Introduction: Propionic acidemia (PA) and methylmalonic acidemia (MMA) are rare metabolic disorders characterized by enzyme dysfunction. Liver transplantation (LT) and combined liver-kidney transplantation (LT/KTx) are therapeutic options that provide massive enzyme replacement, stabilizing metabolically vulnerable patients and preventing the occurrence of disease complications. The objective of this study is to analyze the surgical outcomes of LT and LT/KTx in patients with MMA and PA.
Methods: This retrospective, monocentric, descriptive study includes all patients who underwent LT or LT/KTx between 2010 and 2023 for MMA and PA at our center. The association between morbidity, mortality, and variables of interest was evaluated using the Mann-Whitney test for quantitative variables and Fisher's exact test for qualitative variables.
Results: A total of 31 patients were included, with 23 diagnosed with MMA (median age 7.3 years(5.1-13.1)) and 8 with PA (median age 7.5 (6.1-13.6)). Twenty patients received LT, and eleven received LT/KTx, exclusively for MMA. After a median follow-up of 4.7 years (IQR 1.6-6.5), the survival rate was 96% (22/23) for MMA and 63% (5/8) for PA, with a median time to death of 14 days. Among MMA patients, 56.5% (n=13) developed major postoperative complications (Clavien-Dindo ≥ III), while 87.5% of PA patients experienced such complications. Only a minority of these complications were surgical. No perioperative factor analyzed was significantly associated with morbidity or mortality, except for preoperative renal function (p=0.048) and Prothrombin Time (PT) on day 3 (p=0.007). The results from this cohort were compared with those of liver transplantation for other indications. The occurrence of major complications was more frequent in the organic acidemia group and significantly higher in the PA subgroup. In particular, the mortality rate in patients with PA was significantly higher than in patients with MMA, although the sample sizes were small and not directly comparable. Our impression is that cardiac involvement in PA patients may play a crucial role in the response to post-operative hemodynamic fluctuations.
Conclusion: LT and LT/KTx for organic acidemias show surgical outcomes comparable to those of other liver transplantation indications. However, these procedures are associated with significant short-term morbidity, which is very specific to the diseases, including poorly understood cardiocirculatory morbidity. The high rate of short-term complications underscores the need for extensive perioperative management for these rare and fragile patients.