Acute liver failure: SAQ

This girl presents acute liver failure. The international normalised ratio of 3.2 with lethargy meets the paediatric definition, the falling arterial pH of 7.29 signals accumulating acid and failing clearance, and the hypoglycaemia, raised ammonia, and hepatomegaly complete the picture of massive hepatocyte loss with failing synthetic and detoxifying function. The preceding viral illness raises a viral or metabolic cause, but the immediate priority is resuscitation in parallel with the workup and early referral to a transplant centre. [1]

Question 1 (10 marks)

Outline your immediate resuscitation and diagnostic approach to this child, including how you confirm the diagnosis and the investigations you would arrange. [1]

I would first secure the airway, breathing, and circulation, establish intravenous access, and treat the hypoglycaemia immediately with an intravenous dextrose bolus followed by a continuous dextrose infusion at 6 to 8 milligrams per kilogram per minute of glucose, titrated to normoglycaemia with frequent bedside glucose checks, because the failing liver cannot perform gluconeogenesis and untreated hypoglycaemia worsens encephalopathy. I would manage the coagulopathy with restraint, reserving fresh frozen plasma for active bleeding or before procedures such as central line insertion, and giving vitamin K, because the international normalised ratio is the most important prognostic trend and prophylactic products mask it. [1]

The diagnosis is paediatric acute liver failure, confirmed by an international normalised ratio of 1.5 or greater with any encephalopathy, or 2.0 or greater without encephalopathy, in a child without chronic liver disease. Her international normalised ratio of 3.2 with lethargy meets this definition. I would start N-acetylcysteine empirically, with a loading dose of 150 milligrams per kilogram over 60 minutes, then 50 milligrams per kilogram over 4 hours, then 100 milligrams per kilogram over 16 hours, because it is recommended for non-acetaminophen acute liver failure in children with coagulopathy while the cause is sought. [3]

I would arrange a comprehensive cause-directed workup in parallel: an acetaminophen level; autoimmune markers including antinuclear antibodies, anti-smooth muscle antibodies, and immunoglobulin G; a viral screen including hepatitis A, B, and E serology, Epstein-Barr virus, and herpes simplex virus polymerase chain reaction given the preceding illness; and a metabolic screen including ammonia, lactate, ceruloplasmin, urinary copper, alpha-1 antitrypsin phenotype, and urinary reducing substances. An abdominal ultrasound with Doppler would assess the liver, biliary tree, and hepatic vascular patency. I would monitor serial international normalised ratios, arterial blood gases, ammonia, renal function, and electrolytes, and arrange urgent transfer to a paediatric liver transplant centre. [1]

Question 2 (10 marks)

Describe how you would decide whether this child needs liver transplantation, and explain the limitations of the King's College Criteria in this decision. [2]

The decision to list for liver transplantation is the most consequential judgement in acute liver failure, and in children it is made on the basis of dynamic trends rather than a single adult score. I would track the trend in the international normalised ratio, the depth and progression of her encephalopathy, the arterial pH and lactate, and the development of renal and other organ dysfunction. A child who is worsening on maximal medical therapy, with a rising international normalised ratio, deepening encephalopathy, a falling arterial pH, and emerging multiorgan failure, is listed urgently. [2]

The critical limitation is that the King's College Criteria, developed by O'Grady and colleagues in 1989 for adult fulminant hepatic failure, are not validated in children and perform poorly in paediatric cohorts. For paracetamol cases they use an arterial pH below 7.3 or a composite of international normalised ratio, creatinine, and encephalopathy, and for non-paracetamol cases the international normalised ratio or a composite of age, bilirubin, cause, and jaundice duration. Applying these rigidly to children risks both errors: denying transplant to a deteriorating child who does not meet the adult thresholds, and listing a child who meets them but is actually recovering. [2]

The paediatric approach is therefore dynamic and multidisciplinary. The Paediatric End-stage Liver Disease score and other dynamic markers inform the urgency, and the decision is made jointly by the paediatric hepatology, intensive care, and transplant surgery teams at a specialist centre. The single most important principle is early referral to a transplant centre before multiorgan failure is established, because transfer after decompensation is often too late. Live donor liver transplantation is an option where a suitable donor is identified, particularly in regions with deceased donor shortage. If the cause proves to be treatable, such as autoimmune hepatitis responding to corticosteroids, the transplant may be averted, but the listing decision is made on trajectory, not on hope. [1]