outcomes

Untitled

Metabolic Indications for Pediatric Liver Transplantation: A Slow Train Coming

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