Fulminant hepatitis A in Indigenous children in north Queensland

Jeffrey N Hanna, Tim H Warnock, Ross W Shepherd and Linda A Selvey
Med J Aust 2000; 172 (1): 19-21.
Published online: 3 January 2000
Notable Cases

Fulminant hepatitis A in Indigenous children in north Queensland

Jeffrey N Hanna, Tim H Warnock, Ross W Shepherd and Linda A Selvey

Since 1993, three Indigenous children in north Queensland have died of fulminant hepatitis A. Even if the children had been able to undergo liver transplantation, prolonged immunosuppressant therapy and the likelihood of opportunistic infections would inevitably have jeopardised any chance of long-term survival. As hepatitis A has become a leading infectious cause of death in young Indigenous children in north Queensland, hepatitis A vaccine has recently been introduced into the vaccination schedule for these children.

MJA 2000; 172: 19-21
For editorial comment, see McCaughan & Torzillo

Introduction - Clinical record 1 - Clinical record 2 - Clinical record 3 - Discussion - Acknowledgement - References - Authors' details
- - More articles on Aboriginal health

Introduction Fulminant hepatitis A is rare in children, and most recent reports have been from developing countries.1-4 Occasional cases in children from industrialised countries tend to be in those who have recently travelled to hepatitis A endemic areas5,6 or who live in conditions of considerable socioeconomic disadvantage.7

We describe three cases of fulminant hepatitis A in Indigenous children in north Queensland, all of whom died. This uncommon but serious manifestation of a relatively common infection in Indigenous children presents major difficulties in clinical management,8 illustrating the importance of preventive public health measures.

Clinical record 1 A 4.5-year-old Torres Strait Islander boy, who had previously been in good health, presented to a local health centre in early 1993 with anorexia, dark urine and jaundice of several days' duration. Vomiting and irritability persisted for five days, and he was evacuated to Thursday Island Hospital. Two days later, he had a generalised seizure and became semi-comatose after an episode of haematemesis, and was evacuated to Cairns Base Hospital.

On admission in Cairns, the boy was deeply jaundiced, with hepatic fetor and moderate hepatomegaly. He did not respond to painful stimuli, and was generally hypertonic with upgoing plantar reflexes. He had raised serum bilirubin and liver enzyme levels, markedly elevated serum ammonia level, hypoglycaemia and a bleeding diathesis (see Box). He was positive for hepatitis A IgM, confirming acute hepatitis A; subsequent serological tests were negative for hepatitis B and C, cytomegalovirus (CMV) and herpes simplex virus (HSV) infection.

The boy was stabilised, placed on ventilator support and transferred the next day to the Royal Children's Hospital in Brisbane for consideration of liver transplantation. However, on arrival in Brisbane, he had fixed, dilated pupils, and urgent computed tomography showed gross cerebral oedema. Despite intensive treatment, his condition deteriorated, and he died the next day, nine days after initial presentation.

Postmortem examination showed massive hepatic necrosis and diffuse hypoxic ischaemic brain injury, secondary to cerebral oedema and raised intracranial pressure.

Clinical record 2 A 4.5-year-old Aboriginal girl was admitted to a community hospital near Townsville in late 1997 with fever, lethargy, dark urine and jaundice of uncertain duration. Apart from a persistent tinea capitis infection, she had been in reasonably good health. Four months before the current illness, she had been treated with a four-week course of ketoconazole, and results of liver function tests were normal at that time.

On admission, she had raised serum bilirubin and liver enzyme levels (Box). Serological tests confirmed acute hepatitis A; subsequent tests were negative for hepatitis B and C, CMV, HSV and Epstein-Barr virus infection. Four days after her admission, the girl's family took her from the hospital, and on her return the next day she was delirious. She was transferred to Townsville General Hospital.

On admission in Townsville, she was deeply jaundiced and irritable, with a depressed level of consciousness and moderate hepatomegaly. Peripheral reflexes were brisk, with up-going plantar reflexes and bilateral ankle clonus. Her serum bilirubin level had risen further (Box), she was hypoglycaemic, had a bleeding diathesis, and soon became hypokalaemic (serum potassium level, 2.7 mmol/L [RR, 3.5-4.5 mmol/L]). Several hours after admission, she had an episode of profound hypotension (systolic pressure, 50 mmHg) after aspiration of a large volume of bloodstained fluid from the nasogastric tube.

She was transferred the next day to the Royal Children's Hospital in Brisbane for consideration of liver transplantation. On arrival in Brisbane, her serum ammonia and sodium levels were both markedly elevated (ammonia, 158 µmol/L; sodium, 151 mmol/L [RR, 133-143 mmol/L]). Computed tomography showed cerebral oedema with a possible ischaemic lesion in the right cerebral hemisphere. She was listed for urgent liver transplantation pending a suitable donor, but the next day developed signs of raised intracranial pressure which did not respond to medical management. She died eight days after initial presentation.

Clinical record 3 A 2.5-year-old Aboriginal girl, who had previously been in good health, presented to a health centre in a Cape York community in September 1998 with malaise and jaundice of one day's duration. She was reviewed the next day by the visiting Royal Flying Doctor Service; a clinical diagnosis of acute hepatitis was made, but, because she did not appear particularly unwell, no specific treatment was requested. Liver function tests on that day (Day 2) showed her serum concentrations of bilirubin, AST and ALT were raised (Box). Serological testing confirmed acute hepatitis A, and tests for hepatitis B and C were negative.

The girl was reviewed two days later by health centre staff. She reportedly had stopped eating and appeared lethargic, although she responded appropriately to voices and other stimuli. When seen the next morning, she had deteriorated markedly, no longer responded to her environment and was obtunded and dehydrated, with grunting respirations. She was evacuated urgently to Cairns Base Hospital.

On admission in Cairns she was deeply jaundiced, with hepatic fetor and mild hepatomegaly. She was semi-comatose, had brisk symmetrical reflexes and upgoing plantar reflexes. Her serum ammonia level was markedly raised and she had a bleeding diathesis (Box). Urgent transfer to Brisbane was arranged, but she deteriorated nine hours after admission with extensor posturing and diminished respiratory effort; her limbs subsequently became flaccid and areflexic. She died several hours later, five days after initial presentation.

Discussion All three of the reported children were critically ill with fulminant liver failure and grade III hepatic encephalopathy9 when referred to specialist services in Cairns or Townsville. Mortality rates in fulminant hepatitis approach 70% in children,8 with death usually occurring within 8-10 days. Youth and severity of hepatic encephalopathy are both strong predictors of poor outcome;10 the main cause of death is cerebral oedema.10

Liver transplantation is the only option for children with fulminant hepatitis A and advanced stages of encephalopathy who are considered unlikely to survive with medical supportive therapy alone.6,8-10 Published criteria for transplantation include either PT > 100 s or any three of the following: PT > 50 s, age < 10 years or > 40 years, jaundice for > 7 days before onset of encephalopathy, or serum bilirubin > 300 µmol/L.11 However, in practice, the availability of a suitable donor organ may be the critical issue, and therefore most transplant centres list patients as soon as transplantation is considered, and make a final decision if and when a donor organ becomes available.8 Two of the children (Patients 1 and 2) clearly met the above criteria and were listed for urgent transplantation on arrival in Brisbane, but it soon became apparent that irreversible brain damage had occurred. However, even if they had received a successful liver transplant, the difficulties of monitoring prolonged immunosuppressant therapy and the likelihood of opportunistic infections in their home communities would have inevitably jeopardised any chance of long-term survival.

Hepatitis A has been the most frequent infectious cause of death in preschool-aged Indigenous children in north Queensland since 1993 (excluding neonatal deaths and pneumococcal infections, for which data are incomplete) (J Hanna, unpublished data). Two deaths resulted from the "standard" vaccine-preventable diseases (measles and Haemophilus influenzae type b infection), and one from meningococcal infection. Over the same period, no non-Indigenous children died of hepatitis A in north Queensland. We can only speculate that "host factors", as well as the quantity of viral inoculum,6 may determine why some Indigenous children develop fulminant hepatitis A.

The notification rates of hepatitis A in children under five years of age in north Queensland in 1996-1997 were 264 and 10 per 100 000 in Indigenous and non-Indigenous children, respectively.12 About 25% of notified cases of hepatitis A in Indigenous people in north Queensland occur in children under five years of age,12 indicating considerable circulation of the hepatitis A virus among these young children. However, nearly half the notified cases in Indigenous people in north Queensland occur in children aged 5-14 years,12 indicating that many Indigenous primary school-aged children are susceptible to the infection. Very few notifications are in Indigenous adults over 30 years of age.

Because hepatitis A is common in Indigenous children in north Queensland, and because of the demonstrated unsatisfactory outcome in those few children who develop fulminant liver failure, the emphasis must be on preventing infection.

Hepatitis A virus is readily transmitted in environments with inadequate sanitation and water supply, suboptimal hygiene and overcrowding.13 The current status of housing and environmental health infrastructure throughout Indigenous Australia has recently been detailed elsewhere, and others have described some of the health consequences of these circumstances.14,15 Despite considerable recent improvements in provision of adequate housing and sanitation infrastructure in several Indigenous communities in north Queensland, many communities still have unresolved problems of overcrowding, water supply and waste disposal.16 Some communities continue to experience environmental contamination by raw sewage during wet season floods, and several Torres Strait Island communities experience severe water shortages in the dry season.17

Some of these problems are likely to persist for the foreseeable future. Paradoxically, as environmental circumstances improve, the age of reported patients will likely shift upwards, and the "visibility" of hepatitis A -- and public health concern -- will increase.13 Indigenous communities in North America have experienced cyclical outbreaks of hepatitis A every 5-10 years for many years,18 a pattern that may become more obvious in Indigenous Australian communities.

Inactivated vaccines with proven effectiveness in preventing hepatitis A in children19,20 have recently become available in Australia. These vaccines have also been shown to interrupt transmission in "closed" communities prone to recurrent outbreaks,21,22 leading to the recommendation of routine hepatitis A vaccination for Indigenous children in North America.18

An inactivated hepatitis A vaccine has been offered to Indigenous children in north Queensland since early 1999. Two doses six months apart have been recommended, integrated as far as possible into the standard vaccination schedule, with the first dose at 18 months of age and the second at 24 months, necessitating only one "extra" visit to a vaccination service. Current resources allow for catch-up hepatitis A vaccination up to the sixth birthday; about 5500 Indigenous children aged 2-5 years live in north Queensland.

Young children play a particularly important role in maintaining transmission of hepatitis A virus to older susceptible individuals during community-wide outbreaks,24 because of their lack of bowel control and attention to hygiene, and need for adult supervision of their toileting needs. Therefore, vaccination of preschool-aged Indigenous children provides a means not only to prevent further cases of fulminant hepatitis A in Indigenous Australian children, but also to reduce the extent of future outbreaks in their communities. A particular challenge will be to ensure that Indigenous children in rural towns and urban settings gain access to the vaccine.25

Acknowledgement We wish to thank the families of the three children for allowing us to describe their children's final illness.

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(Received 6 Apr, accepted 24 Aug, 1999)

Authors' details Queensland Health, Cairns, QLD.
Jeffrey N Hanna, MPH, FAFPHM, Public Health Physician, Tropical Public Health Unit;
Tim H Warnock, FRACP, Paediatrician, Cairns Base Hospital.

Department of Gastroenterology and Hepatology, Royal Children's Hospital, Brisbane, QLD.
Ross W Shepherd, MD, FRACP, Director.
Communicable Diseases Unit, Queensland Health, Brisbane, QLD.
Linda A Selvey, PhD, FAFPHM, Manager.

Reprints will not be available from the authors.
Correspondence: Dr J N Hanna, Tropical Public Health Unit, Queensland Health, PO Box 1103, Cairns, QLD 4870.

Results of investigations of three Indigenous children with fulminant hepatitis A
Patient 2
Patient 3
Patient 1
On admission
Day 5
Day 2
Day 5

Serum bilirubin level (µmol/L)
Aspartate aminotransferase level (U/L)
Alanine aminotransferase level (U/L)
Blood glucose level (mmol/L)
Prothrombin time (s)
Activated partial thromboplastin time (s)
Serum ammonia level (µmol/L)

ND = not done
  • Jeffrey N Hanna
  • Tim H Warnock
  • Ross W Shepherd
  • Linda A Selvey



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