The first liver transplants in patients with MSUD were undertaken because the patients had liver failure due to toxicity or infection unrelated to their MSUD (F.53, F.38, F.63, F.35). The normalization of BCAA and α-ketoacids in these first patients suggested that transplantation could be an alternative to dietary treatment in otherwise healthy patients with MSUD. Detailed clinical studies are reported for 27 patients, who had liver transplantation as a treatment for their MSUD (F.422, F.35, F.54, F.23).  In the gray literature there are summaries of experiences of 37 patients transplanted between 2004 and 2009 (G.43) and other commentaries that vary in their assessment of the risks versus the benefits of liver transplantation (G.50, G.31, G.49, G.23, G.21, G.48).

The Delphi survey and the Nominal Group Processes indicated that the majority of respondents had no direct experience with liver transplantation in individuals with MSUD, but had had experience with liver transplantation for other IEM.

The Clinic for Special Children and the University of Pittsburgh Medical Center have reported (F.35) successful outcomes using their guidelines for interventions before and during transplantation surgery on 11 patients, aged 1.9-20.5 years. These patients had plasma BCAA and urinary α-ketoacids in or near the treatment range (accomplished through dietary means) and had had no metabolic decompensation in the previous 3 weeks.

The Delphi survey and Nominal group process indicated that the majority of respondents had no direct experience with MSUD liver transplantation, but had experience in the use of liver transplantation in other IEM. Comments included that while control of BCAA prior to transplantation is optimal, in reality, those with poor control would probably benefit most from the curative effects of liver transplantation.

The Clinic for Special Children and the University of Pittsburgh Medical Center have reported (F.35) successful outcomes using their guidelines for interventions before and during transplantation surgery on 11 patients, aged 1.9-20.5 years. Their protocol includes continuous glucose infusion, which is necessary to prevent or minimize catabolism, monitoring of sodium/water homeostasis to avoid brain edema, and access to plasma amino acid analyses to monitor BCAA levels.

The Delphi survey and Nominal group processes indicated that the majority of respondents had no direct experience with MSUD liver transplantation. However they agreed that recommendations used when an individual with MSUD is undergoing any surgery would be appropriate in the perioperative period of the transplant patient.

Evidence from five reports (F.23, F.53, F.63, F.35, F.422) and 8 reviews, expert opinions and commentaries (F.89, G.31, G.23, G.50, G.48, G.49, G.21, G.43) indicates positive outcomes after surgery. For patients with MSUD who received a transplanted liver, normalization of plasma BCAA occurred within 6-12 hours of surgery; they also had normal or near-normal blood BCAA and urinary BCKA and some slight elevations of allo-ILE when on an ad lib and unrestricted protein diet post-transplant. They had no metabolic decompensation during intercurrent illnesses.

In the Delphi survey, 63% of RDs and 50% of MD agreed that an ad lib diet was appropriate post-transplant, with 5 of these respondents saying that they had no experience with MSUD patients post-transplant. There were the same percentages of agreement with the statement that one could expect plasma BCAA and BCKA in the normal range after transplant. One comment stated that they may be somewhat higher than “normal”, but that would be of no clinical consequence.

There were no published reports of dietary counseling for transitioning to a post-transplant diet, nor were there data given of either diet analysis or nutritional laboratory assessment after the transition.

• Transition counseling: 91% of RDs and 83% of MDs (Delphi 1) and 100% of all respondents (Delphi 2) agreed that post-transplant patients may need counseling to transition from a diet with medical food and very low-protein foods to a “regular diet” with the DRI for protein, energy and other nutrients.
• Laboratory monitoring: 73% of RDs and 33% of MDs agreed that plasma amino acids should be monitored whenever liver function tests were performed; 18% of RDs and 50% of MDs had no opinion on this question.
• Monitoring growth and nutritional status: 100% of RDs and 83% of MDs agreed that patients should be monitored post-transplant. Although respondents did not have much experience with this patient group, this was recognized as the usual protocol with liver transplantation for other inborn errors of metabolism.
• “Medicalizing” patients: There was some concern expressed at the Nominal Group Session that continued monitoring by the genetic team post-transplant may be a burden (financially and psychologically) on patients and their families.