China News Service, June 16. According to the website of the National Health and Health Commission, recently, the General Office of the National Health and Health Commission issued a guideline for the diagnosis and treatment of children with severe acute hepatitis of unknown cause (trial).
The General Office of the National Health and Health Commission pointed out that since March 2022, many countries and regions around the world have reported severe acute hepatitis of unknown aetiology in children (ASHep-UA), and the proportion of severe cases is high. Caused widespread concern.
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 and formulated the "Guidelines for Diagnosis and Treatment of Severe Acute Hepatitis in Children of Unknown Cause (Trial)".
details as follows:
Guidelines for the diagnosis and treatment of severe acute hepatitis in children of unknown etiology
(trial)
On March 31, 2022, severe acute hepatitis of unknown aetiology in children (ASHep-UA) was reported for the first time in Scotland, UK. Since then, such cases have occurred in many countries or regions around the world, and the proportion of severe cases is relatively high. high and 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, the 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 commission has formulated the "Guidelines for the Diagnosis and Treatment of Severe Acute Hepatitis in Children of Unknown Cause (Trial)" based on relevant reports and literature and combined with the practice of hepatitis diagnosis and treatment.
1. Popularity
On March 31, 2022, five children aged 3 to 5 years had developed unexplained severe hepatitis within 3 weeks in Scotland, UK.
On April 5, 2022, the United Kingdom reported to WHO that there has been an increase in cases of unexplained acute hepatitis in healthy children under the age of 10. Most of the children have 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.
The available evidence has not found a clear epidemiological association between the cases, and it is not yet supported as an infectious disease.
The etiology and pathogenesis
The etiology and pathogenesis of severe acute hepatitis in children of unknown etiology is still under investigation.
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 has increased the susceptibility of children; the emergence of new adenoviruses; adenovirus combined with new coronavirus infection; complications of new coronavirus infection lead to superantigen-mediated Immune cell activation, thereby causing multisystem inflammatory syndrome in children, etc.
Exploration of other pathogens is also underway, and non-infectious factors need to be further ruled out.
3. Clinical manifestations
Acute onset, mostly manifested as fatigue and anorexia, nausea, vomiting, diarrhea, abdominal pain and other gastrointestinal symptoms, followed by yellow-red urine, yellow-stained skin and sclera, and some children may have white stools and swollen liver Large, fever and respiratory symptoms, individual may have spleen enlargement.
A small number of cases can progress to acute liver failure in a short period of time, with progressive aggravation of jaundice and hepatic encephalopathy.
4. Case Definition
(1) Suspected cases: from October 1, 2021, with acute hepatitis (non-A, B, C, D, E hepatitis) and serum aminotransferase >500IU/L (ALT or AST), aged 16 years old and below.
(2) Epidemiologically related cases: From October 1, 2021, patients with acute hepatitis (non-A, B, C, D, and E hepatitis) of any age who have been in close contact with suspected cases.
(3) There are currently no diagnostic criteria for confirmed cases.
Suspected cases and epidemiologically related cases should be excluded from hepatitis caused by drugs, common non-hepatitis virus infections (such as Epstein-Barr virus, cytomegalovirus, etc.), autoimmune diseases, and genetic metabolic diseases.
The diagnosis of acute liver failure
Suspected cases or epidemiologically linked cases meet the following 3 criteria at the same time:
1. Acute onset of liver disease without evidence of chronic liver disease;
2. Biochemical evidence of severe liver damage;
3. Coagulation abnormalities that cannot be corrected by vitamin K, and meet one of the following two conditions: (1) Prothrombin time (PT) ≥ 15s or International Standard Ratio (INR) ≥ 1.5, with hepatic encephalopathy; (2) PT ≥ 20s or INR≥2, with or without hepatic encephalopathy.
6. Laboratory inspection
The following laboratory tests are required according to the condition to assist in clarifying the cause and judging the condition.
(1) Routine inspection.
Blood routine, reticulocyte, C-reactive protein, procalcitonin, urine, stool routine and other indicators.
(2) Blood biochemical examination.
1. Liver function: alanine aminotransferase (ALT), aspartate aminotransferase (AST), total and direct bilirubin, albumin, alkaline phosphatase, γ-glutamyl transfer enzymes, bile acids, etc.
2. Others: blood electrolytes, blood sugar, lactic acid, blood ammonia, renal function, myocardial enzymes, etc.
(3) Coagulation function test.
PT, prothrombin activity, INR and activated partial thromboplastin time, etc.
(4) Pathological examination.
In the case of excluding hepatitis A, B, C, D and E virus infection, as many samples as possible should be obtained for etiological investigation, including blood (whole blood and plasma), respiratory (nasopharyngeal or oropharyngeal swabs) sputum, nasopharyngeal aspirates, etc.), fecal 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: suitable 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 Viruses, adenoviruses (pay attention to the types of adenoviruses that can be detected by the reagent, and should try to include adenovirus 40/41), parvovirus B19 and other viral nucleic acids; for those with gastrointestinal symptoms such as vomiting and diarrhea, stool samples can be used for human adenovirus testing. Virus, rotavirus and norovirus nucleic acid detection.
2. Antigen detection: For those with gastrointestinal symptoms such as vomiting and diarrhea, antigen detection such as adenovirus, rotavirus, and norovirus can be performed in stool samples.
3. Serum-specific antibody detection: Those with conditions should try to complete the detection of virus-specific IgM and IgG such as new coronavirus, Epstein-Barr virus, cytomegalovirus, parvovirus B19 and herpes simplex virus.
4. For those with negative etiological examination and high clinical suspicion of infection, metagenome next-generation sequencing can be performed on samples such as blood and liver puncture tissue.
(5) Other inspections.
Toxic screening, drug testing, immune function testing, autoimmune antibody testing, and genetic metabolic disease screening can be performed according to the needs of clinical diagnosis and treatment.
(6) Liver biopsy.
Whether to carry out liver biopsy is determined according to the needs of diagnosis and treatment of the disease, and the biopsy tissue can be examined for pathology and etiology.
7. Imaging performance
(A) Abdominal ultrasound.
Recommended first choice.
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 situation of the patient.
Eight, treatment measures
Comprehensive treatment measures based on symptomatic and supportive treatment should be adopted, and changes in the condition should be closely observed, mental status 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) Treatment of hepatitis.
1. General treatment and care:
(1) Rest: reduce physical exertion and avoid strenuous exercise; when jaundice, vomiting, fatigue, and anorexia occur, appropriate bed rest should be taken.
(2) Nutritional support: ensure calorie intake, and give high-carbohydrate, low-fat, high-quality protein diets to children who can eat, and supplement multivitamins.
Insufficient food requires intravenous supplementation.
(3) Monitor the changes in the condition, actively correct hypoalbuminemia, hypoglycemia, water-electrolyte and acid-base balance disorders, and be alert to complications such as liver failure.
2. Symptomatic treatment: choose liver-protecting drugs as appropriate, and ursodeoxycholic acid can be used for those with cholestasis; 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.
They can be transferred to the intensive care unit and given life support under strict monitoring.
Close collaboration of multidisciplinary teams helps improve patient survival.
1. Fluid therapy: The total amount of intravenous infusion should be limited, the use of lactic acid-containing fluids should be avoided, the glucose infusion rate should be adjusted according to the blood glucose level, electrolyte balance should be maintained, and hypoalbuminemia should be corrected.
If circulatory instability occurs, fluid resuscitation should be administered.
2. Hepatic encephalopathy and intracranial hypertension: keep the environment quiet; reduce unnecessary stimulation; use sedatives with caution; promptly identify and treat factors that may aggravate the condition, including infection, shock, gastrointestinal bleeding, acute kidney injury, and water Electrolyte imbalance, etc.; for those with cerebral edema and intracranial hypertension, mannitol, hypertonic saline and diuretics can be given.
3. Hyperammonemia: When blood ammonia is significantly increased or accompanied by 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 amount of ammonia in the intestine. Absorption; intravenous infusion of arginine, aspartic acid-ornithine, 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; supplementation of fresh frozen plasma and/or platelets when there is active bleeding or invasive procedures, cryoprecipitate can be given if fibrinogen is reduced (<1g/L); if there is no active bleeding Or invasive procedures, it is not recommended to routinely administer blood products to correct coagulation abnormalities to avoid transfusion-related adverse reactions such as fluid overload.
5. Respiratory failure: if oxygen inhalation through nasal cannula occurs in the event of hypoxia, if it is still not relieved or aggravated, non-invasive or invasive ventilation should be given as appropriate.
6. Cardiovascular dysfunction: maintain effective circulating blood volume; those with reduced blood pressure and cardiac dysfunction can be given vasopressor and inotropic drugs to maintain proper blood pressure and improve myocardial contractility.
7. Acute kidney injury: reduce or stop diuretics, avoid the use of nephrotoxic drugs, and 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 of secondary infection: When secondary infection is suspected, antibiotic treatment should be started after collecting relevant etiological specimens. After the pathogen is identified, it should be adjusted in time according to the results of culture and drug susceptibility, and it should be discontinued as soon as possible after infection control.
9. Extracorporeal liver support therapy: It is mainly used for severe coagulation abnormalities and hepatic encephalopathy that cannot be relieved by conventional treatment, or as a transitional treatment before liver transplantation.
Plasma exchange, hemoperfusion and plasma adsorption can be used as appropriate.
10. Liver transplantation: For patients with severe liver failure who are ineffective in medical treatment, a multidisciplinary team should be organized for evaluation as soon as possible to decide whether to perform liver transplantation.
9. Prevention and control measures
(1) Strengthen hand hygiene, pay attention to wearing masks and food hygiene, etc.
(2) In clinical work, medical staff need to take standard precautions, and once a suspected case is found, they should report it in a timely manner as required.