The positive impact of the COVID 19 pandemic on organ utilisation in liver transplantation

Abstract

Background

As the world recovers from the aftermath of devastating waves of an outbreak, the ongoing Coronavirus disease 2019 pandemic has presented a unique perspective to the transplantation community of ‘’organ utilisation’’ in liver transplantation, a poorly defined term and ongoing hurdle in this field. To this end, we report the key metrics of transplantation activity from a high-volume liver transplantation centre in the United Kingdom over the past two years.

Methods

Between March 2019 and February 2021, details of donor liver offers received by our centre from National Health Service Blood & Transplant, and of transplantation were reviewed. Differences in the activity before and after the outbreak of the pandemic, including short term post-transplant survival, have been reported.

Results

The pandemic year at our centre witnessed a higher utilisation of Donation after Cardiac Death livers (80.4% vs. 58.3%, p = 0.016) with preserved United Kingdom donor liver indices and median donor age (2.12 vs. 2.02, p = 0.638; 55 vs. 57 years, p = 0.541) when compared to the pre-pandemic year. The 1- year patient survival rates for recipients in both the periods were comparable. The pandemic year, that was associated with increased utilisation of Donation after Cardiac Death livers, had an ischaemic cholangiopathy rate of 6%.

Conclusions

The pressures imposed by the pandemic led to increased utilisation of specific donor livers to meet patient needs and minimise the risk of death on the waiting list, with apparently preserved early post-transplant survival. Optimum organ utilisation is a balancing act between risk and benefit for the potential recipient, and technologies like machine perfusion may allow surgeons to increase utilisation without compromising patient outcomes.

Introduction

The ongoing COVID- 19 pandemic has taken a toll on the conduct of medical practice across the world. Various countries suspended routine clinical practice indefinitely and converted their hospitals into solely COVID- 19 care facilities, whereas hospitals elsewhere took on guarded elective work in anticipation of an overwhelming wave of pandemic [1,2]. As was the case with all health care service delivery, organ donation and transplantation has been significantly impacted on by this unforeseen event.

Temporary restrictions were placed upon transplant centres in the United Kingdom, in response to the pandemic. As a result, transplant units saw varying degrees of impact on donation activity. In addition, the utilisation of organs also varied, with some centres becoming more cautious whilst other units increasing utilisation of marginal grafts for patient benefit. The pandemic seems to have presented a unique perspective of organ utilisation, a term that is poorly defined in recent transplant literature and recognised to be one of the current hurdles in transplantation [3,4]. Here we report how pandemic pressures impacted on organ procurement, utilisation, and transplantation in a high- volume liver transplant centre and assess their impact on early post-transplant survival.

Methods

Between March 2019 and February 2021, all donor liver offers received by our centre from The Hub, the IT infrastructure of National Health Service Blood & Transplant (NHSBT), the nodal agency overseeing transplant activity in United Kingdom, were reviewed. The World Health Organization declared COVID a ‘’pandemic of international concern’’ on March 11th, 2020 and therefore, we used this month to divide the duration of interest into two periods [5].

Offers from March 2019- February 2020 (Pre- Covid year) were reviewed separately from the offers received during March 2020- February 2021 (Covid year). Daily record of organ offers received by our centre from the Hub and pertinent transplantation activity were retrieved from core donor data forms, organ safety checklist and recipient data forms. Relevant donor data on the number of potential donor offers received per month and year, type of donor offer such as Donation after Cardiac or Brain death, number of accepted or declined donors, reasons for decline, demographic features of accepted donors and UK Donor Liver Index (UK DLI), and recipient details such as age of recipients, Model for End Stage Liver Disease (MELD) Score, waiting time on the transplant list were identified. Other peri transplant data such as timing of transplant was also noted. UK DLI is a measure of donor liver quality, the donor liver index, was developed and validated for the UK population of transplant recipients [6]. We defined acceptance rate as the percentage of donor offers that were accepted by us at initial offer irrespective of final allocation, and utilisation rate as the percentage of retrieved livers that were finally transplanted by our centre. In addition, early post-transplant survival of recipients have been reported.

Deceased donor liver allocation policies

Since early 2018, the NHSBT has employed the National Liver Offering Scheme (NLOS) based on the Transplant Benefit Score (TBS) for DBD adult liver allocation, in order to maximise post- transplant benefit in recipients [7]. The TBS is derived from a computer- based algorithm which incorporates seven donor characteristics and 21 recipient characteristics to obtain the highest TBS and identify the best donor- recipient match before offering organs to potential recipients in any of the seven liver transplant centres in the United Kingdom. Potential organs were considered a formal offer when offered by the Hub specifically to one of our waitlisted patients, based on decreasing level of priority, from super-urgent to elective. (‘Super urgent’ list includes very sick patients who will not survive for long without a liver transplant and includes patients with Hepatoblastoma and those waiting for a multi organ transplant).

If there were no patients on the super urgent list, or there was no match, the available liver is then offered to patients on the Liver Transplant List with the highest TBS. When declined, the organ may be offered again to the same or other centres up to seven times, depending on the next outcome of the matching algorithm. The offering of DCD livers is currently outside of the afore mentioned liver- allocation process. In the case of DCDs, offers are based on the location of the donor hospital. Any liver that is not accepted in this sequence is offered for one last time to all centres in the country simultaneously through the ‘fast- track’ offering system, in a final attempt to place the organ.

Statistical analysis

Data were analysed using Statplus v7. A significance level of 0.05 was used for all analyses; reported P are 2-tailed. Continuous variables are described as median and compared by the Kruskall- Wallis test or Mood's Median test, depending on their distribution. Categorical variables are reported as percentages (frequencies) and continuous variables as median (range). Association of categorical variables was assessed using χ2 test or Fischer's exact test, where appropriate. Survival statistics were represented using the Kaplan-Meier method and compared using Log rank tests.

Results

Overall organ acceptance and utilisation rates

From March 2019 to February 2021, our centre received a total of 3011 donor liver offers from 2627 potential deceased donors. 1668 (55.3% of 3011 offers) offers were from DBD donors and 1343 offers (44.6% of 3011 offers) were from controlled DCD donors. Overall, 875 donor offers were accepted at the time of initial offer, an offer acceptance rate of 29%. Of the accepted DBD offers (n = 585), 16.7% (n = 98) were allocated to a different centre based on priority. 83.2% (n = 487) of accepted DBD livers were retrieved for transplantation and 367 were successfully transplanted, an organ utilisation rate of DBD livers in the reported period of 75.3%. Of the accepted DCD offers (n = 290), 47.5% (n = 138) donors did not proceed to donation following treatment withdrawal and 13.4% (n = 39) livers were allocated to a different centre. 113 (39.1%) DCD livers were retrieved and 75 were transplanted, a DCD organ utilisation rate of 66.3% (Fig. 1 ). Quarterly acceptance and utilisation trend of livers at our centre during the period are in Table 1 .

Fig. 1.

Organ offers and utilisation during the entire study period (March 2019- February 2021).

Table 1.

Quarterly distribution of offer acceptance and utilisation rates.

	March-May	June-August	September-November	December- February
March 2019-February 2020
Acceptance rate	34.6% (125)	34% (144)	22.5% (120)	30% (130)
Utilisation rate	77.2% (68)	72% (54)	70.9% (66)	69.6% (55)
March 2020-February 2021
Acceptance rate	31.3% (59)*	34.2% (122)	24.6% (107)	29.1% (67)*
Utilisation rate	68% (34)*	77.3% (65)	68.9% (60)	86.9% (40)*

^⁎Quarters coinciding with the first and second waves of the pandemic.

Potential offers dropped by 56.5% (188 vs 433 offers) in the first COVID wave (early 2020) and 46.8% (230 vs 433 offers) in the second wave (late 2020). Although transplantation services recovered in between the surges, number of potential offers remained consistently 15.8- 18.2% lower in the quarters than 2019 levels (Fig. 2 ). Overall, organ offers reduced by 33% in the COVID year compared to 2019, and the rates of DBD and DCD transplantation reduced by 17.4% and 21.4%, respectively. Organ acceptance was highest (34.2%) in the second quarter of the pandemic year. Utilisation of retrieved livers was highest during the second wave (86.9%). The utilisation rates of DBD livers were consistent through all the quarters of the years, while DCD liver utilisation steadily rose through the COVID year (p = 0.016) (Fig. 3 ) (Table 2 ). There was no significant difference in weekend acceptance and utilisation rates of offers (p = 0.831, 0.561) in the two years. 42.5% (n = 188) transplants were performed in the night (8pm to 8 am).

Fig. 2.

Quarterly distribution of organ offers between March 2019 and February 2021.

*Quarters coinciding with the first and second waves of the pandemic.

Fig. 3.

Quarterly trend of utilisation of DBD and DCD livers between March 2019 and February 2021.

Table 2.

Organ offers and characteristics of utilization in the two years.

	Mar 2019-Feb 2020	Mar 2020-Feb 2021	p- value
Overall offers received	1803	1208	0.000
n(%)	929 (51.3)	739 (61.1)
DBD	874 (48.4)	469 (38.8)
DCD
DBD offers
n(%)	324 (34.8)	261 (35.3)	0.851
Accepted	263(81.1)	224 (85.9)	0.786
Retrieved	201(76.1)	166 (73.4)	0.448
Transplanted
DCD offers
n(%)	195(22.3)	95(36.3)	0.382
Accepted	94(48.2)	58(61)	0.039
Proceeded	42(58.3)	33(80.4)	0.016
Transplanted
UK DLI
n
DBD	1.16	1.14	0.527
Accepted	1.16	1.14	0.527
Transplanted	1.15	1.13	0.898
Non-transplanted	2.15
DCD	2.01	2.03	0.078
Accepted	2.22	2.12	0.638
Transplanted		1.85	0.068
Non-transplanted
Age (transplanted livers)
n (range)	51 (3- 84)	46 (3- 79)	0.021
DBD	55 (11–79)	57 (13–69)	0.541
DCD
DBD
% (n)	34.8%(324)	35.3% (261)	0.851
Acceptance rate	76.1%(201)	73.4% (166)	0.448
Utilisation rate
DCD
%(n)	22.3% (195)	20.4% (95)	0.382
Acceptance rate	58.3% (42)	80.4% (33)	0.016
Utilisation rate
Fast track
n (%)	95(31.5%)	64(29.3%)	0.590
Acceptance rate	34(72.3%)	23(79.3%)	0.495
Utilisation rate
Night- time transplant	98 (40.3%)	90 (45.2%)	0.300
(8 pm-8 am)	260 (27.6)	179(25.9)	0.831
n(%)	122 (73.7)	95(74.4)	0.561
Weekend activity
n(%)
Acceptance
Utilisation
Normothermic machine perfusion before transplantation	10 (4.1)	4 (2)	0.208
n(%)

Between March 2019 and February 2020 (Pre- COVID)

The year preceding the pandemic saw a total of 1803 liver offers, including 929 DBD (51.5%) and 874 DCD (48.4%) offers. Unsuitable donor history (40%, n = 540) was the most common cause of decline of organs at offer, followed by abnormal liver function tests (22%, n = 276) and unfavourable organ description (10%, n = 126). 105 (8%) offers were declined due to logistics like ongoing transplantations or clashing times, out of which 23 livers (21.9%) were accepted and transplanted by other centres. The median age of accepted donors was 56 years. The median age of transplanted livers were 52 years (51 years for DBD, 55 years for DCD). The median UK DLI of the accepted, transplanted, and non- transplanted DCD livers at our centre were 2.15, 2.01 and 2.22, and the same for DBD livers were 1.16, 1.16 and 1.15, respectively (Table 2). The overall rate of acceptance and utilisation in the year preceding COVID was 28.7% and 72.5%, respectively. The rate of acceptance and utilisation for DBD liver offers were 34.8%(n = 324) and 76.1% (n = 201), respectively. Similarly, the same for DCD were 22.3% (n = 195) and 58.3% (n = 42), respectively (Fig. 4 ).

Fig. 4.

Organ offers during the pre- pandemic year (March 2019- February 2020).

Between March 2020- February 2021 (COVID)

In response to increasing national viral burden from the COVID pandemic, the donors were thoroughly screened for COVID and nursed in COVID- free areas until donation. During the period, a total of 1208 deceased donor liver offers were received from 1034 potential donors, and only 38.8% of offers were from DCD donors when compared to 48.4% the preceding year (p = 0.000) (Fig. 5 ). Unfavourable donor history (32%) was the most common cause of decline. 63 (7%) livers were declined due to logistics, out of which 20 livers (31.7%) were utilised by other centres. 6% of declines were related to COVID (2% decline due to risk of COVID infection, 4% decline due to temporary activity suspension during the second wave). More number of accepted DCDs proceeded to donation in this year, compared to the previous year (p = 0.039). The median age of accepted donors was 51 years. The median age for transplanted livers was 48 years (46 years for DBD, 57 years for DCD). The median UK DLI of the accepted, transplanted, and non- transplanted DBD liver offers were 1.14, 1.14 and 1.13, and the same for DCD livers were 2.03, 2.12 and 1.85, respectively (Table 2). The overall acceptance and utilisation rates during the COVID year was 29.3% and 75%, respectively. The rate of acceptance and utilisation for DBD were 35.3% (n = 261) and 73.4% (n = 166), respectively. The same for DCD were 20.4% (n = 95) and 80.4% (n = 33), respectively (Fig. 5).

Fig. 5.

Organ offers during the pre- pandemic year (March 2020- February 2021).

Recipient waitlist time and short-term survival

In the pre- covid year, 210 transplants were performed on 206 adult recipients, including 19 super- urgent transplantations. 33 paediatric transplantations were performed for 7 super- urgent, 11 priority and 15 elective recipients. In the pandemic year, 161 adult liver transplantations were performed on 159 recipients, including 16 super- urgent liver transplantations. 147 patients were first- time, liver only recipients. 38 paediatric transplants were performed on 37 children, for 6 super- urgent, 6 priority and 26 elective indications.

There was no significant difference in the MELD scores, transplant waiting times of patients, or waitlist mortality rates for the two years (Table 3 ). However, the waiting time of patients transplanted with DCD in the COVID year was significantly longer than that of patients transplanted with DCD in the precovid year (123 days vs 84.5 days, p = 0.032). The same for DBD transplants in the two years were 36 days and 60 days (p = 0.06). For the pre covid year, the adult graft and patient survival at 1- year were 96.6% and 98.5%, and for paediatric population was 90.9% each. In the pandemic year, the adult graft and patient survival at 1- year were 97.5% and 98.7%, and for paediatric population was 89.4% and 91.8%, respectively (adults, p = 0.508; children, p = 0.616). While no instances of ischaemia- type biliary lesions were identified in the pre- covid era, 6% (n = 2) incidence of the same was noted in the DCD liver transplants performed in the covid year.

Table 3.

Recipient details.

	Mar 2019-Feb 2020	Mar 2020-Feb 2021	p- value
Recipient age
n(range)	53 (17–74)	55 (17–73)	0.106
Adult	5 (0–16)	4 (0–16)	0.712
Paed
UKELD n(range)	54(43–70)	54(43–68)	0.851
MELD n(range)	14(4–40)	12 (2–40)	0.543
Waiting time (adult)
n(range)	65 (1–1610)	63 (1–1825)	0.912
Routine	3(1–7)	2 (1–12)	0.129
Urgent
Waiting time (paed) n(range)
Routine	60 (1–459)	75 (3–1035)	0.385
Urgent	4 (2–11)	4 (2–14)	0.705
Priority	50 (70–120)	41 (4–142)	0.384
Waitlist mortality
n (%)	9 (6.4)	14 (8.9)	0.424
Survival (adult) 1 y
n(%)	202(96.6)	157(97.5)	0.508
Graft	203(98.5)	157(98.7)	0.655
Patient
Survival (paed) 1 y
n(%)	30(90.9)	34(89.4)	0.616
Graft	30(90.9)	34(91.8)	0.565
Patient

Discussion

Our report suggests that during the COVID year, we observed a 33% reduction in potential liver offers than the preceding year and performed 18.1% fewer liver transplantation. Adult transplant services reduced by 25%, but paediatric transplantations increased by 29%. In addition to reduced offers, 6% of offer declines occurred due to COVID related factors, further increasing the loss of offers. At the height of the first wave in Mar- May 2020, following the declaration of the global pandemic on 11th March 2020, overall organ transplantation rates in the United Kingdom were down to below 80%, yet maintaining services for the most urgent patients [8]. Other centres in North America found a 17% decline in organ recovery rates between two similar 90-day time frames in 2020 and 2019 and, consequently, a 18% decrease in the number of transplanted organs [9].

Policy changes during the pandemic

Waitlisted liver patients were prioritized by creating an adult high clinical urgency category to include patients with UKELD more than 60, selected HCCs, and selected CLD patients with a UKELD of less 60. All offers were targeted to these high urgency patients before being offered to non- urgent patients. Although NHS BT offered named DBD organs to centres based on matching (Nation Liver Offering Scheme), the receiving centre had the autonomy to use the organ to transplant another clinically urgent recipient, with appropriate explanation. This discretion was restricted to the first wave and did not extend to the second surge of the pandemic. For a brief period during the second surge, our transplantation services for adults were suspended owing to a severe shortage of critical care beds in the Trust. Soon after, transplantation restarted for paediatric patients and clinically urgent adult patients, this time with adherence to NLOS matching. During both surges, many nursing staff, including transplant coordinators, and consultant surgeons and registrars were redeployed to ICUs and other COVID- 19 related projects within the trust. Throughout the first wave, NHSBT also altered the deceased donor criteria primarily by restricting the donor age, an easily altered and yet unambiguous unit of measure for clinical decision- making in donor referral. Between 23rd March and 7th April 2020, DBD and DCD donor ages for potential donation referrals were restricted to <60 and < 50 years, respectively. DBD age restriction was eased to <75 years from 7th April and DCD restriction to < 60 years from 1st June 2020, as the pandemic lessened. On 29th June 2020, DBD and DCD age restriction were eased to < 80 and < 75 years respectively. Soon after, on 6th July 2020, the age restrictions would go back to pre- covid criteria [10]. The limitation was intended to maintain ICU capacity to accommodate COVID patients, while reducing donation activity just enough to preserve clinically urgent cardiac, liver, and paediatric transplantation. It also increased the probability of referred donors progressing to actual donation, making the diversion of healthcare capital during a pandemic more justifiable.

Reasons for decline and non-transplantation

Aside from the obvious and more common causes of organ decline (donor history and organ function), notably, on- going transplantation and clashing operating times consistently contributed to 7–8% of offer declines in both years, and one fourth of these rejected livers were transplanted by other centres (n = 43, 25.5%), denying access to transplantation to one in every seven patients on our waitlist in the two- year study period. No organs were directly declined due to lack of ICU beds in either year. However, 4% offer declines occurred due to programme suspension by the Trust during the second surge. There were no statistical differences in weekend transplant rates or night- time transplants in the two years. Notably, 40–45% of transplants continue to start in the odd hours of the night.

Changes in utilisation

DCD donor offers decreased in the COVID year (38.8% vs. 48.4%, p = 0.003), likely due to a more restrictive age criteria on donation during periods of the pandemic when compared to DBD donors. A greater number of accepted DCD offers proceeded to retrieval in the COVID year compared to the previous year (61% vs. 48.3%, p = 0.039), potentially owing to referral of only those donors that were more likely to proceed to actual donation. The DCD utilisation rates sequentially increased throughout the COVID year when compared to the preceding year (80.4% vs. 58.3 %, p = 0.016), while the DBD utilisation rates remained mostly unchanged (73.4% vs. 76.1%, p = 0.448). While the number of overall organ donors fell, the overall ‘quality’ of potential liver donors remained unchanged. Nevertheless, our study suggests a conventional approach to DBD utilisation, in comparison to a robust utilisation of DCD livers by transplant surgeons during the pandemic, with nearly similar early survival and acceptable ischaemic cholangiopathy rates of 6 % when compared to contemporary literature [11,12]. While direct causality testing for the observed changes are challenging as the reasons for this disparity are likely multifactorial, our national data published by the NHSBT from the first wave of the pandemic showed an increase in the retrieval rates from DCD donors, whereas their transplant rates remained unchanged (p = 0.2) [13]. Noticeably, the response of different liver transplant units in the United Kingdom have been diverse, owing to varied local impact of the virus and changes in the risk appetite of clinicians arising from the uncertainty posed by the pandemic. Reddy et al. reported at the start of the pandemic that 10 out of 17 major liver transplant centres across the world reduced their transplant activity in response to the COVID- 19 outbreak by employing a “sickest-first” approach [14]. The burden of the COVID-19 pandemic was clearly overwhelming on the healthcare system of most Western countries that saw severely declining rates of organ donation and transplantation when compared to the far East [15], [16], [17], [18]. From that perspective, the interim vigorous DCD utilisation strategy adopted at our centre appears to have been an attempt to bridge the gap between reduced donor offers in comparison to waitlisted patients. This need is reflected in the increased waiting time of patients transplanted with DCD livers in the covid year, when compared to the previous year. The vastly different allocation process of DCD and DBD livers in the United Kingdom may have, in some part, allowed for this fortuitous adaptation in an hour of need.

In conclusion, the pandemic has opened new avenues for discussion in healthcare, including the sphere of organ transplantation, and emphasises the need for more national and international efforts with public health specialists in the future that will sufficiently anticipate and allow planning for optimum healthcare delivery as the world enters the new era of pandemics. More specifically, our study was primarily aimed to explore the larger collateral impact of the pandemic on the donation- utilisation aspect of the transplantation process, and furthermore gauge its influence on early patient outcomes. The study has additionally unearthed certain existing pitfalls of the current pathway from referral to actual donation in the United Kingdom, the recognition of which may allow increased flexibility of the retrieval process in the future so that recipient centres can maximise utilisation while maintaining healthcare resource. Increasing the available transplant theatre capacity and staff in existing units is likely to prevent loss due to logistics, while establishing more transplant units in the United Kingdom could potentially distribute some of these waitlisted patients who would otherwise lose out on an opportunity for successful transplantation. In addition, novel technologies like machine perfusion can be utilised for its potential benefit in increasing organ utilisation, not only as a tool for assessing liver function but also to preserve the liver while resolving logistics. Studies have already suggested that machine perfusion can offer real benefits when compared to conventional cold preservation for kidneys and livers [19], [20], [21]. Nonetheless, it is important to remember that while maximising organ utilisation is aimed at meeting the needs of the waitlisted patients, it must not be at the expense of patient outcomes.

Author contribution statement

Aarathi Vijayashanker- study design; research; data gathering and statistical interpretation; writing; editing; and rewriting.

Varuna Aluvihare- writing; editing; and rewriting.

Abid Suddle- writing; editing; and rewriting.

Alberto Sanchez-Fueyo- writing; editing; and rewriting.

Miriam Cortes Cerisuelo- writing; editing; and rewriting.

Hector V Melendez- writing; editing; and rewriting.

Wayel Jassem- writing; editing; and rewriting.

Krishna V Menon- writing; editing; and rewriting.

Nigel Heaton- writing; editing; and rewriting.

Andreas Prachalias- writing; editing; and rewriting.

Parthi Srinivasan- study design; research; writing; editing; and rewriting; and guidance

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

A Perspective from a High-Volume Liver Transplant Unit in the United Kingdom