On 31 March 2022, severe acute hepatitis in children of unknown cause (acute severe hepatitis of unknown etiology in children, ASHep-UA) was first reported in Scotland. Since then, such cases appeared in many countries or regions around the world, and the proportion of severe cases was relatively high, which attracted wide attention. Since 12 April 2022, the European Center for Disease Control and Prevention and the World Health Organization's (WHO) official website has published information about the disease several times. On April 23, 2022, the WHO issued the diagnostic recommendation, but there was no recommendation for the treatment plan due to the unknown etiology. No relevant cases have been reported in China. In order to effectively strengthen the early identification and standardized diagnosis and treatment of the disease, and to improve the treatment effect, the CPC Committee has formed the Guidelines for the Diagnosis and Treatment of Severe Acute Hepatitis in Children of Unknown Cause (Trial) according to relevant reports and literature and combined with the practice of hepatitis diagnosis and treatment.

Clinical manifestation Acute onset, mostly manifested as fatigue and poor appetite, nausea, vomiting, diarrhea, abdominal pain, and other digestive tract symptoms, followed by the appearance of urine yellow red, skin, and sclera yellow dye, some children can have white stool color, liver enlargement, fever, and respiratory symptoms, some may have the spleen enlargement. A few cases can progress to acute liver failure in a short time, with progressive aggravation of jaundice, hepatic encephalopathy, and other manifestations.

Therapeutic measure Comprehensive treatment measures based on symptomatic and supportive treatment should be taken, such that the changes in the condition should be closely observed, the mental state should be evaluated, and the laboratory indicators should be monitored to prevent complications. Patients with liver failure should be referred to hospitals.

l Treatment of hepatitis stage.

1. General treatment and nursing care: (1) Rest: reduce physical consumption and avoid strenuous exercise; jaundice, vomiting, fatigue, and tolerance. (2) Nutritional support: ensure calorie intake, give children a high-carbohydrate, low-fat, and high-quality protein diet, and supplement many vitamins. Those who eat insufficiently should take intravenous supplements. (3) Monitor the changes in the condition, actively correct hypoalbuminemia, hypoglycemia, water-electrolyte, and acid-base balance disorder, and be alert to complications such as liver failure.

2. Symptomatic treatment: choose liver protection drugs as appropriate, and use ursodeoxycholic acid in patients with cholestasis; pay attention to keeping the stool unobstructed, and constipation patients can use lactulose to reduce the absorption of the poison.

l Treatment of liver failure.

They can be transferred to the intensive care unit and given life support treatment under close care. Close collaboration with the multidisciplinary team contributes to improving patient survival. 1. Fluid therapy: the total amount of intravenous infusion should be limited, avoid the use of liquid containing lactic acid, adjust the glucose infusion rate according to the blood glucose level, maintain the electrolyte balance, and pay attention to correct the hypoalbuminemia. If circulatory instability occurs, fluid resuscitation should be given.

2. Hepatic encephalopathy and intracranial hypertension: keep the environment quiet; reduce unnecessary stimulation; careful use of sedative drugs; timely detection and treatment of factors that may aggravate the condition, including infection, shock, gastrointestinal bleeding, acute kidney injury, and hydroelectrolyte disorder; for patients with cerebral edema and intracranial hypertension, mannitol, hypertonic saline, and diuretics.

3. Hyperammonemia: when blood ammonia is significantly increased or accompanied by hepatic encephalopathy, the protein intake should be reduced to 1g / k g/d; oral or high enema should be given to promote defecation and reduce the absorption of intestinal ammonia; intravenous infusion of arginine, aspartate-ornithine to promote the excretion of ammonia; and branched-chain amino acids should be used as appropriate. If it is still ineffective or the blood ammonia is seriously increased, the blood purification treatment should be considered.

4. Coagulation dysfunction: intravenous vitamin K1 supplementation; fresh frozen plasma and/or platelets, and fibrinogen decrease (<1g / L); without active bleeding or invasive operation, it is not recommended to give blood products to correct coagulation abnormalities to avoid transfusion-related adverse reactions such as fluid overload.

5. Respiratory failure: when oxygen occurs, give the nasal catheter for oxygen, still not relieved or aggravated, and give non-invasive or invasive ventilation as appropriate.

6. Cardiovascular dysfunction: maintain effective circulating blood volume; in patients with blood pressure reduction, cardiac dysfunction can receive blood pressure and cardiac drugs to maintain appropriate blood pressure and improve myocardial contractility.

7. Acute kidney injury: reduce or stop using diuretics, avoid using nephrotoxic drugs, and maintain effective blood volume. Terlipressin or noradrenaline can be combined with albumin. Patients with severe oliguria or anuria, fluid overload, progressive increase of serum creatinine, and severe electrolyte and acid-base balance disorders may be given renal replacement therapy. 8. Control of secondary infection: When secondary infection is suspected, antimicrobial treatment should be started after retaining the relevant pathogen specimens, adjusted according to the culture and the drug sensitivity results, and the treatment should be stopped as soon as possible after infection control.

8. Extracorporeal liver supportive therapy: mainly used for severe coagulation abnormalities and hepatic encephalopathy that cannot be alleviated by conventional therapy, or as a transitional therapy before liver transplantation. Plasma exchange, blood perfusion, and plasma adsorption can be selected as appropriate.

10. Liver transplantation: For patients with severe liver failure who respond to medical treatment, a multidisciplinary team should be organized as early as possible to decide whether to undergo liver transplantation.