LAUSR

To the Editor With interest we read the article by Uchida et al. about the indication and outcome of liver transplantation (LT) in 13 patients with a mitochondrial disorder (MID) with liver involvement and acute liver failure in ten of these patients.1 MID was due to variants in MPV17 (n = 6), TRMU (n = 2), NDUFA9 (n = 1), and MTND1 (n = 1). Nine patients survived LT during a median followup of 4.7 years (range: 1.3– 5.8 years).1 The study is appealing but raises comments and concerns. A limitation of the study is that the genetic defect was identified in only 10 of 13 patients.1 Though biochemical investigations of the liver homogenate revealed complex I respectively complex III deficiency in the three patients without a genetic diagnosis, the diagnosis of a MID remains unconfirmed. The deficiency of complex I or complex III can be secondary to drugs, inflammation, or ischemia. We should be told why LT was carried out in three patients without genetic confirmation of a MID. A further limitation is that the degree of mtDNA depletion secondary due to MPV17 variants was not provided. Knowing the amount of mtDNA depletion in the 6 patients carrying MPV17 variants is crucial as it may strongly determine the phenotype and thus the outcome after LT.2 A further limitation of the study is that the medication the 13 patients needed to regularly take after LT was not provided. From a number of immunosuppressants, it is well known that they are mitochondriontoxic and may worsen the phenotype (e.g., tacrolimus).3 Particularly among the nonsurvivors, it should be discussed whether the necessary immunosuppressive medication contributed to the fatal outcome of these 4 patients. Patient 4 experienced visual loss at the age of 5 years, which is why Leber's hereditary optic neuropathy (LHON) was suspected. However, LHON usually starts in adolescence; therefore, LHON in this patient is rather unlikely. A further argument against LHON is that the patient did not carry any of the four primary LHON mutations. A third argument against LHON in this patient is that LHON hardly goes along with liver involvement. Was visual loss due to optic atrophy in this patient? Interestingly, patient 3 experienced an ischemic stroke prior to LT.1 We should be informed about the cause of stroke in a 6monthold child, particularly if there were risk factors such as arterial hypertension, diabetes, hyperlipidemia, or atrial fibrillation. Since no multimodal magnetic resonance imaging (MRI) had been carried out, it remains unclear whether the “stroke” was in fact a “strokelike lesion (SLL),” being a common cerebral manifestation of MIDs, particularly in mitochondrial encephalopathy, lactic acidosis, and strokelike episode (MELAS) syndrome.4 Nine patients were treated with a diet prior to LT. We should be told which type of diet was applied. Particularly, we should know whether any of these 9 patients received a ketogenic diet, which is known to prevent the generation of intrahepatic triglycerides.5 Seven of the 13 patients underwent a cerebral MRI prior to LT. We should be told about the indication to perform a cMRI. Was this in the context of the diagnostic workup or did these seven patients present with clinical manifestations of central nervous system involvement in addition to liver involvement? There is a discrepancy between the abstract and the main text. In the Abstract section, the median followup period was 1.8 years, whereas in the Results section median followup was 4.7 years.1 This inconsistency requires clarification. Overall, the study has several limitations, which challenge the results and their interpretation. The genetic cause of liver failure or liver cirrhosis should be known in MID patients scheduled for LT. In patients with liver failure due to mtDNA maintenance disorders or due to variants in mtDNAlocated genes, the amount of depletion respectively heteroplasmy rates should be provided. Since LT requires longterm immunosuppression, mitochondriontoxic immunosuppressants should be avoided.