Domestic experts appeal: for children of unknown cause of hepatitis should be prepared and technical reserves

WHO is closely following the development of unexplained severe hepatitis in unexplained children reported in many countries, and as of 2 May, WHO has received at least 228 cases of hepatitis in children that may be associated with unexplained viral infections, with more than 50 cases under investigation.

At present, WHO has reported at least 1 case of unexplained child hepatitis deaths, in addition, the Indonesian Ministry of Health reported that 3 children died from suspected acute hepatitis in Jakarta last month, and tests are currently being carried out to confirm the cause of their death.

Since the UK reported a sudden surge in acute hepatitis in children in the UK in early April, it has been of great concern to the global medical and health community, and much of the available evidence points to an adenovirus known as HAdV-41.

On May 4, an online expert seminar was held by the Virology Branch and Hepatology Branch of the Beijing Medical Association and Professor Wang Fusheng, an academician of the Chinese Academy of Sciences, to discuss acute severe hepatitis in children of unknown origin from the aspects of epidemiology, etiology, clinical diagnosis and treatment, and liver transplantation. China's top experts in the field have unanimously called for the establishment of a virus surveillance system, especially for the strengthening of research and technical reserves for common and past-neglected adenoviruses.

The "number one suspect" adenovirus allegations remain insufficient

Zhuang Hui, academician of the Chinese Academy of Engineering and epidemiologist, said: "The epidemiological and clinical data reported globally on unexplained hepatitis in children are not complete enough, and there is a lack of information on immunological testing, the definition criteria for confirmed and suspected cases are also relatively coarse, and it is not clear which cofactors make the disease worse after childhood infection, and these aspects need to be judged through the further improvement of relevant data in the future." ”

Professor Chen Chengwei, a well-known expert in liver disease, put forward several aspects that should be paid attention to at present. He said: "The first is the pathogenesis, to find out whether there is a causal relationship between the onset of childhood disease and adenovirus 41 infection; secondly, from the clinician's point of view, it is more important to focus on the treatment problem, that is, once such a case occurs, what should be done?" Whether to use inhibitors, such as large doses of hormones, is required for treatment; on the other hand, it is necessary to prepare for liver transplantation in children and whether the artificial liver can play a role. ”

The data shows that among these reported child cases, about 20 children need liver transplantation, accounting for nearly 10%. Professor Xia Qiang, president of Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine and an expert in liver surgery, talked about the accessibility and safety of children's liver transplantation at present, he said: "China's children's liver transplant surgery has developed very rapidly in the past decade, and now China's annual children's liver transplantation has reached about 1,000 cases, more than 600 cases in the United States, and the 5-year survival rate can exceed 90%. ”

Currently, both the UK and the US are initially targeting unexplained hepatitis in children as adenovirus infection. In this regard, Professor Xie Zhengde, director of the Infection and Virus Research Office of Beijing Children's Hospital affiliated to Capital Medical University and Beijing Pediatric Research Institute, said: "Adenovirus type 40 and 41 usually cause diarrhea in the past, although there are other viruses co-infected with liver damage, but it is very rare, mainly in patients with suppressed immune function. ”

Xie Zhengde said that a variety of non-hepatitis virus infections may also cause liver damage or hepatitis complications, and even liver failure, in addition to adenovirus, rotavirus, measles virus, hantavirus and other infections also need further study.

"Enhanced multidisciplinary collaboration and pathogenic surveillance will help us answer these questions." Xie Zhengde said. He also stressed that a distinction should be made between children with co-liver damage and which had liver damage in the first place, and that it was more worthwhile to study such patients who were not co-liver damage.

Although adenovirus has so far been considered the "number one suspect" who can cause acute severe hepatitis in children, scientists still have a hard time explaining why this common respiratory virus can cause severe illness in children. Some researchers suspect that adenoviruses may have genetic mutations or recombination.

Zhu Zhen, a researcher at the Institute of Viral Disease Prevention and Control of the Chinese Center for Disease Control and Prevention, explained the etiology of adenovirus. She said: "After homologous recombination of adenovirus genes, it can change the penitency of tissues, resulting in changes in the disease spectrum. At present, there is no systematic monitoring of adenoviruses on the mainland. ”

In this regard, Professor Chen Jinjun, deputy director of the Department of Infectious Medicine of Nanfang Hospital of Southern Medical University, suggested that non-hepatophilic virus blood samples from children and adults can be taken out for a retrospective investigation, and for acute liver injury, if there is a tissue sample, prospective research can also be carried out.

At present, there is no evidence that acute hepatitis in children is related to the new crown virus. Zhang Qiwei, a professor at the Institute of Pathogenic Microbiology of Jinan University and the Guangdong Provincial Key Laboratory of Virology, believes that indirectly related factors of the new crown cannot be ruled out, such as the onset of infection with adenovirus after infection with the new crown.

Strengthen monitoring networks and technical reserves

Cases of unexplained hepatitis in children have not yet been monitored on the mainland, but several experts have called for the corresponding epidemiological plans to be activated in advance, the establishment of a monitoring network for relevant etiology and metagenomics, and the change of children's immune systems in the post-epidemic era.

Professor Lu Fengmin, professor of the Department of PathogenIc Biology of Peking University School of Basic Medical Sciences and director of the Center for Infectious Diseases of Peking University, said: "The exposure of different pathogens is actually a kind of training for children's immunity, and after the epidemic, what kind of changes in children's immune systems are worth studying, and we can further understand whether the incidence of childhood infection is natural immunity or adaptive immunity." ”

Professor Dang Shuangsuo, head of the new crown pneumonia medical treatment expert group and director of the Department of Infection of the Second Affiliated Hospital of Xi'an Jiaotong University, said: "First, we must further track related child cases, but the more important issue is that the process of childhood onset is actually the process of immune response, and this response process to the onset of children's diseases often has a lagging effect, which should be observed and studied for a long time. ”

Experts believe that although the number of cases of unexplained acute hepatitis in children that have attracted the attention of WHO has exceeded 200 cases, a significant increase over previous years, at present, these cases are still mainly sporadic and do not show the characteristics of cluster infection, which may indicate that the virus is less contagious.

Niu Junqi, professor of the Infection Disease Center of the First Hospital of Jilin University and an expert in hepatobiliary and pancreatic medicine, said: "If the virus is indeed relatively weak, then there will not be many people who will fall ill after infection, and from this characteristic point of view, it will not cause a large-scale and wider epidemic." ”

He also said that to determine whether the "real culprit" is an adenovirus, it can be cultured by pathogen replication and verified in animal experiments whether it can lead to the onset of the disease.

Professor Ning Qin of the Institute of Infectious Diseases of Tongji Hospital affiliated to Huazhong University of Science and Technology said: "On the one hand, the CDC should organize epidemiological investigations and start the plan; on the other hand, for adenoviruses reported abroad, we should also make preliminary reserves in terms of detection technology, standardize the knowledge system, and improve the success rate of treatment." ”

Professor Zhou Dongming, an infectious disease expert at Tianjin Medical University, believes that while strengthening pathogen research, it is also very important to develop adenovirus vaccines. Zhou Dongming told the first financial reporter that his team at Tianjin Medical University has been working on vaccine research and development against adenovirus type 41.

"There have been studies of adenovirus vaccines in China, but they have not yet been pushed to the clinic, so there is no adenovirus vaccine for children to be vaccinated." Zhou Dongming told the first financial reporter, "For special groups, such as recruits and children, these high-incidence groups, adenovirus vaccination is still very necessary." ”