Reply.

Abstract

Potential conflict of interest: Nothing to report. TO THE EDITOR: We thank Rammohan et al. for the comment on our article. As the authors highlight, the reported rates of hepatic artery thrombosis (HAT) in propionic acidemia (PA) patients who undergo liver transplantation (LT) are higher than in other indications of LT.1 As described in the article, the rate of HAT in our series was 33% (2/6), which is similar to rates reported by other groups.1 The overall incidence of HAT in the last 10 years in our center for non‐PA indications was 3.5% (4/113): 3.7% (3/81) in whole liver graft transplantation and 3.1% (1/32) in living donor liver transplantation (LDLT). In the 2 HATs described in our series of transplanted PA patients, no anastomotic stenosis cases were observed in the interventional radiologist room. A third patient presented a vasospasm of the hepatic artery. Although technical issues cannot be completely ruled out, the higher incidence of HAT observed in all the reported series requires the assessment of other physiopathological explanations. Considering the alterations observed in our patients in the thromboelastography with normal coagulation parameters, it could be hypothesized that some propionate metabolites may interfere in the patient’s hemostasis. Although there is not any evidence in the literature supporting arterial wall compliance abnormalities in PA patients, we highlight in the text the subjective feeling of the surgical team that the consistency of the arterial wall was lower than normal. Moreover, in 2 patients, a vasospasm without thrombosis was detected during the surgical procedure. One of them was completely solved using intra‐arterial vasodilators, and the other one finally developed HAT 36 hours after the first procedure. Taking into account these observations, the use of continuous venovenous hemodiafiltration to remove procoagulant metabolites or more aggressive anticoagulant prophylaxis could be assessed in these patients. In our experience, when the inherent predisposition to HAT is joined with complex vascular reconstruction, as is usually seen in LDLT, the rate of thrombosis increases. Given the high rate of HAT observed, the use of the arterial conduit directly from the recipient aorta has been proposed as an alternative in our center. This approach has been adopted taking into account the experience in Alagille syndrome, another indication for LT related to higher rates of HAT.3 As stated by Rammohan et al., auxiliary partial orthotopic liver transplantation (APOLT) can be a good treatment option for selected noncirrhotic inborn errors of metabolism. This technique has potential benefits over the conventional orthotopic liver transplantation (OLT) as part of the native liver is left in place and can function as a back‐up if the donor graft fails. Moreover, by avoiding the anhepatic phase, the risk of metabolic decompensations during the surgery is diminished.4 Moreover, the possibility of performing gene therapy in the future is left open. Although the possibility to perform APOLT in this type of patients is currently being evaluated at our institution, other negative aspects must be taken into account. Mainly, PA patients seem to require a significantly higher amount of liver volume to avoid metabolic decompensation compared with patients with other inborn errors of metabolism. For this reason, APOLT receptors still have a risk of severe decompensations which could lead to a severe deterioration of their quality of life. In our series, no patient has presented decompensation either during the surgery or during follow‐up, presenting stabilization or improvement in the neurologic impairment in all patients 1 year after LT. It will be very important to know the metabolic evolution of PA patients receptors of APOLT in terms of toxic metabolites, neurological evolution, and number/severity of metabolic crises. Many aspects remain unresolved in the indication of the transplant and the perioperative management of PA patients. The low frequency of the disease and the heterogeneity in follow‐up make it difficult to generalize the results. Multicenter studies that involve a metabolic team, pediatric hepatologist, and LT surgeons are necessary to answer these questions.