In the past, the ideal donor was defined according to the following criteria: age below 40 years, trauma as the cause of death, donation after brain death, hemodynamic stability at the time of procurement, no steatosis or any other underlying chronic liver lesion, and no transmissible disease, who has no characteristics that may predispose his or her organs to graft failure after transplantation. Because of current organ shortage, all other deceased liver donors present a continuum of increased risk of graft failure compared with the ideal donor. The extended criteria donor (ECD) designation is meant to describe a deceased donor with substantially increased risk of graft failure compared with the ideal donor.
During the last decades, several studies have tried to define parameters and cut-off values for ECD in liver transplantation. Although there is still no universally accepted definition of ECD within the transplant community, the term generally refers to donor factors predisposing recipients to poor initial graft function and/or increased long-term risk, with the attendant risk of compromise of late graft function and recipient survival. These donor factors are numerous and include advanced donor age, female gender, hypernatremia, vasopressor requirement, prolonged hospitalization, extended duration of nonperfusion because of cardiac arrest, as well as prolonged cold ischemia time, hepatic steatosis, positive hepatitis B and C serology, and procurement after cardiac death.
There is significant heterogeneity in the use of extended criteria allografts across different countries and different centers, depending on the impact of organ shortage on waiting list mortality, local or regional policies, and the presence of alternatives to deceased donor transplantation. The central concerns are how to safely expand the donor pool with respect to specific quantification of risk, how to optimally allocate extended criteria allografts, and what information should be provided. Finally, the Paris consensus meeting with the contribution of experts from Europe, the United States, and Asia declared that donor quality represents a continuum of risk rather than ‘good or bad’, declaring that using an ECD is needed, even if it generates increased morbidity and mortality.
There is general consensus that the criteria fall into 2 categories of risk: (1) graft dysfunction and (2) disease transmission.

(1) Donor risk factors for graft dysfunction
1. Donor age
Changes associated with aging may decrease the regenerative capacity of the transplanted liver and make it more susceptible to ischemia/reperfusion injury, particularly with increasing cold ischemia time (CIT). The increased prevalence of steatosis in older livers can further delay graft function. Advanced age also increases the severity of hepatitis C virus (HCV) recurrence. The Paris consensus meeting reported that there is no absolute limit of donor age for liver transplantation (LT), however, it is strongly recommended not to allocate elderly donors to HCV-infected recipients.
2. Steatosis
Although steatosis can regress within weeks after LT, early functional recovery and regenerative capacity are significantly impaired with steatotic allografts, mostly because of more severe ischemia-reperfusion injury. Microvesicular steatosis apparently has less influence on ischemia-reperfusion injury and poor graft function than macrovesicular steatosis. Mild macrovesicular steatosis (<30%) has minimal impact on liver function post-transplantation, provided that CIT is short. When macrovesicular steatosis exceeds 60%, there is a consensus for discarding allografts because of a high rate of primary nonfunction (PNF). The use of grafts with moderate steatosis (30%-60%) remains a challenging issue. Recipient selection and minimal CIT are paramount to the successful utilization of moderately steatotic allografts as a period of delayed allograft function is expected.
3. Hypernatremia
Hypernatremic donors were previously considered as ECDs, because high serum sodium levels have been associated with decreased graft survival and function. It was thought that decreased graft survival and function were caused by cellular swelling, which occurs as a result of transition from an extracellular hypernatremic state to intracellular osmolality; there phenomenon lead to poor results. However, recent studies have revealed that hypernatremia is not correlated with graft survival and function. We can say that hypernatremia, less than 160 mEq/L is not an absolute contraindication to accept a liver graft per se, however, it is recommended to consider that an accumulation of risk factors might enhance their influence on the outcome.
4. Abnormal liver function test
There is no clear upper limit in serum transaminases that is a contraindication. The elevated liver function tests (LFT) are not specific, and do not give a key to the problem itself. Also a normal or near normal LFT is not a guarantee that there are no significant parenchymal lesion. During the Paris consensus meeting in 2008, it was also agreed that in the case of a marked increase in the γGT level, and/or an increased INR, the other donor factors, including a history of alcohol abuse and non-alcoholic steatohepatitis (NASH), should be carefully assessed before procurement is considered, and a liver biopsy is warranted.
5. Cold ischemia time
Prolonged CIT is an independent risk factor for the development of delayed graft function and PNF. UNOS/OPTN registry data has shown that, for every hour of CIT above 8 hours, the adjusted risk of graft failure increases by 2% (95% CI=1-3%). This has been confirmed in the continental European liver transplant experience; every 15-minute increase in CIT increases 1-year graft failure risk by 0.9% (95% CI=0.5-1.3%). Liver grafts from elderly donors and/or donor with steatosis are even more affected by prolonged CIT and preservation injury. In this group, optimal liver function can be best achieved when CITs are kept less than 8 hours. These results emphasize the need to shorten CIT as much as possible in the case of ECDs.
6. Donation after cardiac death
LT from non-heart-beating donors, now termed donation after cardiac death (DCD), is a promising way to increase the supply of organs. It currently accounts for 5% to 6% of liver transplants in the US and up to 20% in the UK. In controlled circumstances, the organs are retrieved after a standoff period of 2 to 5 minutes after death is certified. In some countries, only uncontrolled DCD, including patient death on admission and/or unsuccessful resuscitation, is accepted because of ethical consideration. In either controlled or uncontrolled DCD situations, the organs are subjected to a variable period of warm ischemia, which predisposed them to PNF, delayed graft function, or irreversible ischemic like diffuse cholangiopathy. It has been possible to achieve good results with an incidence of PNF below 15% and a lower incidence of biliary complications with specific measures. These measures include judicious donor selection, including donor age below 40 years and no steatosis, a specific resuscitation technique, including preservation of the organ with systemic heparin, the use of extracorporeal oxygenation, a short warm ischemia time (less than 15 minutes), and a short CIT (less than 10 hours). Although this procedure is limited to selected centers with specific protocols, DCD has the potential to increase the donor pool by 10% to 20%.
7. Split liver
Even if split-liver allografts are procured from young donors with normal parenchyma and short CIT, they should be considered extended criteria grafts for the following reasons:(1) the graft volume is generally lower than the recipient’s standard liver volume, and (2) there are higher technical requirements, and nonoptimal positioning of the partial graft may result in compromised venous outflow, which can cause more frequently poor early graft recovery compared with whole LT. Split-LT for 2 adults has been performed in select transplant centers with better results for right allografts versus left allografts. Adult transplantation with a left graft remains a challenging technical procedure with a high risk of PNF due to insufficient parenchymal volume. Split-LT can be considered only in optimal donors and yields at least 1 extended criteria allograft. The use of left allografts cannot be widely applied to adults but are best suited for pediatric recipients in whom split-LT offers excellent results.

(2) Donor risk factors for disease transmission
1. Donors with infection
Anti-HBC-positive donors
The major limitation to using liver grafts from anti-HBc-positive but HBsAg-negative donors is the potential risk of de novo HBV infection after transplantation. However, an overall low risk of HBV reactivation has been shown when treated with nucleoside analogs and hepatitis B immunoglobulin; therefore, anti-HBc-positive grafts are no longer rejected in many transplant centers.
Anti-HCV-positive donors
Initially, HCV Ab-positive donors were rejected due to the concerns of viral transmission and accelerated HCV recurrence. Preliminary reports have been published with short follow-ups and no differences in outcomes with the use of HCV Ab-positive grafts. Furthermore, it has been clearly shown that the survival and progression of HCV disease are similar to HCV Ab-negative allografts. Transplantation with HCV Ab-positive donors may lead to more advanced fibrosis, but this seems dependent on certain risk factors such as older age grafts. With the increasing availability of direct-acting antiviral agents, early treatment of HCV Ab-positive patients likely decreases the risk of fibrosis progression.
2. Donor with malignancy
The incidence of cancer in donors in approximately 3%, and the risk of transmitting malignancy by transplantation of an organ is roughly 0.01%. In 2003, a diverse group of transplant experts convened to review the current understanding of tumors in transplantation and to make specific recommendations about the organ utilization from donors with a history of malignancy. At this symposium, Glioblastoma multiforme, melanoma, choriocarcinoma, and lung cancer were determined to be absolute contraindications to organ donation. For common cancers such as breast and colon cancers, although advanced-stage disease was considered an absolute contraindication, early stage disease may be permissible for donation, depending on the exact tumor stage and the disease-free interval.

Donor risk index
Feng, et al. analyzed 20,000 transplant from the Scientific Registry of Transplant Recipients (SRTR) database and developed a donor risk index (DRI), which is calculated from seven donor and two transplant variables that were found to be independently associated with an increased risk of graft failure. These included donor > 40 years, donor height, donation after cardiac death, split/partial grafts, cerebrovascular accident or other cause of death, cold ischemia time, and organ sharing outside the local donor service area. Although a conclusive statement on the impact of graft steatosis could not be made due to incomplete data in the registry, the analysis of Feng, et al. highlights the relevant donor risk factors and supports a clear correlation between organ quality and post-transplantation outcome.

ECD grafts are thought to be of lower than average quality, associated with poor post-transplant outcomes or an increase in disease transmission. However, grafts have been traditionally thought of as suboptimal or even marginal, can be used safely through careful selection of both donor and recipient risks. Developing strategies for the continued expansion of the acceptable ECD pool are crucial to combating the shortage of organs.

References
1. Gordon Burroughs S, et al. Optimal utilization of extended hepatic grafts. Surg Today 2009;39:746-751
2. Feng S, et al. Expanded criteria donors. Clin Liver Dis 2014;18:633-649
3. Nemes B, et al. Extended criteria donors in liver transplantation part I: reviewing the impact of determining factors. Expert Rev Gastroenterol Hepatol 2016;10:827-839
4. Durand F, et al. Report of the Paris consensus meeting on expanded criteria donors in liver transplantation. Liver Transpl 2008;14:1694-1707
5. Routh D, et al. Changing pattern of donor selection criteria in deceased donor liver transplant: A review of literature. J Clin Exp Hepatol 2013;3:337-346
6. Feng S, et al. Characteristics associated with liver graft failure: The concept of a donor risk index. Am J Transplant 2006;6:783-790
7. Wiesner RH, et al. Report of the first international liver transplantation society expert panel consensus conference on liver transplantation and hepatitis C. liver Transpl 2003;9:S1-9
8. Feng S, et al. Tumors and transplantation: the 2003 third annual ASTS state-or-the-art winter symposium. Am J Transplant 2003;3:1481-1487
9.Vodkin I, et al. Extended criteria donors in liver transplantation. Clin Liver Dis 2017;21:289-301