Acute Hepatitis Of Unknown Etiology Research Articles

Deaths Associated with Pediatric Hepatitis of Unknown Etiology, United States, October 2021-June 2023.

During October 2021-June 2023, a total of 392 cases of acute hepatitis of unknown etiology in children in the United States were reported to Centers for Disease Control and Prevention as part of national surveillance. We describe demographic and clinical characteristics, including potential involvement of adenovirus in development of acute hepatitis, of 8 fatally ill children who met reporting criteria. The children had diverse courses of illness. Two children were immunocompromised when initially brought for care. Four children tested positive for adenovirus in multiple specimen types, including 2 for whom typing was completed. One adenovirus-positive child had no known underlying conditions, supporting a potential relationship between adenovirus and acute hepatitis in previously healthy children. Our findings emphasize the importance of continued investigation to determine the mechanism of liver injury and appropriate treatment. Testing for adenovirus in similar cases could elucidate the role of the virus.

Severe Acute Hepatitis of Unknown Etiology in Pediatric Patients: Multidisciplinary Clinical Approach

Introduction: In mid-2022, the World Health Organization (WHO) declared a moderate-risk outbreak due to an increase in severe acute hepatitis cases of unknown etiology in children. Several reports suggested a viral infection link, with the outbreak spanning over 35 countries. By June 2022, Mexico reported 69 probable cases across 5 entities to the WHO. Case Presentation: A 4-year-old boy presented with vomiting, jaundice, choluria, and hepatomegaly. A multidisciplinary approach was employed, using an algorithm developed exclusively for clinical, epidemiological, and biochemical follow-up. Despite the negative identification of any associated microorganism and the absence of antibodies, liver function tests remained elevated. A fine needle liver biopsy was performed for diagnostic support, followed by histopathological study and sequencing and analysis of the complete high-depth transcriptome. Transcriptome analysis identified dysbiosis-related intestinal microbiota, including increased enterogenic and opportunistic pathogenic bacteria of the genus Clostridium, as well as HERV-K113, implicated in autoimmune disease development. Conclusions: The study's findings suggest possible immune-mediated mechanisms involving dysbiosis of the gut microbiota and the potential role of HERV-K113. Management and control of acute liver disease depend on specific causes, with the main challenge being early determination and implementation of optimal management strategies. The exact pathological mechanisms underlying pediatric acute hepatitis of unknown etiology remain elusive, warranting further studies to confirm or refute these hypotheses and elucidate the underlying pathological mechanisms

Histopathological findings from the investigation of paediatric acute hepatitis of unknown aetiology, United Kingdom 2022.

In 2022, there were global reports of increased numbers of acute hepatitis not explained by hepatitis A-E virus infection in children. This manuscript summarises histopathology results from 20 patients in the United Kingdom who underwent liver transplantor had a liver biopsy as part of aetiological investigations. All available histopathological samples were reviewed centrally as part of the outbreak investigation. A working group comprised of infection specialists, hepatologists and histopathologists met virtually to review the cases, presentation, investigations and histopathology. All 20 liver samples had evidence of inflammation without significant interface activity, and submassive confluent pan-lobular or multilobular hepatocellular necrosis. Overall, the predominant histopathological findings were of acute nonspecific hepatitis with submassive hepatic necrosis and central vein perivenulitis and endothelitis. Histopathological findings were a poor indicator of aetiology.

Hepatitis Aguda Grave de Origen Desconocido en Población Pediátrica Durante la Pandemia de Covid 19

This research aims to conduct an updated bibliographic review focused on the comparison of clinical cases in pediatric patients who presented with severe acute hepatitis of unknown etiology in order to evaluate the severity that may occur in this risk group, characterized by gastrointestinal symptoms, elevated liver enzyme values (greater than 500 IU/L), monitoring of liver function should be considered (5). For this study, scientific literature was consulted between January 2021 and June 2022 using platforms such as PubMed, Scopus, Elsiever, The Lancet, Web of Science, Medline. The total population analyzed consists of 18 pediatric patients who tested negative for hepatitis virus (A-E). Of which 4 patients are negative for SARS VOC 2, while the rest are confirmed positive cases, surprisingly 5 patients tested positive for adenovirus. Of the five hypotheses raised in this study, the one that had the greatest impact was that of adenovirus, which caused greater vulnerability, resulting from the reduced circulation of this virus in the last two years. It is still necessary to collect data on this disease, it is important to notify them in order to know their etiopathogenesis and subsequent therapeutic management.

Macrophage activation syndrome with acute hepatitis in a patient with adult-onset immunodeficiency with anti-interferon gamma antibodies: a case report

BackgroundMacrophage activation syndrome is a rare disorder leading to unregulated immune activity manifesting with nonspecific constitutional symptoms, laboratory abnormalities, and multiorgan involvement. We report the case of a patient who presented with acute hepatitis secondary to macrophage activation syndrome diagnosed by liver biopsy and successfully treated with intravenous immune globulin, anakinra, and rituximab.Case presentationA 42-year-old Laotian woman with adult-onset immunodeficiency with anti-interferon gamma antibodies presented with a fever, headache, generalized myalgia, dark urine, and reduced appetite in the setting of family members at home with similar symptoms. Her laboratory workup was notable for evidence of acute hepatitis without acute liver failure. After an unrevealing comprehensive infectious and noninvasive rheumatologic workup was completed, a liver biopsy was performed ultimately revealing the diagnosis of macrophage activation syndrome. She was successfully treated with intravenous immune globulin, anakinra, and rituximab.ConclusionThis case highlights the importance of maintaining macrophage activation syndrome on the differential of a patient with acute hepatitis of unknown etiology in the correct clinical context and the value of a liver biopsy in making a diagnosis when noninvasive testing is unrevealing.

Acute hepatitis of unknown etiology in children: Comparison between the U.K., U.S., and Japan, and ingenious clinical practice attempts

Acute hepatitis of unknown etiology in children: Comparison between the U.K., U.S., and Japan, and ingenious clinical practice attempts

A Report on a Nationwide Surveillance System for Pediatric Acute Hepatitis of Unknown Etiology in Korea.

Several cases of pediatric acute hepatitis of unknown etiology related to adenoviral infections have been reported in Europe since January 2022. The aim of this study was to compare the incidence, severity, possible etiology, and prognosis of the disease with those in the past in Korea. The surveillance group collected data between May and November 2022 using a surveillance system. Acute hepatitis of unknown etiology was defined in patients aged < 16 years with a serum transaminase level > 500 IU/L, not due to hepatitis A-E or other underlying causes. For comparison, data from 18 university hospitals were retrospectively collected as a control group between January 2021 and April 2022. We enrolled 270 patients (mean age, 5 years). The most common symptom was fever. However, the incidence was similar between 2021 and 2022. Liver function test results, number of patients with acute liver failure (ALF), liver transplantation (LT), death, and adenovirus detection rates did not differ between the two groups. None of the adenovirus-positive patients in either group experienced ALF, LT, or death. In the surveillance group, adenovirus-associated virus-2 was detected in four patients, one of whom underwent LT. Patients with an unknown etiology showed significantly higher bilirubin levels, a lower platelet count, and a higher LT rate than patients with a possible etiology. The incidence of pediatric acute hepatitis of unknown etiology and adenovirus detection rate have not increased in Korea.

Demystifying the global outbreak of severe acute hepatitis of unknown aetiology in children: A systematic review and meta-analysis

The sudden outbreak of severe acute hepatitis of unknown aetiology (SAHUA) in the first half of 2022 affected more than 1010 children in 35 countries worldwide. Dire clinical outcomes, such as acute liver failure necessitating transplantation, neurological symptoms, long-term sequelae, and death, highlight the need to determine the pathogenesis of this condition. Hypotheses on the aetiology include adenovirus and SARS-CoV-2 infections and an aberrant immune response to multiple pathogen exposure following lifting of lockdown measures but further investigation is required to reach an informed consensus. A literature search was performed on MEDLINE and EMBASE in accordance with PRISMA guidelines for systematic reviews. Primary studies reporting data on severe acute hepatitis of unknown aetiology in children from the COVID-19 era were selected for inclusion in our review. Data on patient demographics, clinical presentation and outcomes, and diagnostic testing for coinfection were extracted. Meta-analysis used a random-effects model. The 33 included studies (30 case series and 3 case-control studies) described a total of 3636 cases of SAHUA (reported 1 January, 2019-31 December, 2022), with a median age of 3.5years. Of these, 214 children (5.9%) received a liver transplant and 66 (1.8%) died. Whilst data on diagnostic testing was incomplete, the most frequently detected coinfections were with adenovirus and/or adeno-associated virus 2 (AAV2). Other common childhood respiratory and enteric pathogens, such as enterovirus, rhinovirus, and herpesviruses (EBV and HHV-6), were also identified. Coinfection with AAV2 and other common childhood pathogens may predispose children to develop this novel severe hepatitis. Altered susceptibility and response to such pathogens may be a consequence of immunological naivety following pandemic restrictions. Further investigations are needed to generate high-quality evidence on aetiology for different patient demographics and geographical areas.

A systematic review of the proposed etiologies of the 2021–2022 outbreaks of pediatric acute hepatitis of unknown etiology

In April 2022, the World Health Organization (WHO) declared a global outbreak of acute hepatitis of unknown etiology (AHUE) with a high risk of severe outcomes, for which various etiologies have been proposed by the literature. This study examines primary reports of pediatric AHUE cases and summarizes the proposed etiologies. This systematic review collected and evaluated published peer-reviewed articles, official data, and clinical reports of AHUE cases that met the WHO working case definition. 19 hypothesized etiologies for AHUE were identified from 36 sources, which fell into eight categories. While human adenovirus (HAdV) infection, viral infection, and immune-mediated responses were commonly suspected as causes of AHUE, no definitive etiology or epidemiological link has been established. However, recent evidence implicates adeno-associated virus-2 (AAV2) as a likely significant contributor. Conducting a comprehensive literature review following outbreaks is necessary for developing responsive strategies and protocols.

Paediatric acute hepatitis of unknown aetiology: a national investigation and adenoviraemia case-control study in the UK.

An increase in acute severe hepatitis of unknown aetiology in previously healthy children in the UK in March, 2022, triggered global case-finding. We aimed to describe UK epidemiological investigations of cases and their possible causes. We actively surveilled unexplained paediatric acute hepatitis (transaminase >500 international units per litre) in children younger than 16 years presenting since Jan 1, 2022, through notifications from paediatricians, microbiologists, and paediatric liver units; we collected demographic, clinical, and exposure information. Then, we did a case-control study to investigate the association between adenoviraemia and other viruses and case-status using multivariable Firth penalised logistic regression. Cases aged 1-10 years and tested for adenovirus were included and compared with controls (ie, children admitted to hospital with an acute non-hepatitis illness who had residual blood samples collected between Jan 1 and May 28, 2022, and without known laboratory-confirmed diagnosis or previous adenovirus testing). Controls were frequency-matched on sex, age band, sample months, and nation or supra-region with randomised selection. We explored temporal associations between frequency of circulating viruses identified through routine laboratory pathogen surveillance and occurrence of cases by linear regression. SARS-CoV-2 seropositivity of cases was examined against residual serum from age-matched clinical comparison groups. Between Jan 1 and July 4, 2022, 274 cases were identified (median age 3 years [IQR 2-5]). 131 (48%) participants were male, 142 (52%) were female, and one (<1%) participant had sex data unknown. Jaundice (195 [83%] of 235) and gastrointestinal symptoms (202 [91%] of 222) were common. 15 (5%) children required liver transplantation and none died. Adenovirus was detected in 172 (68%) of 252 participants tested, regardless of sample type; 137 (63%) of 218 samples were positive for adenovirus in the blood. For cases that were successfully genotyped, 58 (81%) of 72 had Ad41F, and 57 were identified as positive via blood samples (six of these were among participants who had undergone a transplant). In the case-control analysis, adenoviraemia was associated with hepatitis case-status (adjusted OR 37·4 [95% CI 15·5-90·3]). Increases in the detection of adenovirus from faecal samples, but not other infectious agents, in routine laboratory pathogen surveillance correlated with hepatitis cases 4 weeks later, which independently suggested an association (β 0·06 [95% CI 0·02-0·11]). No association was identified for SARS-CoV-2 antibody seropositivity. We observed an association between adenovirus 41F viraemia and paediatric acute hepatitis. These results can inform diagnostic testing recommendations, clinical management, and exploratory in vitro or clinical studies of paediatric acute hepatitis of unknown aetiology. The role of potential co-factors, including other viruses and host susceptibility, requires further investigation. None.

The Increase of Mother’s Knowledge and Attitudes After Education with Audio Visual Media About the Prevention of Acute Hepatitis of Unknown Aetiology

Background: In Indonesia, 18 suspected cases of acute hepatitis of unknown aetiology were found on May 11th, 2022. Vigilance efforts were needed by providing education to the public regarding how to prevent the disease. This study aims to determine the increase in mother’s knowledge and attitudes after education with audio visual media about the prevention of acute hepatitis of unknown aetiology. Methods: This study is an analytic descriptive study that was conducted in Ulak Karang Selatan Area of Padang City in April 2023. The study population was all mothers of children under-five in Ulak Karang Selatan Area of Padang City. Sample selection was carried out using consecutive sampling technique consist of 35 people in each group. Results: The results showed that the average percentage of mothers who answered correctly increased from 51.7% to 88.4% after education with audio visual media. In the positive attitude statement, the average percentage of mothers who answered strongly agree increased from 34.0% to 66.6% after education with audio visual media. In the negative attitude statement, the average percentage of mothers who answered strongly disagree increased from 15.7% to 46.6% after education with audio visual media. In the control group, the average percentage of mother’s knowledge and attitudes were not much different between post-test and pre-test. Conclusion: The increase in mother’s knowledge and attitudes regarding the prevention of acute hepatitis of unknown aetiology was higher in intervention group that had been given education with audio visual media than the control group. Keywords: [Knowledge, Attitudes, Audio Visual, Acute Hepatitis]

Severe acute hepatitis of unknown etiology in a large cohort of children.

We evaluated the proportion, clinical features, and outcomes of previously healthy children presenting to a large Canadian quaternary pediatric center with severe acute hepatitis of unknown etiology. All patients with serum alanine aminotransferase (ALT) > 500U/L or aspartate aminotransferase (AST) > 500U/L between June 1, 2018, and May 31, 2022, at The Hospital for Sick Children, were identified. Subjects with only AST > 500U/L were excluded. Clinical characteristics, investigations, and outcomes for patients without clear etiology for ALT > 500U/L (severe acute hepatitis of unknown etiology) for our study period and from October 1 to May 31 of each year 2018-2021 were reviewed. Of 977 patients with ALT/AST> 500U/L, 720 had only ALT > 500U/L. We excluded age below 6 months (n = 99) or above 16 years (n = 66), known pre-existing liver conditions (n = 66), and ALT > 500U/L in already admitted patients (n = 151). Among the remaining 338 children with ALT > 500U/L at presentation, an etiology was identified in 303 subjects. 33 (9.8%) children [median age 6.1y (range 0.5-15.5); 61% male] were confirmed as severe acute hepatitis of unknown etiology. Twenty patients (60.6%) were tested for blood adenovirus by PCR, and 1 (5%) was positive (serotype B7). Liver tissue specimens from 18 patients revealed no evidence of viral inclusions or adenovirus. Twelve (36.3%) presented with pediatric acute liver failure, with 8 (24.2%) requiring liver transplantation. There were no deaths. Hepatitis-associated aplastic anemia occurred in 5 (15%) patients. Of children presenting with severe acute hepatitis to a quaternary children's hospital over a 48-month period, 9.8% had unknown etiology with no change over time. Liver transplantation remains an important treatment strategy for those presenting with pediatric acute liver failure phenotype. The frequency of cases associated with human adenovirus infection was noncontributory.

Task Force for a rapid response to an outbreak of severe acute hepatitis of unknown aetiology in children in Portugal in 2022.

On 5 April 2022, the United Kingdom reported an increase of cases of severe acute hepatitis of unknown aetiology in children, several needing hospitalisation and some required liver transplant or died. Thereafter, 35 countries reported probable cases, almost half of them in Europe. Facing the alert, on 28 April, Portugal created a multidisciplinary Task Force (TF) for rapid detection of probable cases and response. The experts of the TF came from various disciplines: clinicians, laboratory experts, epidemiologists, public health experts and national and international communication. Moreover, Portugal adopted the European Centre for Disease Prevention and Control (ECDC) and the World Health Organization (WHO) case definition and recommendations. By 31 December 2022, 28 probable cases of severe acute hepatitis of unknown aetiology were reported: 16 male and 17 aged under 2 years. Of these cases, 23 were hospitalised but none required liver transplant or died. Adenovirus was detected from nine of 26 tested cases. No association was observed between adenovirus infection and hospital admission after adjusting for age, sex and region in a binomial regression model. The TF in Portugal may have contributed to increase awareness among clinicians, enabling early detection and prompt management of the outbreak.

Recurrent Choledocholithiasis: Unveiling the Diagnostic Challenges of Profound Transaminitis Post Cholecystectomy.

BACKGROUND Profound transaminitis (>1000 international units per liter [IU/L]) is typically associated with ischemic and viral or toxic hepatitis. Pancreaticobiliary causes are less likely to be included in the workup, especially in patients who have undergone cholecystectomy. We present a case of recurrent choledocholithiasis in a 52-year-old woman 7 years after cholecystectomy, presenting with severe transaminitis, illustrating the diagnostic challenges of this presentation. CASE REPORT A 52-year-old woman presented to the Emergency Department (ED) with acute upper abdominal pain. Computed tomography (CT) of the abdomen without contrast showed no abnormalities and mild common bile duct (CBD) dilation was noted on ultrasound (US) abdomen. Laboratory studies were significant for elevated transaminases greater than 1000 units/L and alkaline phosphatase (ALP) greater than 200 units/L. She was diagnosed with acute hepatitis of unknown etiology without undergoing further investigation of the biliary tract and was discharged after improvement with supportive therapy. She returned 4 months later with similar symptoms and laboratory findings, but with more CBD dilation and intrahepatic biliary dilation on CT and US. Endoscopic retrograde cholangiopancreatography (ERCP) was performed, and multiple stones and sludge were removed from the CBD. CONCLUSIONS This report has shown that pancreaticobiliary causes should be included in the workup of severe transaminitis, even in patients with a remote history of cholecystectomy. Failure to do so may subject patients to extensive, unnecessary workup and delay correct management.

The Effectiveness of Education with Audio Visual Media on Mother’s Knowledge and Attitudes About Acute Hepatitis of Unknown Aetiology

Background: Hepatitis is a disease characterized by inflammation of the liver. It can cause liver failure. Health education plays an important role as one of the promotive and preventive efforts of acute hepatitis by increasing mother’s knowledge and attitudes. This study aims to determine the effectiveness of education with audio visual media on mother’s knowledge and attitudes about acute hepatitis of unknown aetiology in Ulak Karang Selatan Area, Padang City. Methods: This is a quasi-experimental study with non-equivalent control group design. This study was conducted in two Posyandu namely Posyandu Cinta Sehat 11 and Posyandu Cinta Sehat 16 which began in June 2022 to June 2023. Sample selection was carried out using consecutive sampling technique. The total sample was 35 people in each group. Results: The results showed that there was a difference in the mean posttest of mother’s knowledge between intervention group and control group (p&lt;0.001). Mean gain of mother’s knowledge in intervention group was significantly different from control group (p&lt;0.001). There was a difference in the mean posttest of mother’s attitude between intervention group and control group (p&lt;0.001). Mean gain of mother’s attitude in intervention group was significantly different from control group (p&lt;0.001). Conclusion: Education with audio visual media was proven effective in improving mother’s knowledge and attitudes about acute hepatitis of unknown aetiology. Health workers at Ulak Karang Health Center can use audio visual media as a tool in providing effective health education to improve mother’s knowledge and attitudes about acute hepatitis of unknown aetiology in their working area. Keywords: [Acute Hepatitis, Attitudes, Audio Visual, Knowledge]

Acute hepatitis of unknown etiology in an adult female: A case report

In recent years, because of the growing desire to improve the noninvasiveness and safety of tumor treatments, sonodynamic therapy has gradually become a popular research topic. However, due to the complexity of the therapeutic process, the relevant mechanisms have not yet been fully elucidated. One of the widely accepted possibilities involves the effect of reactive oxygen species. In this review, the mechanism of reactive oxygen species production by sonodynamic therapy (SDT) and ways to enhance the sonodynamic production of reactive oxygen species are reviewed. Then, the clinical application and limitations of SDT are discussed. In conclusion, current research on sonodynamic therapy should focus on the development of sonosensitizers that efficiently produce active oxygen, exhibit biological safety, and promote the clinical transformation of sonodynamic therapy.

Signatures of AAV-2 immunity are enriched in children with severe acute hepatitis of unknown etiology.

Severe acute hepatitis of unknown etiology in children is under investigation in 35 countries. Although several potential etiologic agents have been investigated, a clear cause for the liver damage observed in these cases remains to be identified. Using VirScan, a high-throughput antibody profiling technology, we probed the antibody repertoires of nine cases of severe acute hepatitis of unknown etiology treated at Children's of Alabama and compared their antibody responses with 38 pediatric and 470 adult controls. We report increased adeno-associated dependoparvovirus A (AAV-A) breadth in cases relative to controls and adeno-associated virus 2 (AAV-2) peptide responses that were conserved in seven of nine cases but rarely observed in pediatric and adult controls. These findings suggest that AAV-2 is a likely etiologic agent of severe acute hepatitis of unknown etiology.

Investigation of acute severe hepatitis in children: A review of liver transplant data, Canada, 2021-2022.

An increase in severe acute hepatitis of unknown etiology was first reported in the United Kingdom in April 2022. Following this report, the Public Health Agency of Canada connected with three paediatric liver transplant centres across Canada to determine if an increase in liver transplants was noted. Data demonstrated no observable increase in the number of transplants conducted in 2022. These data in conjunction with a federal, provincial, territorial investigation provided insight into the situation in Canada.

Clinicopathologic Features of Severe Acute Hepatitis Associated With Adenovirus Infection in Children.

A recent increase in reports of severe acute hepatitis of unknown etiology in children is under investigation. Although adenovirus has been frequently detected, its role remains unclear, and systematic histopathologic analysis is lacking. We conducted a retrospective study of 11 children hospitalized between October 2021 and May 2022 with unexplained acute hepatitis and concurrent adenovirus infection. Liver biopsies collected shortly after admission demonstrated moderately to severely active hepatitis in 8/11 (73%) cases, characterized by marked portal mixed inflammation, moderate-to-severe interface activity, and milder lobular inflammation. Clusters of plasma cells were present in 6/11 (55%) cases, mimicking autoimmune hepatitis. Semiquantitative scoring of 17 discrete histologic features found that greater degrees of portal inflammation, interface activity, bile duct injury, bile ductular reaction, lobular inflammation, Kupffer cell activation, and hepatocyte focal necrosis were significantly more common in these cases in comparison to the control group of unexplained acute severe hepatitis without adenovirus infection. Liver biopsy immunohistochemistry was negative for adenovirus in all cases. Polymerase chain reaction testing of liver tissue was positive for the enteric adenovirus serotypes 41 (species F) in 10/11 (91%) cases. An immunoprofile study of hepatic infiltrating lymphocytes in 1 patient revealed the presence of large numbers of CD3 + and CD4 + lymphocytes. Nine patients received supportive treatment without steroids and recovered without the need for liver transplantation. In summary, liver injury in children with severe acute hepatitis and adenovirus infection is characterized by a hepatitic pattern that resembles severe autoimmune hepatitis and may represent an immune-mediated process associated with viral infection.

National Surveillance of Pediatric Acute Hepatitis of Unknown Etiology, Japan, October 2021–December 2022

Pediatric acute hepatitis of unknown etiology has been reported globally since April 2022. In Japan, 139 possible cases with onset dates after October 2021 were reported as of December 2022. Three patients required liver transplants, but none died. Rates of adenovirus positivity (11/125, 9%) were lower than those for other countries.