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Twitter debate: controversies in liver transplantation
  1. Oliver D Tavabie1,
  2. Ankur Srivastava2,
  3. Audrey Dillon3,
  4. Darius Mirza4,
  5. Steven Masson5,
  6. Philip J Smith6
  1. 1Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, UK
  2. 2Department of Gastroenterology and Hepatology, North Bristol NHS Trust, Westbury on Trym, UK
  3. 3Liver Unit, St James’ University Hospital, The Leeds Teaching Hospitals NHS Trust, Leeds, UK
  4. 4Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
  5. 5Liver Transplant Unit, Freeman Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
  6. 6Department of Gastroenterology, Royal Liverpool University Hospital, Liverpool, UK
  1. Correspondence to Dr Oliver D Tavabie, Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, UK; oliver.tavabie{at}nhs.net

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Key points

  • There is no ‘6-month abstinence’ rule for patients with alcohol-related liver disease in the UK.

  • Cannabis use is not an absolute contraindication for referral for transplant assessment.

  • Whether a new transplant centre should be a UK funding priority is currently debatable.

  • The advent of machine perfusion will increase the number of available grafts for transplantation.

  • Pregnancy is possible for patients post-transplant and should be discussed on a case-by-case basis.

Introduction

The first #FGDebates of 2021 tackled ‘Controversies in liver transplantation’ in a double-header inspired by the recent liver transplantation guidelines.1 2 The debates stimulated much discussion with nearly 900 tweets from over 100 participants across the two debates. This fantastic interaction generated a cumulative 3.7 million impressions worldwide with both debates ranking in the top 5 #FGDebates of all time for total impressions made. In this article, we aim to discuss the key discussion points from each of the #FGDebates.

Assessing patients with alcohol use disorders

Liver transplantation for patients with alcohol use disorders (AUDs) has historically been viewed as a controversial area for both the general public and healthcare profession. This was largely due to the perceived ‘self-inflicted’ component and the risk of recidivism post-transplant.3 However, the majority of our attendees felt that it was the correct time to assess our patient with an AUD (figure 1) and alcohol-related liver disease remains the most common aetiology at registration for liver transplantation in the UK with good long-term outcomes.4 A common misconception is that patients require a period of 6 months abstinence prior to referral for assessment. While a period of 3 months abstinence may demonstrate the potential for recompensation, there is no absolute rule for abstinence duration prior to assessment in the UK other than patients must be abstinent.1 However, these patients should be assessed for their individual risk of return to drinking and should engage with addiction services both preand post-transplantation.1 2

Figure 1

#FGDebate poll on transplant assessing a patient with alcohol-related liver disease.

It should be noted that steroid-refractory alcoholic hepatitis (AH) is not currently an indication for early liver transplantation in the UK. Despite the potential survival benefit previously demonstrated in steroid non-responders, a UK service evaluation of early liver transplantation for severe AH failed to transplant a single patient.5 There was a discussion as to why this occurred. In part, this may reflect a lack of validated criteria to select those individuals with severe AH who might benefit most from LT. In addition, there may be a lack of appetite among referrers and transplant clinicians in the UK. Currently, cases may be considered on an individual basis by the national appeal process1 or if liver insufficiency persists after 3 months of documented alcohol abstinence if their psychosocial risk is favourable. Further work is required to define the role of early liver transplantation for severe AH in the UK.

Assessing smokers and cannabis users

During the debate, we discussed both tobacco and cannabis use in transplant candidates (figure 2). Ongoing tobacco use continues to be a controversial topic in the context of liver transplant assessment despite evidence that active smoking post-transplant leads to reduced long-term survival.6 Current recommendations are that smoking is seen as a relative contraindication to transplantation and that all smokers should engage in a smoking cessation programme.1

Figure 2

Expert opinion from our discussion regarding whether cannabis or cigarette smoking should be seen as contraindications to transplantation.

The effect of cannabis use post-transplant is less clearly defined and whether it should affect a patient’s transplant candidacy was felt to be debatable. The discussion highlighted the paucity of data to suggest effect on post-transplant outcome. However, cannabis users are more likely to be smokers, have an AUD, use other illicit substances, suffer from mental health disorders and develop lung disease. While NHS Blood and Transplant do not state that cannabis use is an absolute contraindication to transplantation, it is stressed that a formal substance misuse assessment is required and adherence to agreed treatment and care plans is mandatory.7

Access to liver transplantation in the UK

The final key point from the first #FGDebate was patient access to liver transplantation in the UK. The centres delivering the UK liver transplant programme have been determined by where enthusiastic individuals interested in transplantation were based as opposed to clinical and geographical need. This has resulted in sections of the country not having a readily accessible transplant centre, most notably the north- and southwest of England, Wales and Northern Ireland (figure 3). While satellite centres and transplant networks have been established to try and address this,8 there are ongoing concerns that there is an inequity in access to liver transplantation causing increased patient morbidity and mortality.9 The potential location of an additional transplant centre is a ‘hot topic’ with modelling suggesting a centre in Bristol may have the greatest impact.9

Figure 3

A map of UK liver transplant centres.

However, there was significant debate as to whether the development of a new UK liver transplant centre should be a funding priority. While the field continues to expand, liver transplantation is required by a minority of patients with chronic liver disease (CLD). Furthermore, an additional liver transplant centre would require significant investment to establish and maintain. It would also be challenging staffing a new transplant centre given the shortage in staff numbers across the multidisciplinary team providing transplant care. Filling this void would require significant time and investment to ensure that a new centre would have an adequately trained and experienced transplant team. Given the rising prevalence of CLD in the UK, investing and focusing on screening and interventions to prevent the complications of CLD would be more effective in addressing rising mortality than a new transplant centre. The jury remains out on if and where a new transplant centre is needed.

Organ selection

The effect of the COVID-19 pandemic on organ donation and transplantation has highlighted the need to maximise our organ donor pool.10 As living donation is relatively uncommon in adult liver transplantation in the UK, most grafts are from deceased donors.2 Grafts are classified by mode of death of the deceased donor as either donation after brain stem death (DBD) organs or donation after circulatory death (DCD) organs. This classification is important as DCD grafts historically have been associated with a greater incidence of significant complications leading to increased patient mortality and morbidity. For these reasons, DBD grafts have been predominately utilised in the UK liver transplant programme.2 However, the rapidly developing field of machine perfusion techniques is likely to change the landscape of graft selection by increasing the utilisation of previously viewed marginal or high-risk grafts and narrowing the gap between DCD and DBD grafts.5 This should lead to increased transplantation rates with a knock-on effect of improved waiting-list survival.

Given the increased need for organ donors, we discussed other means of increasing the donor pool. Donors with either active or prior exposure to hepatitis B and C were previously excluded from organ donation. However, with improved management strategies for both viruses post liver transplant, there has been increased international utilisation of these organs in patients with and without prior viral exposure.11 12 While utilisation of grafts with exposure to both hepatitis B and C will increase the donor pool, the potential overall impact on the UK transplant waiting-list was felt to be modest due to the low prevalence of both viruses among donors.13

Abnormal liver function tests post-transplant

Abnormal liver function tests in the post-transplant patient can be a challenge to interpret and frequently are a cause for concern for the non-transplant physician. Alongside typical non-transplant causes, there are a number of specific causes which need to be considered. A practical algorithm is provided within the transplant guidelines which considers time post-transplant and likelihood of potential pathologies.2 When assessing the patient, we would recommend appropriate imaging to assess the graft, graft’s vasculature and biliary tree, a non-invasive liver screen including viruses such as cytomegalovirus and hepatitis E, and that a detailed immunosuppression history is taken with appropriate trough levels of immunosuppression agents. Early contact with the appropriate transplant centre is vital to collaboratively coordinate appropriate care to investigate and manage each patient.

Pregnancy post-transplant

Pregnancy post-transplant was once considered unfeasible and during the second #FGDebate, the discussion highlighted the ongoing concerns about this cohort. Liver transplantation reverses infertility associated with end-stage liver disease in the majority of women.14 Therefore, counselling patients about fertility and sexual health is an essential component of post-transplant care. It is recommended that patients wait for 1–2 years post-transplant prior to planning a family and that they should have satisfactory graft function for at least 3–6 months prior to conception.14 Patients should be managed in a multidisciplinary team with medical obstetric support. While no immunosuppression is completely safe in pregnancy, mycophenolate mofetil is contraindicated due to the risk of abortion, stillbirth and developmental abnormalities. There are no specific contraindications to vaginal delivery but caesarean section is more common in this population. Fetal outcomes continue to improve as our experience evolves with recent figures suggesting an 84% live birth rate in post-transplant women.15 This demonstrates that carefully planned pregnancies are possible post-transplant and should be discussed with patients on an individual basis.

Conclusion

As the subspecialty of liver transplantation continues to evolve, we need to continue to review how we select patients and deliver care to improve long-term outcomes. We are grateful for all of you who joined us for this #FGDebate and would encourage all of you to participate in our ongoing programme.

Ethics statements

Acknowledgments

We are grateful to all of the participants of both #FGDebates.

References

Footnotes

  • Twitter @DrPhilipJSmith

  • Contributors ODT drafted the initial manuscript. AS, AD, DM, SM and PJS critically appraised and revised the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Map disclaimer The depiction of boundaries on the map(s) in this article does not imply the expression of any opinion whatsoever on the part of BMJ (or any member of its group) concerning the legal status of any country, territory, jurisdiction or area or of its authorities. The map(s) are provided without any warranty of any kind, either express or implied.

  • Competing interests OT is a Trainee Associate Editor at Frontline Gastroenterology and has received grants for educational content from Gilead and for consumables from NIHR BRC. PJS is an Associate Editor at Frontline Gastroenterology. There are no other competing interests to declare.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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