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The American Journal of Surgical... Sep 2023A recent increase in reports of severe acute hepatitis of unknown etiology in children is under investigation. Although adenovirus has been frequently detected, its role...
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.
Topics: Humans; Child; Hepatitis, Autoimmune; Retrospective Studies; Liver; Inflammation; Adenoviridae Infections; CD4-Positive T-Lymphocytes
PubMed: 37357941
DOI: 10.1097/PAS.0000000000002084 -
Viruses Sep 2023Hepatitis A virus (HAV) and hepatitis E virus (HEV) infections often present as acute hepatitis with prodromal symptoms. These infections, transmitted via the...
Hepatitis A virus (HAV) and hepatitis E virus (HEV) infections often present as acute hepatitis with prodromal symptoms. These infections, transmitted via the oral-enteral route, constitute significant public health challenges, particularly in developing countries with subpar sanitary systems. The aim of the study was to describe the clinical manifestations, laboratory findings, and outcomes of hepatitis A and hepatitis E infections in Thailand. We conducted a retrospective chart review and analysis of 152 patients diagnosed with acute hepatitis A or hepatitis E from January 2007 to August 2018 at Siriraj Hospital. The hepatitis E cohort was older with a greater prevalence of comorbidities (hypertension, diabetes mellitus, chronic kidney disease, chronic hepatitis B, and post-kidney transplantation status) than the hepatitis A cohort. While the majority of hepatitis A patients presented with fever (98%) and jaundice (96%), these symptoms were less pronounced in hepatitis E patients. Furthermore, hepatitis A patients exhibited significantly higher aminotransferase and total bilirubin levels. However, clinical outcomes, such as hospitalization rates, progression to acute liver failure, and mortality, were comparable across both groups. In conclusion, although the clinical manifestations of hepatitis A and hepatitis E were similar, fever and jaundice were more prevalent and aminotransferase and bilirubin levels were higher in the HAV-infected group.
Topics: Humans; Hepatitis A; Hepatitis E; Thailand; Retrospective Studies; Hepatitis A virus; Hepatitis E virus; Fever; Bilirubin
PubMed: 37766294
DOI: 10.3390/v15091888 -
Hepatology Communications Oct 2023We evaluated the proportion, clinical features, and outcomes of previously healthy children presenting to a large Canadian quaternary pediatric center with severe acute...
BACKGROUND
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.
METHODS
All patients with serum alanine aminotransferase (ALT) > 500 U/L or aspartate aminotransferase (AST) > 500 U/L between June 1, 2018, and May 31, 2022, at The Hospital for Sick Children, were identified. Subjects with only AST > 500 U/L were excluded. Clinical characteristics, investigations, and outcomes for patients without clear etiology for ALT > 500 U/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.
RESULTS
Of 977 patients with ALT/AST> 500 U/L, 720 had only ALT > 500 U/L. We excluded age below 6 months (n = 99) or above 16 years (n = 66), known pre-existing liver conditions (n = 66), and ALT > 500 U/L in already admitted patients (n = 151). Among the remaining 338 children with ALT > 500 U/L at presentation, an etiology was identified in 303 subjects. 33 (9.8%) children [median age 6.1 y (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.
CONCLUSIONS
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.
Topics: Humans; Child; Male; Infant; Female; Canada; Hepatitis; Hepatitis A; Acute Disease; Liver Failure, Acute
PubMed: 37756118
DOI: 10.1097/HC9.0000000000000272 -
Liver International : Official Journal... Jun 2024Acute hepatitis E (AHE) is still a public health issue worldwide. Here, we report the global burden of AHE in 204 countries and territories from 1990 to 2019 by age, sex...
BACKGROUND AND AIMS
Acute hepatitis E (AHE) is still a public health issue worldwide. Here, we report the global burden of AHE in 204 countries and territories from 1990 to 2019 by age, sex and socio-demographic index (SDI), and predict the future trends to 2030.
METHODS
Data on AHE were collected from the Global Burden of Diseases, Injuries and Risk Factors Study 2019. The average annual percentage change (AAPC) and joinpoint analysis were used to determine the burden trend.
RESULTS
In 2019, there were 19.47 million (95% UI, 16.04 to 23.37 million) incident cases of AHE globally, with a 19% increase since 1990. Age-standardized rate (ASR) of disability-adjusted life years (DALYs), prevalent and incident cases declined from 1990 to 2019. In 2019, the ASR of incidence, prevalence and DALYs due to HEV infection were highest in the same regions of South Asia for both sexes. Southern Sub-Saharan Africa presented the highest increases in the ASR for incidence of HEV infection in both males (AAPC = .25) and females (AAPC = .24) from 1990 to 2019. Incident cases are higher in males than females before 55-59 years old. The SDI values were negatively correlated with the age-standardized DALYs. Between 2019 and 2030, the ASR for incidence and prevalence of HEV for both sexes showed an increasing trend.
CONCLUSIONS
Although the overall ASR of AHE decreased, the burden of AHE remains an underappreciated problem for society. The findings may provide useful information for policymakers to develop appropriate strategies aimed at reducing the burden of AHE.
Topics: Humans; Male; Female; Hepatitis E; Middle Aged; Adult; Global Burden of Disease; Incidence; Disability-Adjusted Life Years; Prevalence; Adolescent; Global Health; Young Adult; Aged; Child, Preschool; Child; Infant; Risk Factors; Age Distribution; Sex Distribution; Acute Disease; Infant, Newborn
PubMed: 38426633
DOI: 10.1111/liv.15883 -
Clinics in Liver Disease Nov 2023The natural history of hepatitis B virus (HBV) infection is closely dependent on the dynamic interplay between the host immune response and viral replication.... (Review)
Review
The natural history of hepatitis B virus (HBV) infection is closely dependent on the dynamic interplay between the host immune response and viral replication. Spontaneous HBV clearance in acute self-limited infection is the result of an adequate and efficient antiviral immune response. Instead, it is widely recognized that in chronic HBV infection, immunologic dysfunction contributes to viral persistence. Long-lasting exposure to high viral antigens, upregulation of multiple co-inhibitory receptors, dysfunctional intracellular signaling pathways and metabolic alterations, and intrahepatic regulatory mechanisms have been described as features ultimately leading to a hierarchical loss of effector functions up to full T-cell exhaustion.
Topics: Humans; Hepatitis B virus; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Hepatitis B; Virus Replication
PubMed: 37778772
DOI: 10.1016/j.cld.2023.05.001 -
PLoS Pathogens Sep 2023Hepatitis E virus (HEV) causes self-limited acute hepatitis in immunocompetent individuals and can establish chronic infection in solid organ transplant recipients...
Hepatitis E virus (HEV) causes self-limited acute hepatitis in immunocompetent individuals and can establish chronic infection in solid organ transplant recipients taking immunosuppressive drugs. A well characterized small animal model is needed to understand HEV pathogenesis. In this study, we established a robust model to study acute and persistent HEV infection using Mongolian gerbils (Meriones unguiculatus) with or without immunosuppression. Gerbils were implanted subcutaneously with continuous release tacrolimus pellet to induce immunosuppression. Gerbils with or without tacrolimus treatment were inoculated with HEV intraperitoneally. Viremia, fecal virus shedding, serum antibody and ALT levels, liver histopathological lesions, hepatocyte apoptosis, and liver macrophage distribution were assessed. Mild to moderate self-limited hepatitis and IgM and IgG antibody responses against HEV ORF2 were observed in immunocompetent gerbils. Levels of HEV-specific IgM responses were higher and lasted longer in immunocompetent gerbils with higher peak viremia. Persistent viremia and fecal virus shedding with either weak, or absent HEV antibody levels were seen in immunosuppressed gerbils. Following HEV infection, serum ALT levels were increased, with lower and delayed peaks observed in immunosuppressed compared to immunocompetent gerbils. In immunocompetent gerbils, foci of apoptotic hepatocytes were detected that were distributed with inflammatory infiltrates containing CD68+ macrophages. However, these foci were absent in immunosuppressed gerbils. The immunosuppressed gerbils showed no inflammation with no increase in CD68+ macrophages despite high virus replication in liver. Our findings suggest adaptive immune responses are necessary for inducing hepatocyte apoptosis, CD68+ macrophage recruitment, and inflammatory cell infiltration in response to HEV infection. Our studies show that Mongolian gerbils provide a promising model to study pathogenesis during acute and persistent HEV infection.
Topics: Animals; Humans; Hepatitis E virus; Gerbillinae; Tacrolimus; Viremia; Hepatitis E; Genotype
PubMed: 37703304
DOI: 10.1371/journal.ppat.1011664 -
JAMA May 2024
Topics: Humans; Acute Disease; Hepatitis D; Hepatitis D, Chronic; Hepatitis Delta Virus; Risk Factors; Hepatitis B; Coinfection; Vaccination; Viral Vaccines
PubMed: 38635231
DOI: 10.1001/jama.2024.1317 -
MMWR. Recommendations and Reports :... Nov 2023The elimination of hepatitis C is a national priority (https://www.hhs.gov/sites/default/files/Viral-Hepatitis-National-Strategic-Plan-2021-2025.pdf). During 2010-2021,...
The elimination of hepatitis C is a national priority (https://www.hhs.gov/sites/default/files/Viral-Hepatitis-National-Strategic-Plan-2021-2025.pdf). During 2010-2021, hepatitis C virus (HCV) acute and chronic infections (hereinafter referred to as HCV infections) increased in the United States, consequences of which include cirrhosis, liver cancer, and death. Rates of acute infections more than tripled among reproductive-aged persons during this time (from 0.8 to 2.5 per 100,000 population among persons aged 20-29 years and from 0.6 to 3.5 among persons aged 30-39 years). Because acute HCV infection can lead to chronic infection, this has resulted in increasing rates of HCV infections during pregnancy. Approximately 6%-7% of perinatally exposed (i.e., exposed during pregnancy or delivery) infants and children will acquire HCV infection. Curative direct-acting antiviral therapy is approved by the Food and Drug Administration for persons aged ≥3 years. However, many perinatally infected children are not tested or linked to care. In 2020, because of continued increases in HCV infections in the United States, CDC released universal screening recommendations for adults, which included recommendations for screening for pregnant persons during each pregnancy (Schillie S, Wester C, Osborne M, Wesolowski L, Ryerson AB. CDC recommendations for hepatitis C screening among adults-United States, 2020. MMWR Recomm Rep 2020;69[No. RR-2]:1-17). This report introduces four new CDC recommendations: 1) HCV testing of all perinatally exposed infants with a nucleic acid test (NAT) for detection of HCV RNA at age 2-6 months; 2) consultation with a health care provider with expertise in pediatric hepatitis C management for all infants and children with detectable HCV RNA; 3) perinatally exposed infants and children with an undetectable HCV RNA result at or after age 2 months do not require further follow-up unless clinically warranted; and 4) a NAT for HCV RNA is recommended for perinatally exposed infants and children aged 7-17 months who previously have not been tested, and a hepatitis C virus antibody (anti-HCV) test followed by a reflex NAT for HCV RNA (when anti-HCV is reactive) is recommended for perinatally exposed children aged ≥18 months who previously have not been tested. Proper identification of perinatally infected children, referral to care, and curative treatment are critical to achieving the goal of hepatitis C elimination.
Topics: Adult; Pregnancy; Female; Child; Humans; United States; Infant; Antiviral Agents; Hepatitis C, Chronic; Hepatitis C; Hepacivirus; RNA; Persistent Infection; Centers for Disease Control and Prevention, U.S.
PubMed: 37906518
DOI: 10.15585/mmwr.rr7204a1 -
Clinics in Liver Disease Aug 2023Acute on chronic liver failure (ACLF) is a unique disease process associated with significant short-term mortality wherein patients with either chronic liver disease or... (Review)
Review
Acute on chronic liver failure (ACLF) is a unique disease process associated with significant short-term mortality wherein patients with either chronic liver disease or cirrhosis suffer rapid decompensation in hepatic function accompanied by extrahepatic organ failures. Alcohol-associated hepatitis (AH) is a common precipitant of ACLF and has been shown to uniquely affect the pathophysiology of systemic and hepatic immune responses in patients with ACLF. Treatment of AH-associated ACLF includes supportive measures as well as treatment directed at AH; however, AH-directed therapies unfortunately remain limited and are of suboptimal efficacy.
Topics: Humans; Acute-On-Chronic Liver Failure; Hepatitis, Alcoholic; Liver Cirrhosis
PubMed: 37380289
DOI: 10.1016/j.cld.2023.03.009 -
The Science of the Total Environment Jan 2024Wastewater pathogen monitoring is useful for surveillance of enteric pathogens. Information about the presence of Paslahepevirus balayani (HEV) and emergent...
BACKGROUND
Wastewater pathogen monitoring is useful for surveillance of enteric pathogens. Information about the presence of Paslahepevirus balayani (HEV) and emergent Rocahepevirus ratti (RHEV) in untreated water and their correlation with clinical cases is scarce. Aim To longitudinally monitor HEV and RHEV in wastewater and to evaluate their possible correlation with human cases.
METHODS
This study was carried out in the city of Cordoba (southern Spain) from March 2021 to March 2023. HEV and RHEV occurrence were evaluated by PCR in three sample types: i) sera from patients with acute hepatitis attended at the reference hospital, ii) liver and faeces from urban rodents, and iii) grab sewage samples collected weekly from the municipal wastewater treatment plant.
RESULTS
We analysed 106 untreated wastewater samples, 304 individuals with acute hepatitis, and 20 rodents. HEV and RHEV were detected in only one (0.9 %) and almost all samples (94.3 %) of wastewater samples, respectively. A total of 22 cases of acute HEV infection (7.2 %) and two cases of RHEV (0.7 %) were detected from all acute hepatitis cases observed. Only RHEV was found in rodents, with a positive frequency of 55 %. The presence of HEV in wastewater coincided with the detection of one case in which the same HEV genotype was isolated. A concentration of HEV clinical cases between June and July of 2022 was observed but not detected in water. Both RHEV clinical cases were detected in summer 2022, but no correlation was found with wastewater detection.
CONCLUSIONS
Our study shows that there is no correlation between clinical cases and wastewater detection of HEV or RHEV.
Topics: Humans; Animals; Rats; Hepatitis E; Hepatitis E virus; Wastewater; Water
PubMed: 37914110
DOI: 10.1016/j.scitotenv.2023.168203