Toggle navigation menu
The Light is an initiative by the Sri Lanka College of Paediatricians aimed at advancing paediatric knowledge in Sri Lanka, benefiting both healthcare professionals and the general public.44/1, Gnanartha Pradeepa Mawatha, Last Modified May 9th, 2025
Acute liver failure (ALF) is an emergency condition characterized by extensive hepatic necrosis and severe hepatic dysfunction. Paracetamol overdose is the commonest cause for ALF. While viral infections, autoimmune liver disease and Wilson disease being known causes of paediatric ALF, at nearly half of the occasions, the cause of ALF remains unknown.
Prompt diagnosis & medical treatment with meticulous supportive care would assist liver regeneration and offer cure from ALF. Liver transplant (LT) is the only cure for medically refractory ALF.
Definition of acute liver failure is given below.
As diagnosing hepatic encephalopathy is challenging in young children, presence of encephalopathy is not an essential criterion to diagnose ALF. Onset of acute liver failure should be within 8 weeks from the onset of the liver disease.
The pathophysiology of ALF involves complex interactions between hepatocyte injury, immune activation, and systemic inflammation. The hallmark features of acute liver failure is hepatocellular necrosis with acute severe cell loss. The release of pro-inflammatory cytokines and damage-associated molecular patterns (DAMPs) from necrotic hepatocytes activates both innate and adaptive immune responses, exacerbating liver injury. This immune activation impairs hepatocyte regeneration and disrupts normal liver function. Coagulopathy arises due to the liver’s compromised ability to synthesize clotting factors, while elevated ammonia levels contribute to hepatic encephalopathy and cerebral oedema. Metabolic disturbances, including hypoglycaemia and lactic acidosis, further complicate the clinical picture.
Infectious agents
Herpes simplex virus 1 & 2, Enterovirus, Parvovirus, Adenovirus, Hepatitis A, B, D, E, Dengue, Epstein-Barr Virus, Cytomegalovirus, Escherichia Coli, Acinetobacter
Drugs
Paracetamol, Isoniazid, Rifampicin, Dapsone, Sodium Valproate, Carbamazepine, Methotrexate, Halothane, Herbal medications
Metabolic Syndromes
Wilson disease, Galactosemia, Tyrosinemia, Urea cycle defects, Bile Acid Synthesis defects, Neiman-pick Disease Type C, Hereditary fructose intolerance, Mitochondrial disease
Vascular/Ischaemic
Ischemia / circulatory shock
Autoimmunity
Autoimmune hepatitis
Other
Hemophagocytic lympho-histiocytosis, Gestational alloimmune liver disease, Seronegative hepatitis, Recurrent acute liver failure syndrome , Malignancy, Hemangiomas / AV malformations
Key features to be considered in the history
Physical signs to look for
| Grades | Clinical manifestations | EEG changes |
|---|---|---|
| I | Reversed sleep-wake cycle, mild intellectual impairment | Minimal |
| II | Drowsiness, asterixis, abnormal behaviour | Generalized slowing |
| III | Confused, hyperreflexia | Grossly abnormal slowing |
| IV | Unconscious, decerebrate or decorticate posture | Appearance of delta waves, decreased amplitudes |
Investigations of acute liver failure would include,
Bedside blood glucose is extremely important as hypoglycaemia (capillary blood sugar < 60 mg/dl) is known to occur with acute liver failure and needs prompt correction. Clotting profile plays a major role in diagnosing acute liver failure. The rest of the liver blood tests such as AST, ALT, GGT, ALP, albumin, bilirubin with split fractions provides hints for the diagnosis and help to appreciate the severity of the liver injury. Venous blood gas levels are crucial to look for the presence of acidosis and the metabolic status of the body. Specific investigations should be performed looking for the underlying aetiology depending on the age-related differential diagnosis. The summary of the investigations is depicted in the table below.
| Indication | Investigation |
|---|---|
| To diagnose ALF and to assess the liver status | AST/ALT/GGT/ALP Serum Total Bilirubin/ Direct Bilirubin Albumin Clotting profile – PT/INR, APTT, Fibrinogen, ROTEM Serum Ammonia levels |
| To assess the metabolic status of the body and organ involvement | Blood sugar Blood gas – HCO3, BE, Lactate Blood Urea, Serum Creatinine Serum Electrolytes – Na, K, Ca, Mg, PO4 EEG, CT |
| Infections – HSV PCR, Hepatitis Screening, Enteroviral PCR, Parvoviral screening Paracetamol / Toxins – Paracetamol levels, Other specific drug levels Autoimmune liver Disease – IgG, Autoantibodies, liver biopsy Wilsons disease – Ceruloplasmin, serum copper, eye assessment, urinary copper excretion, liver biopsy, genetics AFP – Tyrosinaemia / GALD Other metabolic liver diseases – Ammonia, Amino-acids, organic acids, acylcarnitine, urinary sugar, fatty acids, genetics GALD – Ferritin, AFP, Lip biopsy, T2 MRI liver Mitochondrial Diseases – Lactate, MRS, Muscle biopsy, genetics Indeterminate with aplastic anaemia – bone marrow biopsy | |
| Other investigations | FBC CRP Blood culture, Urine Culture CXR DT |
The most important and the crucial part of managing a child with ALF is the diagnosis. Once the diagnosis of ALF is made; the treatment of acute liver failure is broadly categorised into three main arms. Namely,
General management and the supportive care for a child with ALF is summarised here.
Specific Management
Regular monitoring is crucial in a child with acute liver failure in order to aid recovery and to avoid complications.
Liver transplant is the ultimate cure for medically refractory ALF. It is beneficial to discuss all children who meets criteria for ALF with a paediatric liver transplant centre at an early stage as the need for LT may arise at any time. King’s Wilson index is helpful in patients with suspected Wilson disease in listing for LT.
While emergency liver transplant offers rapid cure for medically refractory ALF, it presents challenges in arranging the team and logistics along with finding a liver donor. Hence, early referral to a liver transplant centre is crucial while being medically managed.
At present, Colombo North Centre for Liver Diseases offers emergency liver transplant service for children in Sri Lanka.
Outcomes of ALF vary. In developing countries with limited access to advanced medical care often leads to high rate of mortality. Some patients with ALF recover with supportive care, or with medications while others require liver transplantation.
Acetaminophen induced liver failure carries a good prognosis if NAC is commenced early, and the transplant free survival is higher compared to other aetiologies. Wilson disease presenting with encephalopathy would often require liver transplantation.
New advances
References
Authors details and affilations:
Dr Meranthi Fernando
Senior Lecturer & Honorary Consultant Paediatrician
Colombo North Centre For Liver Diseases & Dept of Paediatrics, FOM, University of Kelaniya, Colombo North Teaching Hospital, Ragama
Professor Rohan Siriwardana
Professor in hepatobiliary surgery & consultant gastroenterological surgeon
Colombo North Centre For Liver Diseases & Dept of Surgery, FOM, University of Kelaniya, Colombo North Teaching Hospital, Ragama