Since March 2022, acute severe hepatitis of unknown aetiology in children (ASHep-UA) has been reported in many countries and regions around the world, and a high proportion of severe cases has attracted widespread attention. At present, the etiology of the disease is unknown, and there are no related case reports in my country. In order to prepare for medical treatment in advance, the National Health and Health Commission organized the formulation of the “Guidelines for the Diagnosis and Treatment of Severe Acute Hepatitis in Children of Unknown Cause (Trial)”. According to the “Guidelines”, On May 27, 2022, WHO announced that 33 countries reported 650 suspected cases, and at least 38 cases required liver Transplantation, 9 died. Existing evidence has not found a clear epidemiological association between cases, and it is not yet supported as an infectious disease. Unknown etiologyThe etiology and pathogenesis of severe acute hepatitis in children is still under study. The prevention and control measures proposed in the “Guide” mainly include, strengthen hand hygiene, pay attention to wearing masks and eating hygiene. In clinical work, medical staff need to take standard precautions and report suspected cases in a timely manner as required.
Guidelines for the diagnosis and treatment of severe acute hepatitis in children of unknown origin (Trial)
Severe acute hepatitis of unknown etiology was first reported in Scotland on 31 March 2022< span> (acute severe hepatitis of unknown aetiology in children, ASHep-UA), Since then, such cases have appeared in many countries or regions around the world, and the proportion of severe cases is high, which has attracted widespread attention. Since April 12, 2022, the official websites of the European Center for Disease Control and Prevention and the World Health Organization (WHO) have published information about the disease many times. On April 23, 2022, WHO issued diagnostic recommendations, but due to the unknown etiology, there is no recommendation for treatment. There are no related case reports in my country. In order to effectively strengthen the early identification and standardized diagnosis and treatment of the disease, and make every effort to improve the treatment effect, our committee has formulated the “Diagnosis and Treatment of Severe Acute Hepatitis in Children of Unknown Cause” based on relevant reports and literature and combined with the practice of hepatitis diagnosis and treatment. Guidelines (for Trial Implementation).
I. Popularity profile
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On March 31, 2022, in Scotland, England, 5 children with unexplained severe hepatitis were reported within 3 weeks. The children were 3 to 5 years old. On April 5, 2022, the United Kingdom reported to WHO an increase in cases of unexplained acute hepatitis in healthy children under 10 years of age. Most of the children had vomiting, jaundice, and elevated transaminases. As of May 20, 2022, data from the European surveillance system showed that the disease can be seen in children of all ages, and is more common in children under the age of 5; 14.1% of hospitalized children require intensive care units. On May 27, 2022, WHO announced that 33 countries reported 650 suspected cases, at least 38 required liver transplantation, and 9 died.
Existing evidence has not found a clear epidemiological association between the cases and does not yet support Infectious diseases.
The etiology and pathogenesis of severe acute hepatitis in children of unknown etiology is still unknownresearching. At present, WHO believes that although the hypothesis of adenovirus infection as the cause is reasonable, adenovirus usually causes mild, self-limited gastrointestinal or respiratory tract infections in young children, and cannot fully explain some of the more serious clinical manifestations of the disease. Therefore, the association between the disease and adenovirus needs to be further clarified. Most of the children have not been vaccinated against the new coronavirus, which does not support the hypothesis that the disease is related to the side effects of the new coronavirus vaccine. Other causative factors are still being explored, for example, during the epidemic of new coronary pneumonia, the low level of adenovirus prevalence increased the susceptibility of children; the emergence of new adenoviruses; adenovirus combined with new coronavirus infection; Complications of 2019-nCoV infection lead to the activation of immune cells mediated by superantigens, thereby causing multisystem inflammatory syndrome in children, etc. The exploration of other pathogens is also underway, and non-infectious factors need to be further ruled out.
Clinical performance
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Acute onset, mostly manifested as gastrointestinal symptoms such as fatigue and anorexia, nausea, vomiting, diarrhea, abdominal pain, etc.< /span>, followed byyellow-red urine, yellow-stained skin and sclera, some children may have white stool, enlarged liver, fever and respiratory symptoms, Individuals may have spleen enlargement. A small number of cases can progress to acute liver failure in a short period of time, appearing Progressive aggravation of jaundice, hepatic encephalopathy, etc.manifestations.
4. Case definition
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(1) Suspected cases: Since October 1, 2021, patients with Acute hepatitis (non-A, B, C, D, E hepatitis) and serum transaminase >500IU/L (ALT or AST), age 16 years and below.
(2) Epidemiologically associated cases: Patients with acute hepatitis (non-A, B, C, D, E) of any age who have been in close contact with a suspected case since October 1, 2021.
(3) There are currently no diagnostic criteria for confirmed cases.
Suspected and epidemiologically associated cases should be excluded from drugs, common non-hepatitis viral infections (eg EB virus, cytomegalovirus, etc.), autoimmune diseases, genetic metabolic diseases, etc.
V. Diagnosis of acute liver failure strong>
A suspected or epidemiologically linked case meets all three of the following criteria:
1. Acute-onset liver disease without evidence of chronic liver disease;
2. Biochemical evidence of severe liver injury;
3. Coagulation abnormalities that cannot be corrected by vitamin K, and meet one of the following twoOne: (1) Prothrombin time (PT) ≥ 15s or International Standard Ratio (INR) ≥ 1.5, with hepatic encephalopathy; (2) PT ≥ 20 s or INR ≥ 2, with or without hepatic encephalopathy.
6. Laboratory inspection
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The following laboratory tests are carried out according to the needs of the disease to assist in clarifying the cause and judging the disease.
(1) Routine inspection. Blood routine and reticulocyte, C-reactive protein, procalcitonin, urine, stool routine and other indicators.
(2) Blood biochemical examination.
1. Liver function: Alanine Acid aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin and direct bilirubin, albumin, alkaline phosphatase, γ-glutamyltransferase, bile acids, etc.
2. Others: blood electrolytes, blood glucose, lactate, blood ammonia, kidney function, myocardial enzymes, etc.
(3) Coagulation function test. PT, prothrombin activity, INR and activated partial thromboplastin time, etc.
(4) Pathological examination.
Except for Hepatitis A, B, C, D and E infection , as many samples as possible should be taken for etiological investigation, including blood (whole blood and plasma), respiratory (nasopharyngeal or oropharyngeal swabs, nasopharyngeal aspirate, etc.) ), stool and urine samples, etc. Tissue samples can be preserved if a puncture examination is required clinically. The following etiological examinations are recommended as a priority. During unconditional testing, specimens should be actively collected and properly stored for future testing.
1. Nucleic acid detection: Appropriate specimens are blood, respiratory tract or tissue samples. Those who have the conditions try to complete the new coronavirus, cytomegalovirus, Epstein-Barr virus, human herpes virus type 6, human enterovirus (common type of enterovirus), herpes simplex virus, adenovirus (pay attention to the type of adenovirus that can be detected by the reagent, Virus nucleic acid detection such as adenovirus 40/41) and parvovirus B19 should be included as much as possible; for those with gastrointestinal symptoms such as vomiting and diarrhea, human adenovirus, rotavirus and norovirus nucleic acid detection can be performed with stool specimens.
2. Antigen test: If you have gastrointestinal symptoms such as vomiting and diarrhea, you can Antigens such as adenovirus, rotavirus, and norovirus are detected in stool samples.
3. Serum-specific antibody detection: If conditions permit, try to complete the new coronavirus , Epstein-Barr virus, cytomegalovirus, parvovirus B19 and herpes simplex virus and other virus-specific IgM and IgG detection.
4. For those with negative etiological examinations and a high clinical suspicion of infection, macroscopic analysis of blood, liver puncture tissue and other samples can be performed. Genome next-generation sequencing.
(5) Other checks. According to the needs of clinical diagnosis and treatment, poison screening, drug testing, immune function testing, autoimmune antibody testing and genetic metabolic disease screening can be performed.
(6) Liver biopsy. According to the needs of diagnosis and treatment of the disease, determine whether to carry out liver biopsy. The biopsy tissue can be examined for pathology and etiology.
VII. Imaging performance
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(1) Abdominal ultrasound. Recommended preferred. Ultrasonography can be used to evaluate liver size, contour, stiffness, echogenicity of liver parenchyma, gallbladder biliary tract, and ascites, and it can also be used as a pre-transplant evaluation tool.
(B) MRI of abdomen. It can be selected according to the patient’s condition.
VIII. Treatment measures
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Comprehensive treatment measures, mainly symptomatic and supportive treatment, should be adopted, and changes in the condition should be closely observed, mental state should be assessed, laboratory indicators should be monitored, and complications should be prevented. Patients with liver failure should be promptly referred to hospitals with the ability to treat them.
(1) Hepatitis treatment.
1. General treatment and care:
(1) Rest: reduce physical exertion and avoid strenuous exercise; jaundice, vomiting, fatigue, anorexia appropriate bed rest.
(2) Nutritional support: ensure calorie intake, The child was given a high-carbohydrate, low-fat, high-quality protein diet, supplemented with multivitamins. Insufficient food requires intravenous supplementation.
(3) Monitor the changes of the condition, actively correct hypoalbuminemia, hypoglycemia, water-electrolyte and acid-base balance disorders, Be alert to complications such as liver failure.
2. Symptomatic treatment: Use liver-protecting drugs as appropriate, Those with cholestasis can use ursodeoxycholic acid, etc.; pay attention to keep the stool smooth, and those with constipation can use lactulose to reduce the absorption of toxins.
(2) Treatment of liver failure.
Can be transferred to an intensive care unit, where life support is given under close supervision. Close collaboration of multidisciplinary teams helps improve patient survival.
1. Fluid therapy: The total volume of intravenous fluids should be limited and the use of fluids containing Lactic acid fluid, adjust glucose infusion rate according to blood sugar level, maintain electrolyte balance, pay attention to correct hypoalbuminemia. If circulatory instability occurs, fluid resuscitation should be administered.
2. Hepatic encephalopathy and intracranial hypertension: Keep the environment quiet; reduce Unnecessary stimulation; use of sedative drugs with caution; timely detection and treatment of factors that may aggravate the condition, including infection, shock, gastrointestinal bleeding, acute kidney injury, and water and electrolyte disturbances; patients with cerebral edema and intracranial hypertension may be given Mannitol, hypertonic saline, and diuretics, among others.
3. Hyperammonemia: A significant increase in blood ammonia or accompanied by In hepatic encephalopathy, the protein intake should be reduced to 1 g/kg/d; oral or high enema such as lactulose should be given to promote defecation and reduce the absorption of ammonia in the intestine; intravenous infusion of arginine, aspartic acid-bird Amino acid, etc. to promote the excretion of ammonia; use branched-chain amino acids as appropriate. If it is still ineffective or the blood ammonia is seriously increased, blood purification treatment should be considered.
4. Coagulation disorders: intravenous vitamin K1 supplementation; active bleeding Or supplement fresh frozen plasma and/or platelets during invasive operations, and cryoprecipitate can be given for low fibrinogen (<1g/L); if there is no active bleeding or invasive operations, it is not recommended to routinely give blood products to correct coagulation abnormalities To avoid transfusion-related adverse reactions such as fluid overload.
5. Respiratory failure: If hypoxia occurs, use nasal cannula to inhale oxygen, For those who still do not relieve or aggravate, non-invasive or invasive ventilation should be given as appropriate.
6. Cardiovascular dysfunction: Maintain effective circulating blood volume; For those with decreased cardiac function, vasopressors and cardiotonic drugs can be given to maintain proper blood pressure and improve myocardial contractility.
7. Acute kidney injury: Reduce or stop diuretics and avoid them Nephrotoxic drugs to maintain effective blood volume. With hypotension, terlipressin or norepinephrine combined with albumin infusion can be used. Patients with severe oliguria or anuria, fluid overload, progressive increase in serum creatinine, severe electrolyte and acid-base balance disturbances after drug treatment can be treated with renal replacement therapy.
8. Control secondary infections: Should stay if secondary infections are suspected Antibacterial drug treatment was started after taking the relevant etiological specimens, and adjusted in time according to the results of culture and drug susceptibility after the pathogen was identified, and discontinued as soon as possible after infection control.
9. Extracorporeal liver support therapy: mainly used for patients who cannot be relieved by conventional treatment Serious coagulation abnormalities, hepatic encephalopathy, etc., or as a transition therapy before liver transplantation. Plasma exchange, hemoperfusion and plasma adsorption can be used as appropriate.
10. Liver transplantation: patients with severe liver failure who fail to respond to medical treatment, A multidisciplinary team evaluation should be organized as early as possible to decide whether to perform liver transplantation.
IX. Prevention and control measures
(1) Strengthen hand hygiene, pay attention to wearing masks and food hygiene, etc.
(2) During clinical work, medical staff need to take standard precautions, and once a suspected case is found, they should report it in time as required. strong>
click”read the original text span>“, enter the official website of the National Health Commission
p>Editor | Ma Yuan
Source | Healthy China Beijing Daily