A Novel Strategy for Preventing Posttransplant Large-For-Size Syndrome in Adult Liver Transplant Recipients: A Pilot Study

There are two causes of graft compression in the large-for-size syndrome (LFSS). One is a shortage of intra-abdominal space for the liver graft, and the other is the size discrepancy between the anteroposterior dimensions of the liver graft and the lower right hemithorax of the recipient. The former could be treated using delayed fascial closure or mesh closure, but the latter may only be treated by reduction of the right liver graft to increase space. Given that split liver transplantation has strict requirements regarding donor and recipient selections, reduced-size liver transplantation, in most cases, may be the only solution. However, surgical strategies for the reduction of the right liver graft for adult liver transplantations are relatively unfamiliar. Herein, we introduce a novel strategy of HuaXi-ex vivo right posterior sectionectomy while preserving the right hepatic vein in the graft to prevent LFSS and propose its initial indications.

Polar Interactions at the Dimer–Dimer Interface of Methionine Adenosyltransferase MAT I Control Tetramerization

Catalytic MATα1 subunits associate into kinetically distinct homo-dimers (MAT III) and homo-tetramers (MAT I) that synthesize S-adenosylmethionine in the adult liver. Pathological reductions in S-adenosylmethionine levels correlate with MAT III accumulation; thus, it is important to know the determinants of dimer–dimer associations. Here, polar interactions (<3.5 Å) at the rat MAT I dimer–dimer interface were disrupted by site-directed mutagenesis. Heterologous expression rendered decreased soluble mutant MATα1 levels that appeared mostly as dimers. Substitutions at the B1–B2 or B3–C1 β-strand loops, or changes in charge on helix α2 located behind, induced either MAT III or MAT I accumulation. Notably, double mutants combining neutral changes on helix α2 with substitutions at either β-strand loop further increased MAT III content. Mutations had negligible impact on secondary or tertiary protein structure, but induced changes of 5–10 °C in thermal stability. All mutants preserved tripolyphosphatase activity, although AdoMet synthesis was only detected in single mutants. Kinetic parameters were altered in all purified proteins, their AdoMet synthesis Vmax and methionine affinities correlating with the association state induced by the corresponding mutations. In conclusion, polar interactions control MATα1 tetramerization and kinetics, diverse effects being induced by changes on opposite β-sheet loops putatively leading to subtle variations in central domain β-sheet orientation.