The latest figures from the World Health Organization (WHO) show that 34 countries worldwide have reported about 700 cases of unexplained childhood hepatitis, with 112 more cases under investigation, including at least 38 WHO have had liver transplants and 10 WHO have died. At present, the cause of these cases is still under investigation, and the patients who progress to liver failure and require transplantation are the key clinical treatment.

Researchers from the Paediatric INTENSIVE CARE Unit at King’s College Hospital London (KCH) published an article entitled “Outbreaks of hepatitis in Children: Outbreak of hepatitis in children admitted to intensive care units Clinical course of children with acute liver failure admitted to the intensive care unit).

Source: Thepaper.cn

Of the eight children who developed liver failure in the Paediatric intensive Care unit at King’s College Hospital (KCH), six received liver transplants. Adenoviruses were detected in the whole blood of the eight children, but were not detected in the livers of the six children (liver transplant recipients) who had access to liver biopsies. Six of the eight children were infected with novel coronavirus (POSITIVE sarS-COV-2 antibody), accounting for 75% of the total. The researchers also note that it is important to note that sarS-COV-2 seroposiencies were 47% in people aged 1-4 and 67% in people aged 5-11 in January-February 2022, according to a 25 April technical briefing from the HEALTH And Safety Agency. The latest official information on seroprevalence in this age group is awaited.

The UK is the first country to report this wave of high-profile outbreaks of unexplained childhood hepatitis. On 5 April 2022, WHO was informed of 10 cases of severe acute hepatitis of unknown etiology in children under 10 years of age in central Scotland. Three days later, on April 8, the UK reported 74 cases. It is worth noting that paediatric liver disease services in the UK are concentrated in three centres, which is one of the reasons why more cases were first reported and quickly counted in the UK.

King’s College Hospital (KCH), which published this article, is the largest pediatric liver transplantation center in the world, and is also recognized as the origin of pediatric hepatology in the industry.

Outbreaks of acute non-A-E hepatitis with serum transaminases greater than 500 IU/L found in children under 16 years of age have become A major concern for public health authorities, paediatric liver and critical care services, the researchers note. From 1 January to 16 May 2022, public Health authorities in England reported 197 cases, with a median age of 3 years, evenly split between boys and girls, from all regions of the UK, and 11 children undergoing liver transplantation (LT).

Of these, eight children were admitted to the Paediatric Intensive Care Unit (PICU) at King’s College Hospital (KCH) between February and May 2022. All patients were younger than 5 years old except 1 patient. All patients were white. All children developed abdominal symptoms (diarrhoea and vomiting), followed by jaundice and elevated aminotransferases (ALT and AST> 2500 iu/L). In addition, the whole blood of these cases tested positive for adenovirus DNA.

Extensive screening for the virus was carried out on blood, urine, faeces and respiratory samples from all patients, as recommended by the UK Health Safety Agency (UKHSA). Two of these patients had a history of SARS-COV-2 8 weeks prior to onset. Six of the eight patients were positive for SARS-COV-2 antibody. However, all of these pediatric ICU patients tested negative for SARS-COV-2 by POLYMERase chain reaction (PCR) and were not vaccinated against COVID-19.

The researchers also note that it is important to note that sarS-COV-2 seroposiencies were 47% in people aged 1-4 and 67% in people aged 5-11 in January-February 2022, according to a 25 April technical briefing from the HEALTH And Safety Agency. The latest official information on seroprevalence in this age group is awaited.

The primary reason for these children’s transfer to the pediatric intensive care unit was neurological deterioration (hepatic encephalopathy) with elevated transaminase, lactic acid levels and international standardized ratio (INR). Alleged liver sex encephalopathy, because be urgent, chronic liver function is serious obstacle or all sorts of portal vein – body circulatory shunt is abnormal be caused by namely, with metabolization disorder is a foundation, the nerve spirit that weight degree differs is abnormal syndrome.

Neurological monitoring was performed using transcranial Doppler (TCD) and jugular vein saturation. Abnormal TCD pulsatile index was found in 4 cases, and jugular vein saturation was found in 6 cases (minimum 25.9%), requiring intervention.

To protect the nervous system, interventions included initiation of continuous renal replacement therapy (min. 60ml/kg/h), plasmapheresis, hypertonic saline, norepinephrine to maintain cerebral perfusion pressure, temperature control, and sodium thiopental injection at an early stage (within 24 h of admission to the hospital for PICU).

All patients were treated with n-acetylcysteine, and adenovirus-positive patients were treated with at least 2 doses of cidofovir.

How to evaluate whether these children need liver transplantation? The research team used INR> 4 as inclusion criteria. All 8 children admitted to the Paediatric intensive Care Unit at King’s College Hospital (KCH) (PICU) survived, 6 of whom required liver transplantation (1 was re-transplantation); Two patients ultimately survived without liver transplantation, one of whom was removed from the super emergency list after 6 days due to improved clinical and biochemical status, and the other patient was treated with methylprednisolone for positive antinuclear antibody.

The median wait time from being placed on the transplant list to liver transplantation was 3 days (range 1-6 days) and the median pediatric intensive care unit stay was 12 days (4-22 days). Longer hospital stays were associated with the use of neuroprotective measures, particularly deep sedation before and after transplantation, the researchers note. The liver immunohistochemistry of the 6 transplanted children was negative for adenovirus.

Investigations into the causes of cases in the UK have found a high incidence of adenovirus positivity, with current data showing 68 per cent of those tested positive, mainly from blood, the most common type 41F, the researchers said. However, histopathological studies of the liver of the six transplanted children and a few biopsies did not prove adenovirus presence in the liver cells, although all showed hepatocyte necrosis and parenchymal atrophy, the article notes.

Adenoviruses are absent in liver cells, but acute liver failure caused by severe liver injury may be associated with an abnormal immune response of the host liver immune system, the article said. The detailed characteristics of liver immune infiltration in children who progress to liver failure may identify subgroups that respond to immunosuppression (including steroids) and thus avoid liver transplantation.

The researchers also noted that speculation that the childhood hepatitis outbreak was related to SARS-COV-2 or the vaccine has not been confirmed. Adenovirus is present in these children, and one hypothesis is that it is mediated by a sarS-COV-2 superantigen enhanced by a second virus. At the same time, patients requiring emergency liver transplantation have abnormal immune responses. The 10% hypothesis is also being investigated.

The researchers concluded that pediatric critical care capacity is strained due to the limited number of donor organs. Therefore, it is particularly important to determine which patients should be listed for liver transplantation and which are likely to recover with supportive therapy.

They believe that most children with hepatitis can receive specialist counselling at a tertiary liver centre locally. However, for those who progress to acute liver failure, specialized intensive liver care is required. Early referral to a liver transplant center, early detection of neurological deterioration, early intervention, and close neurological monitoring and protection, as well as close collaboration with liver and transplant colleagues to determine the timing of treatment and transplantation in these patients, lead to relatively good clinical outcomes.

The King’s College Hospital (KCH) team finally points out that as our understanding of the mechanisms supporting these cases becomes clear, especially if immune-mediated, we may be able to manage these children with intensive care treatment in combination with steroids and other immune-modulating drugs.

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