Understanding "Marginal" Liver Grafts

Jiménez Romero C, Moreno González E, Colina Ruíz F, Carazo FP, Loinaz Segurola C, Rodríguez González F, González Pinto I, García García I, Rodríguez Romano D, and Moreno Sanz C. Use of octogenarian livers safely expands the donor pool. Transplantation 1999; 68: 572. The rapid growth of liver transplantation activity has been curtailed by the lack of organ donors and has led to an expansion in the number of patients on the waiting list. This growing imbalance between donor organ availability and the potential number of recipients is an international problem, and there is a pressing need to expand the donor pool. Various initiatives have been tried including: the introduction of the opt-out legislation (presumed donor consent), the incorporation of the Spanish system of donor coordination, the expansion of intensive care unit capacity, elective ventilation, and the development of split liver and living donation. Until relatively recently, transplant centers could be conservative with regard to liver donor selection. However, the shortage of liver grafts has led to the relaxing of selection criteria for donors to ensure that as many potential recipients as possible are offered transplantation. Many donor organs, which were previously not considered suitable for transplantation ("marginal" grafts), are now used. The term "marginal" was originally applied to grafts from "older" donors, however, that definition has changed and now it is used to refer to grafts from a "higher risk" group of donors based on demographic, clinical, laboratory, and histological data (Table 1).Table 1: Parameters for marginal donors Donor age above 50 years was considered to be a significant risk factor for liver transplantation outcome, however, over the last 10 years, this age limit has gradually risen and has now all but disappeared with the report from Jiménez Romero et al. (1) successfully utilizing donors more than 80 years of age. While it is clear that organs from younger donors are preferable, the liver does not become diseased as part of the normal aging process (2). With increasing donor age, livers tend to become smaller, darker (due to lipofuscin deposition), and develop a fibrous thickening of the capsule. There is no evidence to suggest that significant fatty infiltration is more common. Atherosclerosis, which commonly affects the vascular tree, may affect the celiac and hepatic arteries but is seldom a contraindication to liver transplantation (3). There is some evidence to suggest that older livers have a greater sensitivity to cold injury and thus a greater likelihood of impaired early graft function and prolonged cholestasis (2). Short ischemic times have been recommended to minimize preservation injury, and this would seem to be a sensible precaution (4). Allocation of these grafts needs to be carefully considered, and if possible, marginal grafts should be transplanted into clinically stable good risk recipients. Livers from younger donors should be preferred for high-risk recipients, such as those with complex surgical problems, or used for reduced or split liver grafts. At the other extreme of age, the lower limit for liver donation is not clear. Grafts from neonatal donors have been used (5), however, with livers from donors less than 3 months of age there is an unacceptably high incidence of hepatic artery thrombosis, which should exclude their use in all but exceptional cases. Other factors besides age are more important in the assessment of potential grafts and in particular the presence of hepatic steatosis. Donor age, obesity, and a history of high alcohol intake have all been associated with fatty infiltration. Severe macrovesicular fat infiltration (involving more than 60% of hepatocytes) is associated with an increased incidence of primary nonfunction (6), and these livers should not be used. Donor livers with mild to moderate macrovesicular fat infiltration (up to 45%) or with severe microvesicular steatosis have been associated with early graft dysfunction, but not usually primary nonfunction, and can be used (6, 7). The selection of the appropriate recipients for these livers has not been widely debated. We would favor their use in clinically stable recipients who will tolerate some early graft dysfunction until the complete functional and histological recovery of the graft. Other parameters of donor selection such as abnormal liver function tests, prolonged hospital stay (more than 3-5 days), cardiac or respiratory arrest with prolonged resuscitation or hypotension (>70 mmHg for more than 30 min), the use of inotropes in a vasoconstrictive dose, and severe systemic sepsis have all been associated with an increased risk of graft dysfunction (8). The use of marginal livers has increased the risk of primary graft dysfunction and may result in lower survival rates in some transplant centers (9, 10). However, there is a balance that needs to be achieved between access to grafts, deaths on the waiting list, and survival after transplantation. In the past, marginal grafts were used in seriously ill patients with poor graft and patient survival (11). However, this attitude is changing, and these grafts are being allocated to more stable recipients with satisfactory results. Retransplantation remains an important aspect underpinning the use of marginal grafts. Any movement toward the restriction of retransplantation for progressive poor early graft function will inevitably lead to a tightening of the criteria for acceptance of donor livers and a reduction in the number of grafts used. Currently, there would seem to be no upper age limit for liver donation, however, each donor must be evaluated with regard to other potential risk factors. Donor selection and organ allocation remain highly subjective, and in the absence of reliable laboratory tests (12), the decision whether to use a marginal graft is left to the judgment of the transplant surgeon. The definition of what constitutes a marginal graft will continue to vary between centers until reliable parameters are available for prospectively predicting early graft function. Hector Vilca Melendez Nigel D. Heaton Liver Transplant Surgical Service; King's College Hospital; London, United Kingdom