Liver Transplantation for Propionic Acidemia: Evidence From a Systematic Review and Meta-analysis

Abstract

Background. The worldwide experience of liver transplantation (LT) in the treatment of propionic acidemia (PA) remains limited and fragmented. This review aims to provide a comprehensive and quantitative understanding of posttransplant clinical outcomes in PA patients. Methods. MEDLINE, Embase, and the Cochrane Library databases were searched for studies focusing on PA patients who underwent LT. The pooled estimate rates and 95% confidence intervals (CIs) were calculated using a random-effects model with Freeman-Tukey double arcsine transformation. Results. Twenty-one studies involving 70 individuals were included. The pooled estimate rates were 0.95 (95% CI, 0.80-1.00) for patient survival and 0.91 (95% CI, 0.72-1.00) for allograft survival. The pooled estimate rates were 0.20 (95% CI, 0.05-0.39) for rejection, 0.08 (95% CI, 0.00-0.21) for hepatic artery thrombosis, 0.14 (95% CI, 0.00-0.37) for cytomegalovirus/Epstein-Barr virus infection, and 0.03 (95% CI, 0.00-0.15) for biliary complications. The pooled estimate rates were 0.98 (95% CI, 0.88-1.00) for metabolic stability, 1.00 (95% CI, 0.79-1.00) for reversal of preexisting cardiomyopathy, and 0.97 (95% CI, 0.78-1.00) for improvement of neurodevelopmental delay. A large proportion of patients achieved liberalization of protein intake posttransplant (pooled estimate rate 0.66 [95% CI, 0.35-0.93]). Conclusions. Despite the risk of transplant-related complications, LT is a viable therapeutic option in PA patients with satisfactory survival rates and clinical outcomes. Given the diversity in neurological assessment methods and the inconsistency in the achievement of dietary protein liberalization across different studies, consensus on neurological evaluation methods and posttransplant protein intake is necessary. Longer-term clinical outcomes of LT for PA warrants further investigation.

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

“…Despite following a strict protein restriction and pharmacological intervention, PA patients still suffer frequent metabolic decompensations and subsequent devastating long-term complications [ 6 , 7 , 18 ]. As a kind of enzyme replacement therapy, LT has been performed in 67 PA patients with 75 liver grafts to date [ 10 , 11 , 13 – 15 , 19 – 34 ]. The overall patient and graft survivals were 80.6% and 72.0%, respectively (Table 3 ).…”

“…Hepatic artery thrombosis (HAT), one of the most life-threatening LT-related complications, is more frequent in pediatric LT, with an estimated rate of 4–8% [ 35 ]. However, the overall rate of HAT in historical PA cases was significantly high at 17.5% [ 11 ]. Therefore, it was once believed that patients with PA are more prone to develop HAT after LT [ 14 , 15 ].…”

“…Since replacing the enzyme-deficient liver with a metabolically normal liver could help regain partial PCC activity, after the first attempt in 1991, liver transplantation (LT) has emerged as a novel therapeutic option for selected PA patients who, despite strict dietary and medical intervention, still experience frequent metabolic decompensations or cardiomyopathy [ 11 – 15 ]. In some centers, early LT has been offered as a preventative treatment for metabolically stable pediatric PA patients without metabolic decompensation and severe neurological or cardiac sequelae [ 13 , 14 , 16 ].…”

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.…”

The re-occurrence of dilated cardiomyopathy in propionic acidemia after liver transplantation requiring heart transplant, first case from Middle East

“…Liver transplantation has been used for patient with frequent metabolic decompensations and was shown to be beneficial in propionic acidemiarelated dilated cardiomyopathy. 2 However, progression of cardiomyopathy, or, in rare cases, new-onset dilated cardiomyopathy in the immediate post liver transplant period are now considered well-known complications. Interestingly, Berry et al reported the first case of recurrent dilated cardiomyopathy 3 years after liver transplant.…”