Therapeutic potential of living donor liver transplantation from heterozygous carrier donors in children with propionic acidemia

Abstract

Background Current world experience regarding living donor liver transplantation (LDLT) in the treatment of propionic acidemia (PA) is limited, especially in terms of using obligate heterozygous carriers as donors. This study aimed to evaluate the clinical outcomes of LDLT in children with PA. Methods From November 2017 to January 2020, 7 of the 192 children who underwent LDLT at our institution had been diagnosed with PA (median age, 2.1 years; range, 1.1–5.8 years). The primary indication for transplantation was frequent metabolic decompensations in 6 patients and preventative treatment in 1 patient. Of the seven parental living donors, six were genetically proven obligate heterozygous carriers. Results During a median follow-up of 23.9 months (range, 13.9–40.2 months), all patients were alive with 100% allograft survival, and no severe transplant-related complications occurred. In the case of liberalized protein intake, they did not suffer metabolic decompensation or disease-related complications and made progress in neurodevelopmental delay and body growth, as well as blood and urinary metabolite levels. In one patient with pre-existing mild dilated cardiomyopathy, her echocardiogram results completely normalized 13.8 months post-transplant. All living donors recovered well after surgery, with no metabolic decompensations or procedure-related complications. Western blotting revealed that the hepatic expressions of PCCA and PCCB in one of the heterozygous donors were comparable to those of the normal healthy control at the protein level. Conclusions LDLT using partial liver grafts from asymptomatic obligate heterozygous carrier donors is a viable therapeutic option for selected PA patients, with no negative impact on donors’ and recipients' clinical courses.

Domino hepatocyte transplantation using explanted human livers with metabolic defects attenuates D-GalN/LPS-induced acute liver failure

“…A growing number of patients with monogenic metabolic liver diseases (such as urea cycle disorders, maple syrup urine disease, MMA, and PA) undergo LT worldwide [17][18][19][20][21]. The explanted livers from those liver transplant recipients with noncirrhotic liver-based metabolic disorders are morphologically, structurally, and functionally normal except for definite metabolic deficiency.…”

Liver transplantation for Homozygous Familial hypercholesterolemia: A retrospective analyses from Chinese experience

“…The information garnered from this article can serve as an important source of clinical evidence and procedures involving LT for the treatment of HoFH. Our center is particularly suited for conducting this review as nearly 1500 LTs, including over 800 pediatric LTs and almost 700 living donor LTs, have been performed at our center [4,5]. Our study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the local ethics committee.…”

Prevalence of propionic acidemia in China

“…This study also demonstrated that hepatic expressions of PCCA and PCCB was consistent at the protein level in both heterozygous donor and the healthy donor for the first time. Liver supply from relatives carrying heterozygous genes is relatively easy to obtain and less burdensome for patients’ families [ 85 ] (Additional file 1 ). For children with mild PA, prophylaxis is recommended for patients under one year of age [ 86 ].…”

“…It is undeniable that patients with PA may still develop complications even after LT, such as renal failure, hepatic artery thrombosis [ 86 , 87 ]. However, LT can largely prevent metabolic decompensation, achieve protein diet liberalization, improve neurodevelopmental delay to some extent, and may even treat cardiomyopathy [ 85 ].…”