Discussion

This study is the first to address the outcomes of second transplant centre opinions (STCOs) in candidates for LT. Over an 8-year period, STCOs remained a small proportion of LT assessment activity (1.3%), and questions are raised about future planning for such referrals and pathways. Our study highlights that over half (57%) of the incoming patients for STCO remain unsuitable for a full repeat LT assessment. When patients were not initially listed in our centre, only eight patients (2% of total not listed cohort) were referred for an STCO elsewhere. Of these, nearly 2/3 (62%) were not listed in another centre suggesting similar practice in LT centres. To extrapolate overall practice, pooling incoming and outgoing STCOs to/from our centre over the time period revealed only 19% were deemed suitable to list for LT in the second centre with the main reasons for initial unsuitability the risk of alcohol addiction/relapse and medical/anaesthetic (too high) risk. The question of resource utilisation thus to perform a full STCO second LT assessment may be raised.

In the UK, there are only seven adult LT Units serving the whole population. The comparatively small size of the country and intercentre geographical distance allows a unique situation whereby STCOs may be more feasible than in larger countries. Collaborative working between centres along with governing LT committees (The UK Liver Advisory Group – with pan-LT centre representation) allows, where possible, a degree of standardisation of care and assessment between units; however, there is not currently a uniform national LT assessment process. Collaborative inter-LT unit working was recently seen during the COVID-19 pandemic where a minority of waitlisted patients were transferred between the seven LT centres due to COVID-19 related capacity issues. UK LT centres also have a hub-and-spoke outreach model with referring centres facilitating incoming referrals but early repatriation following a transplant operation in rare cases. This allows care closer to home—a benefit for patients, especially when longer travels to LT centres involved. It has however been shown that despite the UK’s size and only seven LT centres, disparities exist within the UK for accessibly and equity of care for LT depending on proximity to a transplant centre.6 It remains an aim that all patients have equal and fair access to LT assessment—including STCOs—as close to home where possible. Monitoring of time delays (and outcomes) for STCOs, especially with the impact of COVID-19 pandemic, may be best served by an electronic national referral system or a unified national LT database tracking patient referral times, complemented by demographics, LT assessment details, waiting list events, LT details and the follow-up/outcomes and death. Such a database will allow transparency for patients and planning of resources moving forwards. This may serve as a platform for a linked-up STCO programme between centres. The volume of patients in the UK we hypothesise would not be large for STCOs as evidenced by our study; however, such a system may be more streamlined and by facilitating remote technologies, more equitable for patients and allow quicker decision making for STCOs. In our study, some adverse clinical events during the waiting time for the STCO occurred—a risk of decompensated cirrhosis. One patient within our cohort who developed advancement of hepatocellular carcinoma and one patient died prior to repeat LT assessment. This once again highlights the need for a streamlined STCO process and the importance of realistic communication with patients suffering from end-stage liver disease as to the fragility of their condition and a parallel palliative care referral if already declined by an index LT centre. Only 11% of patients had a palliative care referral documented in notes, leading to a change in our assessment process in 2016 introducing palliative care referrals as part of the listing meeting outcomes.

At present with increasing waiting times for patients in the COVID-19 pandemic era, along with perennial organ shortages, moves are also afoot to expand indications for LT. We hypothesise that the number of STCOs may escalate along with competition for grafts in the setting of finite resources. A robust and collaborative system for patients along with good communication for patients not listed will be imperative. Also, the indications for LT are indeed evolving. Currently, in the UK, a pilot scheme is underway for LT in acute on chronic liver failure (ACLF), and there remain global calls for LT to be explored in acute alcoholic hepatitis (AAH) with European and US centres already transplanting for this indication.7 8 LT for AAH remains contentious; thus, the role of STCOs may become more frequented if transplanting this indication becomes common practice in the UK. Patients with grave prognosis requiring consideration of LT for AAH or ACLF do not however have time to wait for STCOs by conventional outpatient referral pathways; thus, remote or virtual opinions/MDTs may be employed if asked for by patients. Our study showed that discussions of STCO cases in principle by the second centre often provided an outcome and may negate need for patient travel and also may be done in an expedient fashion. Having a standardised uniform inter-LT centre process for STCOs between units may be an area for exploration especially in the era of evolving LT indications and transplanting clinically sicker patients. The advent of telemedicine recently in the COVID-19 pandemic9 also may be used for such patients with remote MDTs now embedded features of UK clinical practice. This may speed up referral times and timely decision making.

Second opinions (SOs) are well established in several field of medicine such as oncology.4 For patients with a cancer, SOs can play an important role in the delivery of their care under multiple aspects, whether curative or palliative. In the oncological setting, Hillen et al4 have reported in a systematic review that patient-driven SOs rates ranged from 1% to 88%. These were related to higher education, higher familiarity with the medical system, more social support and being non-religious.4 Patients’ primary reasons were mainly a perceived need for acquiring more certainty or confirmation, a lack of trust and dissatisfaction with the first specialist and/or a need for more information. Reported rates of diagnostic or therapeutic discrepancies between the first and SOs have in other studies ranged from 2% to 51%.2 3 Already regional centres of excellence are established to discuss most cancers in the UK, giving matching or different opinions from local MDTs. Medical practice remains evidence based or based on guidelines; complex cases discussions can sometimes lead to professional-patient disagreement. In this setting, SOs can be effective in reassurance of both physician and patients,10 especially when different teams (in different centres) come to similar treatment conclusions. Understandably, LT units might have different views regarding patients’ risk factors, especially in the setting of medically/anaesthetically ‘too high risk’. In addition, patients’ perception and trust towards the assessing transplant physician or LT centre might differ. SOs can however be detrimental in certain circumstances as they may delay definitive decisions or patients’ treatment, be duplicative in nature and costly. This time delay is critical in the setting of decompensated cirrhosis in patients with reduced lifespan.11 The route of STCO may facilitate second centre expedient review, if STCO coming direct from the first centre LT team (34% of our incoming STCOs), rather than an incumbent delays asking a primary care physician or original referring physician to facilitate. A counterargument is that if patient declined first centre listing, having time to reflect and consider the outcome, along with discussion with referring physician who may have a long-established rapport with patient, is often in the patients’ best interests. Such as reinforcement of initial centre outcome by local teams may explain the small number of STCOs encountered. Of the incoming STCOs to our unit, 34% were requested by the declining LT centre (the rest/majority requested by patient to assessing local physician in the LT centre to action or by the discretion of the assessing physician).

In our study within the incoming STCOs, 15/23 (65.2%) were patient driven, of whom three were added on our waiting list. Of these patients added, the LT indication was ArLD, and the reason for turning down from the first transplant centre was high risk of alcohol relapse/recidivism in all three cases. The patients were entered into a formal alcohol liver transplant MDT clinic engaging in modification and amelioration of their alcohol risk behaviour through work with the MDT team as recommended in current UK guidelines.12 While there are ethical and financial considerations towards repeating LT assessments in all patients who have been declined LT at one unit due to alcohol risk, we have shown that significant improvements can occur in some patients with allowing them access towards LT.13 In the outgoing cohort, 3/8 STCOs (indications: ArLD, chronic liver graft rejection and NASH) were patient driven. Of these, only one was added on the waiting list and transplanted (indication: NASH). The other five patients were referred for a STCO by the transplant physicians directly from our unit to another LT centre and of these two were added on the waiting list. Whether STCOs should be mandatory for NHSBT could raise logistical and geographical issues. Also a mention of STCOs could be considered in the information that patients receive in the first centre assessment, without detracting the focus negatively from the initial MDT assessment. The most optimal strategy and pathway for this remains to be further evaluated.

Our study had a number of strengths, including tracking all seven LT centres in the UK. The relative small size of the UK and only seven centres with collegiate working lent to a robust view of activity incoming and outgoing from our centre and by default from other centres too. This could be complemented by a pan-UK national collaboration. To the best of our knowledge, the current study represented the first of its kind as outcomes of second opinions for LT have never been reported. The novel findings allows potentials for future planning of LT assessments between centres and also tracking of outcomes in a more patient-centric and transparent way. Some limitations exist, first the retrospective study design and potential selection bias. Although cross-checking with the national NHSBT UK data failed to identify additional STCOs patients who were transplant patients, we acknowledge that some of them still may have gone to second centre, been assessed but not listed. Having a national aligned data capture mechanism for STCOs would allow this to be monitored. However, there may have been some patients who received a STCO that we were unaware of. Moreover, our data may not be generalisable to other countries where different aetiologies for transplant dictate and different assessment processes. A major short-falling identified from this study was the documented recommendation for palliative care referral to local physician in 11% of cases. The listing meeting data collection MDT presentation since 2016 has included a specific outcome on MDT mentioning palliative care referral recommendation to local referring physician to improve on this figure in those patients not listed. Practically, when patient is contacted regarding not being listed, it is not common practice to discuss palliative care referral by telephone; a patient may be pre-emptively warned during the LT assessment regarding this, however, as part of a parallel strategy, or seen after LT assessment in a clinic. Patients are informed verbally of outcomes from our listing meeting and not formally by letter (a letter goes to referring physician). The modality of informing patients of transplant MDT discussions and outcomes is an avenue for exploration. In our centre, patients are informed by a coordinator/physician at the end of the assessment process with a formal letter to referring physician and general practitioner. Utilisation of patient and public involvement groups may aid with standardising the best format for communication outcomes in this setting between LT units. The utilisation of face-to-face clinic discussions of outcomes should not be underestimated where possible and if geography allows.