Liver transplantation in children: SAQ

This boy with biliary atresia has developed the classic indications for liver transplantation after a failing Kasai: intractable pruritus, recurrent cholangitis, growth failure, and early synthetic dysfunction. The fall in his growth centile is itself a marker of disease severity that, uniquely in children, is built into the allocation score. The family's question about a living donor is timely, because the smallest children face the longest waits for a size-matched deceased organ. [10]

Question 1 (10 marks)

Outline the indications for liver transplantation in this child, describe how he would be prioritised on the deceased-donor waiting list, and discuss the role of living-donor transplantation. [1]

The accepted indications for transplantation in a child with a failing Kasai are synthetic failure (a falling albumin and rising international normalised ratio, which he shows with an albumin of 28 grams per litre and an international normalised ratio of 1.7), intractable pruritus that disrupts sleep and quality of life, growth failure despite nutritional support (his fall from the 25th to below the 3rd centile), recurrent cholangitis (his two episodes), and portal hypertension that is difficult to control. He meets several of these, and referral to a paediatric transplant centre is indicated. [10]

He would be prioritised on the deceased-donor waiting list by the Paediatric End-stage Liver Disease score, introduced for allocation in the United States from 2002. The score is calculated from five variables: serum bilirubin, the international normalised ratio, serum albumin, growth failure defined as height or weight less than two standard deviations below the mean, and age at listing, with additional weight given to age under one year. Growth failure is deliberately weighted because malnutrition reflects disease severity in children in a way that no adult variable captures, and his marked growth failure will raise his score and his priority. His bilirubin of 140 micromoles per litre, his international normalised ratio of 1.7, his low albumin, and his growth failure will all contribute to a high PELD score. [3]

I would counsel the family that living-donor transplantation is an established option in which a parent typically donates a left lateral segment. It was developed because the smallest infants have the highest waiting-list mortality, as size-matched deceased donors are scarce, and a living-donor graft shortens waiting time and reduces the risk of dying on the list. The donor evaluation is conducted to the same safety standards as a deceased-donor pathway, and the donor hepatectomy, while safe in experienced hands, carries a small but real morbidity and a rare mortality that must be disclosed. The trade-off is a higher vascular and biliary complication rate in the segmental graft, which I would discuss honestly. [1]

Question 2 (10 marks)

Two months after transplantation, this boy presents with fever and a raised alanine transaminase. Describe your diagnostic approach and your management of confirmed acute cellular rejection, including the principles of tacrolimus therapeutic drug monitoring. [8]

My diagnostic approach follows the temporal pattern. Two months after transplant, the differential for a rising transaminase and fever includes acute cellular rejection (the most common cause in the first month and still very relevant at two months), a biliary complication, infection, and vascular thrombosis. The first investigation is a Doppler ultrasound to confirm hepatic artery patency, 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 and graft loss. Once vascular patency is confirmed, the gold standard for acute cellular rejection is liver biopsy, which shows the triad of portal inflammation, bile duct damage, and venous endothelialitis, graded by the Rejection Activity Index. I would also send cultures, a cytomegalovirus and Epstein-Barr virus polymerase chain reaction, and review the tacrolimus trough. [8]

If biopsy confirms acute cellular rejection, I would treat with a high-dose corticosteroid pulse: intravenous methylprednisolone 10 milligrams per kilogram per day in divided doses for three days, followed by an oral steroid taper. The majority of episodes respond to a single pulse. I would repeat the biopsy if there is no biochemical and histological improvement, because steroid-resistant rejection escalates to a lymphocyte-depleting agent such as anti-thymocyte globulin. [8]

Throughout this episode I would manage tacrolimus by therapeutic drug monitoring of the whole-blood trough concentration. The target is 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: too little and the graft rejects, as may have happened here, and too much and the child develops nephrotoxicity, neurotoxicity, hypertension, and diabetes, and an increased susceptibility to opportunistic infection and Epstein-Barr-virus-driven post-transplant lymphoproliferative disorder. Tacrolimus has extensive drug interactions via CYP3A4 that must be checked with any new prescription. After a rejection episode, I would review adherence and the dosing schedule, optimise the trough, and plan a careful long-term wean to the lowest effective dose. [6]