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 have been 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).

Delphi 1:

The survey background questions indicated that the majority of respondents ( 72% of RD and 67% of MD respondents) had no direct experience with MSUD liver transplantation, but had experience in the use of liver transplantation in 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.

Delphi 1:

The survey background questions indicated that the majority of respondents ( 72% of RD and 67% of MD respondents) had no direct experience with MSUD liver transplantation, but had experience in the use of liver transplantation in other IEM.

Comments: 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.

Delphi 2:

There was consensus (82.5% of all respondents agreed) that individuals with MSUD should be in metabolic control prior to liver transplantation.

Comments: although this is optimal, those needing this form of treatment are those having the most problem of control

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 included continuous glucose infusion 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.

Delphi 1:

The survey background questions indicated that the majority of respondents ( 72% of RD and 67% of MD respondents) had no direct experience with MSUD liver transplantation, but had experience in the use of liver transplantation in other IEM.

Delphi 2:

There was consensus (91% of RD  and 83% of MD respondents agreed) that, for individuals with MSUD undergoing liver transplantation, catabolism should be minimized.

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) have indicated positive outcomes after transplantation 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.

Delphi 1:

There was no consensus (63% of RD and 50% of MD respondents agreed)  that and ad lib diet was appropriate post-transplant,

Comments: 5 of these respondents said that they had no experience with MSUD patients post-transplant.

There was no consensus (63% of RD and 50% of MD respondents agreed) that one could expect plasma BCAA and BCKA in the normal range after transplant.

Comments: the BCAA and BCKA may be somewhat higher than “normal”, but that would be of no clinical consequence.

Delphi 2:

There was consensus ( 82% of RD and 100% of MD respondents agreed) that  a regular diet is possible after transplantation.

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.

Delphi 1:

There was consensus (91% of RD and 83% of MD 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.

There was no consensus (73% of RD and 33% of MD agreed) that plasma amino acids should be monitored whenever liver function tests were performed.

Comments: 18% of RDs and 50% of MDs had no opinion on this statement.

There was consensus (100% of RD and 83% of MD agreed) that patients should be monitored for growth and nutritional status post-transplant.

Comments:apply the usual protocol with liver transplantation for other inborn errors of metabolism.

Delphi 2:

There was consensus (100% of all respondents agreed) that (dietary) transition counseling is necessary

There was consensus (100% of all respondents agreed) that post transplant monitoring for growth and nutritional status is necessary.

Nominal Group Session:

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.