Model for end-stage liver disease (MELD) exception small-for-size syndrome

Authors


Small-for-size graft failure syndrome is a significant problem after living donor liver transplantation.1, 2 This syndrome may occur either because the graft/recipient ratio is less than predicted, resulting in a graft recipient-weight ratio of <0.8%3 or because of functional graft overflow as a result of either outflow obstruction or increased portal perfusion to the liver.4 Although preservation or reimplantation of tributaries of the middle hepatic vein may help decrease the incidence of small-for-size syndrome, when it occurs this condition significantly decreases survival.5

Pathogenic aspects of the small-for-size graft failure syndrome consist of portal hyperperfusion and insufficient venous outflow leading to arterial hypoperfusion with reduced liver function and reduced capacity for regeneration. Histologically, small-for-size graft failure syndrome is characterized by sinusoidal congestion and mitochondrial swelling with disruption of the sinusoidal lining, resulting in impaired bile secretion and severe cholestasis. Clinically, small-for-size graft failure syndrome is characterized by severe cholestasis, ascites, and coagulopathy.

Over time, many livers recover, but some do not. Early graft dysfunction predisposes recipients to sepsis. Lee and colleagues reported a significantly decreased survival rate in patients receiving grafts that had a graft weight/recipient ratio <1% (80% survival vs. 96%).5 Other authors have shown similar survival disadvantages in graft volume/recipient body weight ratio <0.8%, with some programs reporting survival rates <50% in this group.3, 6

Although there are very few objective criteria for determining when a liver becomes irreversibly damaged, recipients who have small-for-size grafts characterized by hyperbilirubinemia and increased international normalized ratio, and who are at <3 months posttransplantation appear to have a short window of time for safe retransplantation.2 However, because of the risk of sepsis and death, patients who meet the small-for-size criteria need to be urgently transplanted (within 6 weeks of initial transplantation) to avoid infection.

SYNTHESIS OF AVAILABLE DATA

There are sufficient data to justify additional priority for patients with small-for-size graft failure syndrome.

Proposal for Standardized Model for End-Stage Liver Disease Exceptions for Candidates With Small-for-Size Graft Failure Syndrome

We propose that candidates who develop small-for-size graft failure syndrome, defined as meeting 4 of the following 6 criteria, receive an initial model for end-stage liver disease score equivalent to a 50% mortality risk, and that the score should be increased by a 10% mortality equivalent every 3 months:

  • >5 days' after living donor liver transplantation;

  • Serum bilirubin concentration ≥10 mg/dL in the absence of rejection or common duct obstruction;

  • Bile duct ischemia (leak);

  • International normalized ratio ≥1.5;

  • Significant ascites as noted on clinical exam;

  • Biopsy with centrilobular ballooning, necrosis, and cholestasis.

These data elements should be prospectively collected by the Organ Procurement Transplantation Network/United Network for Organ Sharing for future revaluation of small-for-size as justification of additional model for end-stage liver disease priority.

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