Acute Hepatitis Of Unknown Etiology Research Articles

The First Report of Coxiella burnetii as a Potential Neglected Pathogen of Acute Hepatitis of Unknown Causes in Egypt.

The World Health Organization (WHO) recently alerted the emergence of new pathogens causing acute hepatitis in children across several countries. This new situation directs us to the screening of neglected pathogens that cause acute hepatitis. Q-fever is a zoonotic disease, caused by Coxiella burnetii. Although a high seroprevalence of Coxiella burnetii was recorded in animals present in Egypt, Q-fever is still a neglected disease, and the diagnosis of Q-fever is not routinely performed in Egyptian hospitals. In this study, we performed a retrospective assessment for Coxiella burnetii in cases of hepatitis of unknown causes (HUC) enrolled in Assiut University hospitals, in Egypt. Out of 64 samples of HUC, 54 samples were negative for all hepatitis markers, labeled as acute hepatitis of unknown etiology (AHUE), and 10 samples tested positive for adenovirus and Hepatitis E virus (HEV). Q-fever was detected in 3 out of 54 (5.6%) of AHUE, and one sample was confirmed as coinfection of HEV/Q-fever. Jaundice was the most common clinical symptom developed in the patients. In conclusion, Coxiella burnetii was found to be a potential cause of acute hepatitis in HUC. The diagnosis of Q-fever should be considered in acute hepatitis cases in Egyptian hospitals.

Detection of human adenovirus F41 in wastewater and its relationship to clinical cases of acute hepatitis of unknown aetiology

As of 8 July 2022, the World Health Organization (WHO) have reported 1010 probable cases of acute hepatitis of unknown aetiology in children worldwide, including approximately 250 cases in the United Kingdom (UK). Clinical presentations have often been severe, with liver transplantation a frequent clinical outcome. Human adenovirus F41 (HAdV-F41) has been detected in most children with acute hepatitis, but its role in the pathogenesis of this infection has yet to be established. Wastewater-based epidemiology (WBE) has become a well-established tool for monitoring the community spread of SARS-CoV-2, as well as other pathogens and chemicals. In this study, we adopted a WBE approach to monitoring levels of HAdV-F40/41 in wastewater before and during an acute hepatitis outbreak in Northern Ireland. We report increasing detection of HAdV-F40/41 in wastewater, concomitant with increasing numbers of clinical cases. Amplicon whole genome sequencing further classified the wastewater-derived HAdV as belonging to the F41 genotype which in turn was homologous to clinically derived sequences. We propose that WBE has the potential to inform community surveillance of HAdV-F41 and can further contribute to the ongoing global discussion supporting HAdV-F41 involvement in acute hepatitis cases.

An Epidemic of Acute Hepatitis of Unknown Etiology in Children

An Epidemic of Acute Hepatitis of Unknown Etiology in Children

Severe Acute Hepatitis of Unknown Etiology in Indonesia: What Has Been Learned?

The world has witnessed increased incidences of severe acute hepatitis in children since early 2021, in which the total number of global cases was over 1,000 in July 2022. Those cases of severe acute hepatitis were intriguing, as they were not caused by the common hepatitis A-E viruses. Additionally, the cause remains unknown to date, thus named as severe acute hepatitis of unknown etiology. The World Health Organization, supported by regional and national health agencies, has issued the working case definitions in order to closely monitor the development of this disease worldwide. As one of its member states, Indonesia has also adopted the case definitions and subsequently issued a health decree to increase public awareness and to conduct an early surveillance on this illness. It remains to be seen whether this updated public health policy would be successful to control the numbers of cases of severe acute hepatitis of unknown etiology in Indonesia.

Acute Hepatitis of Unknown Etiology Among Young Children: Research Agenda by the ESPGHAN Hepatology Committee.

In April 2022, an increased incidence of acute hepatitis cases of unknown etiology among previously healthy children across the United Kingdom was described. Since, more than 270 cases from the United Kingdom and hundreds more from all across the world have been reported. The majority of affected children were younger than 6 years of age. The clinical presentation was nonspecific with diarrhea and vomiting usually preceding the appearance of jaundice, abdominal pain, nausea, and malaise. Approximately 5% have required liver transplantation. An infectious etiology has been considered likely given the epidemiological and clinical features of the reported cases. Between 50 and 60% of the children tested were diagnosed with adenovirus infection although a clear etiological connection has still to be demonstrated. No link with SARS-CoV-2 infection and COVID-19 vaccine was found. What is not clear to date is whether the high number of acute hepatitis cases reported is related to a true increase in incidence or heightened awareness following on from the initial reports from the United Kingdom. The Hepatology Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) developed a paper on the current outbreak of acute hepatitis of unknown etiology recognizing its importance and the need of approaching the current situation with a scientifically rigorous approach. The aims of the article are to summarize the current knowledge and to identify the most pertinent issues regarding the diagnosis and management of this condition and the research questions raised.

Acute hepatitis of unknown etiology: a proposed diagnostic approach.

Acute hepatitis of unknown etiology: a proposed diagnostic approach.

Attention should be paid to acute hepatitis of unknown etiology in children.

Since April 5, 2022, an increase in cases of severe acute hepatitis of unknown etiology among children with no underlying conditions was first reported in the United Kingdom (UK). Testing excluded viral hepatitis types A, B, C, D, and E and other known common and uncommon infectious and non-infectious causes of acute hepatitis. As of May 26, 2022, 650 cases of acute hepatitis of unknown etiology in children have been reported in at least 33 countries worldwide, with 99 additional cases pending classification. Here, the current prevalence of this condition around the world, a hazard analysis, possible causes, the risk of an outbreak in China, and advice on prevention have been briefly reviewed.

The event of acute hepatitis of unknown etiology in children

Recently, the cases of acute hepatitis of unknown etiology (AHUE) in children worldwide have been increasing continuously and rapidly, involving more than 396 cases in 26 countries, and global public health actions, including surveillance, health alerts, research, are being implemented. AHUE mainly affects immunocompetent children with typical acute hepatitis, which can be severe and require liver transplantation. There are few systematic studies at present; the risk factors are unknown, the etiology remains to be established, and the clinical features and pathogenesis remain elucidated. It is urgent to strengthen the monitoring and research of AHUE cases.

Hepatitis of unknown etiology in children: What we know and what we can do?

Recently, acute hepatitis of unknown etiology in children has gained great concern since March 2022. The disease was first reported by Public Health Scotland. Cases increased rapidly and are now reported in 33 countries worldwide. All cases are predominantly aged under 5 years old. Most patients presented with jaundice, and remarkably, some cases progress to acute liver failure. Until now, the etiology is not fully elucidated, and the investigations are ongoing. Adenovirus infection seems to be an important factor. Several hypotheses on the etiology have been proposed. This review aims to summarize current research progress and put forward some suggestions.

Hepatitis of unknown aetiology in children - epidemiological overview of cases reported in Europe, 1 January to 16 June 2022.

Following the report of an excess in paediatric cases of severe acute hepatitis of unknown aetiology by the United Kingdom (UK) on 5 April 2022, 427 cases were reported from 20 countries in the World Health Organization European Region to the European Surveillance System TESSy from 1 January 2022 to 16 June 2022. Here, we analysed demographic, epidemiological, clinical and microbiological data available in TESSy. Of the reported cases, 77.3% were 5 years or younger and 53.5% had a positive test for adenovirus, 10.4% had a positive RT-PCR for SARS-CoV-2 and 10.3% were coinfected with both pathogens. Cases with adenovirus infections were significantly more likely to be admitted to intensive care or high-dependency units (OR = 2.11; 95% CI: 1.18–3.74) and transplanted (OR = 3.36; 95% CI: 1.19–9.55) than cases with a negative test result for adenovirus, but this was no longer observed when looking at this association separately between the UK and other countries. Aetiological studies are needed to ascertain if adenovirus plays a role in this possible emergence of hepatitis cases in children and, if confirmed, the mechanisms that could be involved.

Non-hepatotropic viral hepatitis and its causative pathogens: The ongoing need for monitoring in children with severe acute hepatitis of unknown etiology.

Non-hepatotropic viral hepatitis and its causative pathogens: The ongoing need for monitoring in children with severe acute hepatitis of unknown etiology.

Severe Acute Hepatitis of Unknown Origin in Children: What Do We Know Today?

In May 2022, the UK International Health Regulations National Focal Point notified World Health Organization of 176 cases of severe acute hepatitis of unknown etiology in children under 10 years of age. From that moment on, cases of severe acute hepatitis of unknown origin in children began to be reported in several countries. As of June 17, 2022, a total of 991 cases had been reported in 35 countries worldwide, 50 children needed a liver transplant and 28 patients died. According to information published by ECDC, 449 cases have been detected in 21 EU countries. The children were between 1 month and 16 years of age. Adenovirus was detected in 62.2% of the analyzed samples. So far, the cause of these cases is unknown and many hypotheses remain open, but hepatitis A–E viruses and COVID-19 vaccines have been ruled out. A possible hypothesis has been published to explain the cause of these cases of severe hepatitis, according to which it could be a consequence of adenovirus infection in the intestine in healthy children previously infected with SARS-CoV-2. No other clear epidemiological risk factors have been identified to date. Thus, at this time, the etiology of the current cases of hepatitis remains under active investigation.

A case of severe acute hepatitis of unknown etiology requiring liver transplantation in a child with adenovirus infection

The article presents a clinical observation of severe acute hepatitis of unknown aetiology with liver transplantation in a 16-year-old child, which occurred in October 2021. Initial symptoms were abdominal pain, diarrhea. The general wellbeing of the girl did not suffer, there was no fever, no intoxication syndrome. Over the next days, she began to notice the appearance of edema on the legs, an increase in the size of the abdomen. From the 10-11th day of illness – darkening of urine, acholia of feces, jaundice were observed. She was examined by a pediatrician, a biochemical blood test was performed, according to the results the girl was hospitalized with a diagnosis of acute hepatitis. According to the severity of the condition, she was hospitalized in the ICU. On admission she complained of abdominal pain, jaundice, edema, and weakness. On examination: jaundice, scleral icterus, hemorrhagic rash at the site of the tourniquet, bleeding from injection sites, hepatomegaly, anasarca. In blood tests: progressive anemia, thrombocytopenia, increased AST (with a decrease in dynamics against the background of progression of liver failure), a decrease in total protein and albumin, fibrinogen, prothrombin according to Quick. Laboratory excluded viral hepatitis A-E. The only infectious agent diagnosed was group F adenovirus in feces. By the third day of hospitalization developed of multiple organ failure, DIC. On the 4th day of hospitalization, the child was transferred to a specialized hospital, where an emergency liver transplantation was performed. The operation was successful, the child was discharged in a stable condition.

Гострий гепатит невизначеної етіології: завдання епідеміологічного нагляду в Україні в сучасних умовах

The purpose of the study was to analyze cases of acute hepatitis of undetermined etiology and define the main problems and tasks of epidemiological surveillance in Ukraine for emergent disease of acute hepatitis of unknown etiology. Materials and methods. The method of retrospective epidemiological analysis of data from open sourses on cases of acute hepatitis of undetermined etiology and the bibliosemantic method were used. Results and discussion. It was found that from April 5 to May 27, 2022, 650 cases of acute hepatitis of undetermined etiology in children were registered in 33 countries in 5 World Health Organization regions. The majority of reported cases, 58%, are in the World Health Organization European Region (22 countries). According to data as of May 31, 2022, we realized that the highest incidence of acute hepatitis of unknown etiology among children under 16 years old was observed in countries such as Great Britain – 50.8%, Spain – 11%, Italy – 9.5%, Portugal – 4.9%, the Netherlands and Belgium – 4.6% each, Austria and Cyprus – 0.7% each, Denmark – 2.3%, Greece and Norway – 1.6% each, and Ireland – 2.6%. Out of 305 patients with acute hepatitis of unknown etiology, 237 people were hospitalized, which is 77.7% of cases. Most of them were hospitalized in the UK – 65% of patients, Italy – 11% of cases, Spain – 8.0% of patients. In total, 7.5% of patients were in intensive care units, the largest number was in the UK – 60.9% of cases, Ireland and Spain – 13% of patients. In the age and sex structure of the diseased, children aged 5 years and younger (76%) and female persons prevailed. The etiology is unknown, but there is an association of cases with adenovirus type 41. Samples of whole blood, serum, urine, feces, airway washes, and, if possible, liver biopsies were examined in sick children under 16 years old. A total of 199 cases of acute hepatitis of unknown etiology were tested for adenovirus, of which 59.3% were positive. PCR testing for SARS-CoV-2 was performed in 204 patients, and 11.8% of patients had positive results. Serological tests for SARS-CoV-2 samples of 34 patients were positive, 67.6% of samples. Vaccination against COVID-19 was reported in 72 patients with acute hepatitis of unknown etiology, of which 61 patients (85%) were not vaccinated. Conclusion. It is indicated that it is necessary to identify possible cases of acute hepatitis of undetermined etiology, implement epidemiological investigation of each case, inform medical workers and exchange information with specialists, practice educational work among the population

Severe Acute Hepatitis of Unknown Etiology in Children: Is It Caused by Pathogens or Non-infectious Factors?

Recently, an outbreak of severe acute hepatitis of unknown etiology in children has been reported in more than 27 countries worldwide. However, information on its prevalence in different countries and regions is still lacking. The evidence is suggestive of a potential viral infection, but this has not been fully confirmed. Cases of this disease have been reported in children, mainly in those younger than 5 years old. The reason for the age range of the disease requires further investigation.

Interim Analysis of Acute Hepatitis of Unknown Etiology in Children Aged

On April 21, 2022, CDC issued a health advisory† encouraging U.S. clinicians to report all patients aged <10 years with hepatitis of unknown etiology to public health authorities, after identification of similar cases in both the United States (1) and Europe.§ A high proportion of initially reported patients had adenovirus detected in whole blood specimens, thus the health advisory encouraged clinicians to consider requesting adenovirus testing, preferentially on whole blood specimens. For patients meeting the criteria in the health advisory (patients under investigation [PUIs]), jurisdictional public health authorities abstracted medical charts and interviewed patient caregivers. As of June 15, 2022, a total of 296 PUIs with hepatitis onset on or after October 1, 2021, were reported from 42 U.S. jurisdictions. The median age of PUIs was 2 years, 2 months. Most PUIs were hospitalized (89.9%); 18 (6.1%) required a liver transplant, and 11 (3.7%) died. Adenovirus was detected in a respiratory, blood, or stool specimen of 100 (44.6%) of 224 patients.¶ Current or past infection with SARS-CoV-2 (the virus that causes COVID-19) was reported in 10 of 98 (10.2%) and 32 of 123 (26.0%) patients, respectively. No common exposures (e.g., travel, food, or toxicants) were identified. This nationwide investigation is ongoing. Further clinical data are needed to understand the cause of hepatitis in these patients and to assess the potential association with adenovirus.

Indeterminate pediatric acute liver failure: Clinical characteristics of a temporal cluster of five children in the Netherlands in the spring of 2022.

There is increasing global concern of severe acute hepatitis of unknown etiology in young children. In early 2022, our center for liver transplantation in the Netherlands treated five children who presented in short succession with indeterminate acute liver failure. Four children underwent liver transplantation, one spontaneously recovered. Here we delineate the clinical course and comprehensive diagnostic workup of these patients. Three of five patients showed a gradual decline of liver synthetic function and had mild neurological symptoms. Their clinical and histological findings were consistent with hepatitis. These three patients all had a past SARS‐CoV‐2 infection and two of them were positive for adenovirus DNA. The other two patients presented with advanced liver failure and encephalopathy and underwent dialysis as a bridge to transplantation. One of these children spontaneously recovered. We discuss this cluster of patients in the context of the currently elevated incidence of severe acute hepatitis in children.

Pay close attention to the current characteristics and development trend of severe acute hepatitis with unknown etiology in children worldwide

In the past, acute hepatitis of unknown etiology in children was sporadic. However, during the last three weeks, there has been a trend of short-term outbreak around the world. As of May 3, 2022, at least 228 cases had been reported in about 20 countries and regions. The main clinical manifestations of the children included abdominal pain, diarrhea, vomiting, jaundice, and hepatomegaly. The liver functions including alanine aminotransferase and total bilirubin increased sharply. About 8.8% of the children needed liver transplantation. The etiology is not clear, but adenovirus type 41 is currently considered to be the most likely cause. Clinicians should keep alert to acute hepatitis of unknown etiology in children, strengthen epidemic surveillance, clinical treatment, and carry out necessary health education.

Trends in Acute Hepatitis of Unspecified Etiology and Adenovirus Stool Testing Results in Children - United States, 2017-2022.

In November 2021, CDC was notified of a cluster of previously healthy children with hepatitis of unknown etiology evaluated at a single U.S. hospital (1). On April 21, 2022, following an investigation of this cluster and reports of similar cases in Europe (2,3), a health advisory* was issued requesting U.S. providers to report pediatric cases† of hepatitis of unknown etiology to public health authorities. In the United States and Europe, many of these patients have also received positive adenovirus test results (1,3). Typed specimens have indicated adenovirus type 41, which typically causes gastroenteritis (1,3). Although adenovirus hepatitis has been reported in immunocompromised persons, adenovirus is not a recognized cause of hepatitis in healthy children (4). Because neither acute hepatitis of unknown etiology nor adenovirus type 41 is reportable in the United States, it is unclear whether either has recently increased above historical levels. Data from four sources were analyzed to assess trends in hepatitis-associated emergency department (ED) visits and hospitalizations, liver transplants, and adenovirus stool testing results among children in the United States. Because of potential changes in health care-seeking behavior during 2020-2021, data from October 2021-March 2022 were compared with a pre-COVID-19 pandemic baseline. These data do not suggest an increase in pediatric hepatitis or adenovirus types 40/41 above baseline levels. Pediatric hepatitis is rare, and the relatively low weekly and monthly counts of associated outcomes limit the ability to interpret small changes in incidence. Ongoing assessment of trends, in addition to enhanced epidemiologic investigations, will help contextualize reported cases of acute hepatitis of unknown etiology in U.S. children.

The relationship between adenovirus infection and severe acute hepatitis of unknown etiology

Adenovirus infection can occur in all regions or countries of the world, with no obvious seasonality, but pandemics mostly occur in winter or early spring. Adenovirus infection is self-limited among immunocompetent host with supportive care, however fatal infection can occur among immunocompromised patients, mainly affecting respiratory, gastrointestinal tract and adjunctiva and very rarely causing hepatitis, cholecystitis, pancreatitis, hemorrhagic cystitis, myocarditis, meningitis or encephalitis. Adenovirus hepatitis mainly occur in malignant tumors or organ transplantation patients, but acute severe hepatitis can occur even in immunocompetent children or adults. On 5 April 2022, WHO was notified of 10 cases of severe acute hepatitis of unknown etiology in children. As of 21 April 2022, at least 169 cases of acute hepatitis of unknown origin have been reported from 12 countries (including 11 WHO European Region countries and the United States). Adenovirus has been detected in at least 74 cases; SARS-CoV-2 was identified in 20 cases of those that were tested. Furthermore, 19 were detected with a SARS-CoV-2 and adenovirus co-infection. At present, the etiology has not been fully elucidated. The leading hypotheses center around adenovirus, and the relationship with SARS-CoV-2 needs to be further ruled out.