Liver transplantation in children: Viva

Branch 1: Indications, graft types, and waiting-list priority

The candidate should establish that biliary atresia is the single most common indication for paediatric liver transplantation, accounting for up to half of all cases, and that this infant with a failing Kasai is a classic candidate. A strong candidate lists the accepted indications: synthetic failure, intractable pruritus, growth failure despite nutritional support, recurrent cholangitis, and portal hypertension that is difficult to control. The candidate should also name the other major indication categories: metabolic and genetic disease, acute liver failure, chronic cholestasis and cirrhosis, and liver tumours. [1]

If the examiner asks about graft types, the candidate should explain why children rarely receive a whole-organ deceased-donor graft: the small size of the recipient and the scarcity of size-matched paediatric deceased donors mean that most children receive a segmental graft, whether reduced-size, split, or living-donor. The candidate should explain that a left lateral segment from a living donor, typically a parent, fits an infant and shortens waiting time, and that living-donor and split grafts were developed specifically because the smallest infants have the highest waiting-list mortality. The trade-off is donor morbidity and a higher vascular and biliary complication rate. [1]

The candidate must then describe the Paediatric End-stage Liver Disease score. It is calculated from five variables: serum bilirubin, the international normalised ratio, serum albumin, growth failure, and age at listing, with additional weight for age under one year. A strong candidate explains the paediatric insight that growth failure is deliberately weighted because malnutrition reflects disease severity in children in a way that no adult variable captures, and that the score prioritises children on the deceased-donor waiting list. The candidate should mention that standardised exception scores exist for conditions whose severity the raw score underestimates, such as metabolic disease and unresectable tumours. [3]

Branch 2: Maintenance immunosuppression

If the examiner moves to immunosuppression, the candidate should state that the keystone of long-term graft survival is a maintenance regimen anchored on a calcineurin inhibitor, almost always tacrolimus. The candidate should explain the mechanism precisely: tacrolimus binds FK-binding protein 12, the complex inhibits calcineurin, and without calcineurin-mediated activation of nuclear factor of activated T-cells, interleukin-2 transcription is blocked and T-cell proliferation stalls. This is why it prevents the CD8-mediated attack on bile ducts and endothelium that defines acute cellular rejection. [6]

The candidate must demonstrate command of therapeutic drug monitoring. Tacrolimus is monitored by whole-blood trough concentration, with a target around 8 to 12 nanograms per millilitre in the early months, weaning toward 4 to 6 nanograms per millilitre long term. The therapeutic window is narrow: subtherapeutic levels risk rejection, and supratherapeutic levels cause nephrotoxicity, neurotoxicity, hypertension, diabetes, and an increased susceptibility to infection and Epstein-Barr-virus-driven post-transplant lymphoproliferative disorder. A strong candidate mentions the extensive CYP3A4 drug interactions. Most regimens pair tacrolimus with a steroid taper and frequently mycophenolate mofetil, and the contemporary trend is toward steroid-sparing and steroid-free tacrolimus-basiliximab induction. [6]

If pressed on minimisation and tolerance, the candidate should explain the deliberate slow wean toward the lowest effective tacrolimus dose, and that a selected minority of stable children may achieve operational tolerance with complete immunosuppression withdrawal under specialist protocols, more so than in kidney or heart recipients. The candidate should be honest that a 10-year prospective study shows operational tolerance is not always permanent, so withdrawal remains a specialist, protocolised decision rather than routine practice. [8]

Branch 3: The rising transaminase — rejection, thrombosis, and PTLD

If the examiner pivots to a post-transplant child with a rising transaminase, the candidate must work through the differential in order of gravity. The first investigation is a Doppler ultrasound of the hepatic artery, because hepatic artery thrombosis cannot wait for a biopsy: the biliary tree is supplied exclusively by the hepatic artery, and arterial thrombosis produces ischaemic bile duct injury, bile leak, biliary strictures, and graft loss. The candidate should name the time course, the first days to weeks, and the need for urgent revascularisation or retransplantation. [8]

Once vascular patency is confirmed, the candidate should proceed to biopsy. Acute cellular rejection is the most common cause in the first month, and the biopsy shows the triad of portal inflammation, bile duct damage, and venous endothelialitis, graded by the Rejection Activity Index. First-line treatment is a high-dose corticosteroid pulse: intravenous methylprednisolone 10 milligrams per kilogram per day for three days with an oral taper. The majority respond, and steroid-resistant rejection escalates to anti-thymocyte globulin. [8]

If the examiner pushes to the late complications, the candidate should describe post-transplant lymphoproliferative disorder as Epstein-Barr-virus-driven B-cell proliferation that is most common in seronegative recipients. It presents with fever, lymphadenopathy, and a rising Epstein-Barr viral load, and ranges from reactive polyclonal proliferation to frank monoclonal lymphoma. The first step in management is reduction of immunosuppression to restore T-cell immune surveillance, with rituximab for refractory disease and chemotherapy for aggressive lymphoma. The candidate should close on the other long-term threats: calcineurin-inhibitor nephrotoxicity, de novo malignancy, and, above all, adolescent non-adherence, a leading preventable cause of late graft loss that makes structured adherence assessment and transition planning core management. [11]