Learning objectives.
By reading this article you should be able to:
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•
Explain the reasoning behind selection of an appropriate donor graft.
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•
Outline the selection process for potential graft donors.
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Describe the care provided to the living donor.
Key points.
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Differing societal attitudes about death account for the divergence in worldwide practice regarding organ donation after death and living donor transplantation.
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The outcomes of living donor liver transplants are at least equal to those for deceased donor transplants.
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The main priority during the transplantation process should be to mitigate all risks for the donor.
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The selection process for potential donors is necessarily complicated and time-consuming.
In the early stages of liver disease, the organ can undergo some degree of self-repair. However, as the disease progresses, ongoing chronic inflammation leads to scarring and fibrosis, which distorts the macroscopic and microscopic anatomy and leads to cirrhosis. The cause of the underlying liver disease is discoverable in ∼90% of patients, allowing treatment options in the early stages. As cirrhosis progresses to end-stage liver disease (ESLD), these interventions become less effective until eventually, the only remaining realistic treatment is replacement of the failing organ – liver transplantation (LT).
There are many causes of chronic liver disease (CLD), which may progress over time into ESLD. Over the last two decades, the number of deaths related to ESLD has steadily increased. More than two million deaths each year are attributed to CLD of which liver cancer (38%) and cirrhosis (62%) are the most common causes of mortality.1 Geographically, CLD resulting from chronic hepatitis B virus (HBV) infection is still seen predominantly as an Asian-Pacific problem; alcohol-associated liver disease is considered a major cause of cirrhosis across Europe and Latin America. The increase in the number of cases of non-alcoholic fatty liver disease is perceived as a developing problem worldwide. Whilst vaccination programmes and antiviral medications are used to prevent and treat HBV and hepatitis C virus (HCV) infections, the epidemics of alcohol-related and obesity-related liver disease are both harder to manage and control.
Background
Liver transplantation has been established as the treatment of choice in the management of ESLD. As a surgical procedure, it originated in the late 1960s using organs retrieved from deceased donors, but it was not until the late 1990s that the potential for living donor grafts was fully appreciated.2,3 As liver transplant surgery became increasingly accepted as a viable treatment option, a huge increase in the demand for transplantable donor organs followed.
For example, in the United States in 2019, the number of liver transplants increased by 40.8% over the previous decade to 8896 (adult and paediatric). Only 524 (5.9%) of these transplants were from living donors.4 At the end of 2019, the number of patients remaining on the waiting list was 12,767, with another 13,298 removed (mostly transplanted or deceased) and 13,093 added over the previous year. Two-thirds of patients on the waiting list remain on the list for >1 yr, and potential recipients are presenting at an older age and at later stages in their disease with higher model for end-stage liver disease (MELD) scores when compared with previous years.5
The need for suitable donor organs has not been met by the availability of deceased donor organs alone, but this shortfall has in some way been mitigated by increasing the use of organ grafts from living donors. An alternative approach to overcome donor organ shortage is to accept more marginal donor organs that would have previously been rejected for reasons of quality. These extended criteria donors are often older and less healthy with inferior hepatic function. Organ donation often occurs after the diagnosis of brain death, but donation after circulatory death is becoming increasingly common. The technological advancement in ex situ/ex vivo oxygenating machine perfusion devices able to preserve donor organ function or, indeed, improve organ quality by limiting the damage from ischaemia–reperfusion injury, also has the potential to increase the pool of donor organs.6
Across the world, societies have disparate cultural and religious views regarding death and organ donation, which has led to a divergence in attitudes towards organ donation after death. Together, these facts provide some insight into why the dominant practice in the West is donation after death (accounting for ∼90% of liver transplants), whereas living donation holds the corresponding position in the East (Fig 1).7
Fig. 1.
Worldwide data on liver transplantation activity (persons per million) in 2019, comparing living donor and deceased donor liver transplantation volumes by country.7 Reproduced with permission.
This review gives an overview of the process of living donor liver transplantation (LDLT), highlights the differences between LDLT and deceased donor liver transplantation (DDLT) and focuses on the importance of the care of the living donor.
The LT procedure
Liver donor grafts are procured in one of three ways:
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(i)
a whole liver graft from a deceased donor after brain or circulatory death;
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(ii)
a split liver graft from a deceased donor; or
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(iii)
a partial liver graft (using either the left or right liver lobe) from a living donor.
The choice of transplant technique is often directed by both the medical condition of the potential recipient and the availability of a suitable organ or graft. Both recipients and donors (deceased and living) go through a rigorous process to assess suitability. With organs being a scarce commodity, this process of selection and matching of the donor to recipient is extensive and time consuming, requiring input from the many transplant-associated specialties.
When a potential organ from a deceased donor is identified, a recipient is called into the hospital to undergo transplantation. Occasionally, for reasons of quality, the organ is rejected, and the transplantation procedure is cancelled, forcing the recipient to hope for another opportunity later. This cycle may then be repeated until the patient receives a transplant, is removed from the waiting list, or deceases while waiting for an organ.
During the work-up process, potential recipients are usually assessed for their suitability for a living donor transplant. They are encouraged to identify a potential donor from within their network of family and friends, but on rare occasions, an ‘altruistic donor’ may approach the centre to offer their services as a potential living donor.8 Compared with those undergoing DDLT, recipients in LDLT usually present with preserved liver function, lower MELD scores, and in better general health (Table 1). They also have the benefit of a scheduled surgery, which allows for opportunities to optimise a recipient's condition before surgery.
Table 1.
Comparison of the advantages and disadvantages for living donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT).
| Type of procedure | Advantages | Disadvantages |
|---|---|---|
| LDLT | Recipients often present earlier in their disease process Reduced time on waiting list Better donor graft quality:
Better recipient preparation:
|
Risks to donor:
Small donor graft size Requires two specialised teams at the same time Better outcomes linked with greater experience |
| DDLT | Whole organ donor graft Easier surgical technique |
Often reduced donor graft quality:
|
Surgical aspects of the transplantation procedure
In DDLT surgery, after hepatectomy of the native liver, the donor organ is either implanted with the donor inferior vena cava (IVC) remaining intact (classic approach), or with the donor hepatic veins attached to the recipient's preserved IVC (piggyback approach). The portal vein, hepatic artery and bile duct anastomoses procedures are mainly identical for both approaches.
For LDLT, only a part of a liver will be transplanted. Most centres performing adult LDLTs use the right lobe from the donor because it is an appropriate graft size for an adult. This right donor lobectomy is technically more difficult and, although every effort is made to preserve the anatomy of the portal structures, usually results in shorter bile duct and blood vessel lengths leading to more technically challenging anastomoses. The whole left lobe (or left lateral lobe) can also be used, but it is generally much smaller (∼30%) and usually only suitable for a child or small adult. The choice of donor graft is predicated by the size of the graft being adequate for the recipient and the size of the remnant being enough for the donor (Fig 2).
Fig. 2.
Surgical techniques for living donor liver transplantation showing: (a) right lobe and (b) left lobe donor grafting. Ao: aorta ; IVC: inferior vena cava.
Graft selection for size
It is of great importance to select the appropriate graft for LDLT. The screening for both the donor and the recipient aims to predict both the size of the donor graft and the donor remnant accurately. This is usually performed with CT imaging, using software programmes to volumetrically model the structure of the donor organ. The graft must be large enough both to provide adequate early liver function and to cope with the recipient's portal blood flow. Too high a portal flow may cause graft damage, impair subsequent liver regeneration and lead to early graft failure often equated with small-for-size-syndrome (SFSS). The medium-term graft survival is reported as being worse for recipients with SFSS, but with enhanced care, the longer-term survival appears to be at a similar level to recipients who did not receive too small a graft.9 Transplant centres usually aim for a donor remnant liver volume of >30% and a graft-to-recipient weight ratio (GRWR) of >0.8%. This provides enough margin of safety for the donor, who will rapidly regenerate new liver tissue over the next few weeks and months, whilst providing sufficient immediately functioning liver mass for the recipient's metabolic, synthetic, and detoxifying needs.
Graft anastomosis
In LDLT, the venous outflow often requires hepatic vein reconstruction using cadaveric donor veins for an end-to-side anastomosis onto the recipient's IVC. It is important to maximise the venous outflow from the graft to reduce congestion. The portal vein inflow and hepatic artery anastomoses are usually simpler end-to end anastomoses, although the short vessel lengths can cause problems requiring some modification before reperfusion. The biliary attachment may be a simple end-to-end anastomosis but is often completed as a Roux-en-Y hepaticojejunostomy.
Prolonged portal vein clamping can cause splanchnic organ congestion and oedema, which can be eased using a temporary portosystemic venous shunt draining blood directly from the portal vein to the IVC or renal vein. These shunts are usually removed before reperfusion, when optimal portal flow is needed.
Veno-venous bypass is another technique sometimes used to improve haemodynamic stability during the dissection and anhepatic phases, where blood is diverted around the portal system from a drainage catheter in a femoral vein, through an extracorporeal circulation system, and back to an axillary vein via another drainage catheter. The procedure does not come without risk and its use is often subject to the surgeon's or the centre's preference.
Graft inflow modulation in living donor grafts
After reperfusion and successful haemostasis, the blood flow through the graft must be assessed to ensure adequate arterial flow in the presence of high portal flow. This is especially important in smaller grafts relative to recipient size (GRWR ≤0.8). Graft inflow may need to be modulated to protect the graft; this can be achieved in many ways. Ligating the splenic artery, thereby increasing hepatic artery flow, which in turn decreases portal flow by means of the hepatic artery buffer response, is a popular first choice surgically.10 Many other portosystemic shunts are possible, the choice of which is patient-specific and based on the centre's experience. It can also be achieved by reducing the cardiac output and splanchnic vascular volume/flow using drugs such as vasopressin, octreotide, or esmolol.11
Anaesthesia for living donor recipients
The plan for anaesthesia for both LDLT and DDLT recipients is the same. The conventional view is that a balanced general anaesthesia technique using a volatile anaesthetic agent for maintenance should be used.12 Large-bore vascular access for the rapid transfusion of blood products is essential. Some invasive monitoring is standard (arterial and central venous catheters), although several other modalities are often used (transoesophageal echocardiography, bispectral index monitoring, arterial pressure waveform analysis, pulmonary artery catheter), depending on local practice.
The procedure is divided into the same three phases as for DDLT: the dissection and hepatectomy phase (where the liver is mobilised and the vessels and bile duct are divided), the anhepatic phase (where the recipient's liver is removed and replaced by the donor graft), and the post-reperfusion phase (where the donor graft is reperfused, haemostasis is achieved, and the biliary system is reconstructed). Each phase has its own set of anaesthesia-related problems.13
At the end of surgery, tracheal extubation is often performed and the patient transferred to the ICU or recovery area for close observation and regular laboratory testing, but this decision is usually made by the team on a case-by-case basis.
Graft and recipient outcomes in living donation
Because recipients are in a relatively good clinical condition when they receive their transplant, and the surgery is performed at the most propitious time for both recipient and donor, the chances of an excellent outcome are thought to be high. However, early reports in the USA showed inferior results, attributed to problems with the selection and matching of donors to recipients, when compared with outcomes after DDLT.14 Subsequent studies undertaken by the Adult-to-Adult Living Donor Liver Transplantation Cohort Consortium (A2ALL), a group of nine high-volume liver transplant centres in the USA performing LDLTs, revealed generally favourable results across participating centres, but it qualified these findings by identifying the collective experience of the centre (>30 cases in total) as an important factor for success.15 Multiple single-centre studies have since shown results consistent with the notion that LDLT is as effective, if not better long term, than DDLT.4,5,16
Living donors
Living donor liver transplantation donors are healthy adults who take on the risk of a major surgical procedure for no intrinsic benefit to themselves. They may do so to help a friend, family member, or acquaintance – directed donation – but some make the decision to donate anonymously with the recipient not knowing the donor's identity – so-called altruistic or anonymous donation. This means that there is enormous pressure on the transplant centre to minimise all potential risks to the donor whilst being able to perform a life-saving transplant for the recipient. This risk mitigation relies heavily on careful donor selection, which is a detailed, protocolised, and time-consuming process (Table 2). The decision to accept a donor is made by a committee representing all the following hospital services and specialties:
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(i)
Hepatology
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(ii)
Transplant surgery
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(iii)
Anaesthesia
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(iv)
Transplant nursing
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(v)
Social work
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(vi)
Psychology/psychiatry
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(vii)
Nutrition
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(viii)
Pharmacy
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(ix)
Radiology
Table 2.
Evaluation process used to screen potential living donors for liver transplantation.
| Stage | Investigations | Actions and details |
|---|---|---|
| Initial screening for suitability | Age Blood type BMI |
Assign an ILDA:
|
| Medical evaluation | History and physical examination Blood tests Specialty team evaluations
ECG Urinalysis |
Blood tests:
|
| Infection screening | Infectious disease screening:
|
|
| Cancer screening | Age and sex appropriate cancer screening:
|
|
| Cardiovascular screening | Based on positive cardiovascular risk factors:
|
|
| Imaging | Volumetric and anatomical assessment:
|
|
| Follow up (if indicated) | Liver biopsy:
|
|
| Presentation to donor selection committee | Successful applicants are designated a donor candidate |
AIH: autoimmune hepatitis; CMV: cytomegalovirus; CXR: chest X-ray; EBV: Epstein-Barr virus; HAV: hepatitis A virus; HSV: herpes simplex virus; PBC: primary biliary cholangitis; PSC: primary sclerosing cholangitis; TB: tuberculosis; TSH: thyroid-stimulating hormone.
An extra layer of protection for the patient is provided by an independent living donor advocate (ILDA), whose important role is to provide unbiased information to the potential donor, recognising that most of the groups involved in the selection process thus far have a relationship with the transplant centre, the recipient, or both. The ILDA must ensure that the donor is not under any undue pressure to donate and can make a fully informed decision to undergo or withdraw from the procedure at any time.17
Exclusion criteria for donors are centre-specific but informed by regulations from national organ procurement organisations (e.g. the Organ Procurement and Transplantation Network in the USA and NHS Blood and Transplant in the UK). Common exclusion criteria include18:
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(i)
Age <18 yrs old
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(ii)
Age >60 yrs old
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(iii)
Inability to provide informed consent
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(iv)
Untreated malignancy
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(v)
Some active and latent infections
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(vi)
HBV, HCV, human immunodeficiency virus (HIV)
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(vii)
Active psychiatric disease
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(viii)
Thrombophilic disorders
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(ix)
Alpha-1-antitrypsin deficiency
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(x)
Obesity (body mass index >30)
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(xi)
Excessive steatosis on biopsy
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(xii)
Previous abdominal surgery
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(xiii)
Prediction of inadequate native liver remnant volume (<30%)
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(xiv)
Suspicion of ethics violation (coercion or payment)
Exclusion criteria i, ii, ix, x, xi and xii are based on recipient need and timeframe; these criteria may be modified.
Exclusion criterion v: for example cytomegalovirus, Epstein-Barr virus, tuberculosis, syphilis, toxoplasmosis, strongyloidiasis, geography-related endemic diseases.
Surgery for the donation procedures
The donor and recipient procedures are undertaken simultaneously by separate surgical and operating teams. The donor's procedure is usually started first, with the recipient's procedure following shortly after. This allows the resolution of any unexpected donor anatomy problems before the recipient's procedure reaches the point of no return.
The three most common LDLT procedures are right lobe hepatectomy, left lobe hepatectomy, and left lateral segment hepatectomy. More recently, centres have used advanced laparoscopic and robotic surgery programmes with encouraging results.19,20 The procedure choice depends on the surgical team's experience, suitability of the anatomy, and recipient's requirements. The donor procedure consists of five stages: cholecystectomy (and cholangiography for right lobe hepatectomy), liver mobilisation, isolation of hilar structures, parenchymal dissection, and finally, division of vessels and bile duct.21 The parenchymal transection is ultrasound-guided and performed with communication with the surgical team of the recipient at all times to ensure efficient merger of procedure end-points. After removal from the donor, the graft is flushed with preservative solution and placed on ice to reduce ischaemic injury whilst it undergoes back-table inspection and reconstruction of the venous outflow, hepatic artery and biliary anastomoses.21
Anaesthesia for living donors
As the LDLT donor is healthy and undergoes a high-risk procedure for no personal benefit, the focus of the anaesthetist is on mitigating risk and excellent pain control. A balanced technique using either a volatile agent or TIVA technique is acceptable. Invasive monitoring (with the use of arterial and central venous catheters) may be used depending on local protocols and practice. Although arterial waveform-based indices have been shown to be useful in guiding fluid therapy, there is currently no evidence that these techniques improve the outcome for the donor or the graft. A donor hepatectomy is a major abdominal procedure and care must be taken to manage central venous pressure to assist with the surgical dissection. Predonation, normovolaemic autologous haemodilution, and the use of cell salvage may reduce the need for allogeneic blood transfusion. Much attention is paid to perioperative pain management with the aim of maximising pain control with limited use of opioids. Frequently, a multimodal approach is adopted. This is often centre-specific and uses a variety of analgesics including gabapentinoids, non-steroidal analgesics, intravenous opioids, ketamine, lidocaine, dexmedetomidine, and regional anaesthesia techniques. The use of epidural catheters for postoperative pain management remains controversial because of the risk of post-resection coagulopathy and the fear of subsequent epidural haematoma formation.22 Postoperative hypocoagulability seems to be most pronounced on postoperative Day 2 or 3 but resolves soon afterwards.23 Even so, some centres advocate their use whereas others remain unconvinced and other regional anaesthesia procedures (e.g. intrathecal morphine, transversus abdominus plane, erector spinae or rectus sheath plane blocks) are available and pose less risk while reducing pain in the immediate postoperative period.24
Donors are usually admitted to the ICU after surgery, but this stay is not usually of any major duration or real clinical necessity.
Outcomes for living donors
Regeneration of the liver takes place rapidly after hepatectomy, with studies showing most growth occurring in the first 2 weeks after surgery, after which a continuing, albeit at a slower rate, increase in liver mass in the first year. By 3 months, donors can be expected to have ∼80% of baseline liver mass and after a year, close to 90%.25,26 Laboratory tests such as the international normalised ratio and bilirubin concentrations, seen as surrogates for synthetic and metabolic liver function, return to near-normal values by 3 months.25 However, some blood indices such as the platelet count take longer to normalise.27
The mortality rate for living liver donors is <0.5% and the incidence of near-miss events leading to serious but temporary disability (e.g. reoperation, sepsis, thrombosis, haemorrhage, respiratory failure) is ∼1%.28 A worldwide survey found the total complication rate after living liver donor surgery to be ∼24%.28 Most complications were self-limiting and resolved within a year, although some necessitated a readmission to the hospital for further treatment. Donors generally stay in the hospital for approximately a week, are back to work within 3 months and are fully recovered by 6 months.29 Long-term follow up to determine the effects of donation on living donors' psychological health has found that in general, they are happy to have donated and would do so again if asked.30
Special considerations
Altruistic or anonymous donation
Directed donation to a known recipient from within the circle of family and friends is widely accepted, as there is presumed to be some connection or relationship that may offset the risks of having surgery. However, it raises some concerns when someone willing to undergo those same risks for a recipient with whom there is no personal relationship.
The number of people coming forward to participate in living liver donor programmes has been increasing over the last decade, and the potential for these grafts to mitigate the shortage of donor organs is worth exploring further. Not all programmes undertake altruistic donation and vastly more candidates contact programmes and get to the screening process than become actual living liver donors. Donors are often well educated to university level, are of middle income, and come with a history of previous altruistic acts.31 Some have even donated tissue or an organ before.
The screening process is essentially the same as that for directed donation, except there is a greater focus on donor motivation and financial concerns. Donors often get to select which type of donor they wish to donate to (adult or paediatric), but programmes try to choose recipients based on medical need.32
Expedited evaluation for living liver donation
Occasionally, patients present as a medical emergency needing a liver transplant. Rapid decompensation of ESLD, acute hepatic failure, and trauma are examples of when prompt access to a donor organ is needed. Some of these patients can wait a short period for a deceased donor organ, but rarely, an urgent living donor graft may be the only option.
Whilst the donor's safety is paramount, there are few options available for the recipient and evaluation needs to be expedited.33 Most tests can be performed in a 24-h period, and surgery performed shortly afterwards.34 However, there is a question regarding the ability to obtain informed consent because the timeframe is insufficient for appreciation of the risks involved in becoming a donor. The usual donor selection process has inherent, built-in delays, which give potential donors time to process the information. Pressure is also placed on the transplant team to accept the donor offer and therefore presents more opportunities for mistakes.35 The ultimate goal is to ensure that the donor is not harmed physically or mentally, whilst procuring a life-saving organ for a dying patient.
Conclusions
Living donor liver transplantation may not be the panacea for the lack of suitable donor organs in Western societies, but it is a well-accepted option across Asia and the Middle East and is increasingly being performed in the West. In the short term, LDLT is at least as successful as DDLT and when looking longer term, may have better sustained outcomes.36 It also provides more flexibility for expedited cases. However, the main focus must remain on the continuing welfare of the donor.
Acknowledgements
The authors thank Christine Burr (Scientific Writer, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA) for her editorial assistance with the manuscript, Jaime Cisek (Living Donor Coordinator) for her insights into the selection process, and Jack Dong MD for the illustrations.
Biographies
Adrian Hendrickse MMEd MAcadMEd FRCA is an associate professor of anaesthesiology, medical director of abdominal organ transplant anaesthesiology, and programme director of the liver transplant anaesthesiology fellowship at the University of Colorado, Anschutz Medical Campus. His other interests are regional anaesthesia and simulation in education.
Justin Ko MD PhD is a professor of anaesthesiology at Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. He is director of International Affairs at the Korean Society of Transplantation Anesthesiologists (KSTA). His clinical interests are liver transplant and regional anaesthesia.
Tetsuro Sakai MD PhD is a professor of anaesthesiology and perioperative medicine at the University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. He is also a professor at the Clinical & Translational Science Institute at the University of Pittsburgh School of Medicine. His clinical focus is anaesthesia for liver transplantation but he is also interested in faculty development.
Matrix codes: 1F05, 2A07, 3A04
Declaration of interests
The authors declare that they have no conflicts of interest.
MCQs
The associated MCQs (to support CME/CPD activity) will be accessible at www.bjaed.org/cme/home by subscribers to BJA Education.
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