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Journal of Viral Hepatitis Jun 2021Hepatitis A virus (HAV) infection causes an acute enteric hepatitis associated with substantial morbidity and mortality, particularly in older individuals. Incidence of...
Hepatitis A virus (HAV) infection causes an acute enteric hepatitis associated with substantial morbidity and mortality, particularly in older individuals. Incidence of HAV infection is low in the United States, mostly related to consumption of contaminated food. Starting in 2017, Indiana reported a large HAV outbreak. We sought to characterize the risk-exposures, clinical features and outcomes of HAV and examine the differences based on underlying cirrhosis and age. Adults ≥18 years diagnosed with HAV between January 2017 and April 2019 at two large healthcare systems in Indiana were identified. Demographic data, risk-exposures, clinical features, laboratory data and clinical outcomes were collected for analysis. The HAV cohort constituted 264 individuals with mean age of 41-years, 62% male and 94% Caucasian. Risk-exposures identified were illicit drug use (74%), food-borne (15%), person-to-person (11%) and incarceration (11%). Mortality rate was 2%, acute liver failure (ALF) was seen in 4% and acute on chronic liver failure (ACLF) was seen in 30% (6 of 20 with underlying cirrhosis). Admission MELD score was the only factor associated with ALF [OR = 1.17 (1.08-1.2), p < 0.0001], on multivariable logistic regression analysis. Higher proportion of individuals with underlying cirrhosis developed acute kidney injury (AKI) (26% vs. 9%, p = 0.03), ascites (45% vs. 11%, p < 0.0001) and hepatic encephalopathy (35% vs. 4%, p < 0.0001). In conclusion, illicit drug use was the predominant risk-exposure in the current HAV outbreak, which was associated with 2% mortality rate, and those with cirrhosis had worse outcomes (AKI, ascites and HE), of whom 30% developed ACLF.
Topics: Acute-On-Chronic Liver Failure; Adult; Aged; Disease Outbreaks; Female; Hepatitis A; Humans; Indiana; Liver Cirrhosis; Male
PubMed: 33763937
DOI: 10.1111/jvh.13504 -
Water Research Aug 2023Monitoring wastewater is an effective tool for tracking information on trends of enteric viral dissemination. This study aimed to perform molecular detection and genetic...
Monitoring wastewater is an effective tool for tracking information on trends of enteric viral dissemination. This study aimed to perform molecular detection and genetic characterization of HAV in wastewater and to correlate the results with those obtained from clinical surveillance. Wastewater samples (n=811) of the second most populous city in Argentina were collected from the main wastewater treatment plant (BG-WWTP, n=261), and at 7 local neighborhood collector sewers (LNCS, n=550) during 2017-2022. Clinical samples of acute hepatitis A cases (HA, n=54) were also analyzed. HAV molecular detection was performed by real time RT-PCR, and genetic characterization by RT-Nested PCR, sequencing and phylogenetic analysis. RNA-HAV was detected in sewage samples throughout the entire period studied, and detection frequencies varied according to the location and year (2.9% - 56.5%). In BG-WWTP, 23% of the samples were RNA-HAV+. The highest detection rates were in 2017 (30.0%), 2018 (41.7%) and 2022 (56.5%), which coincides with the highest number of HA cases reported. Twenty-eight (28) sequences were obtained (from clinical and sewage samples), and all were genotype IA. Two monophyletic clusters were identified: one that grouped clinical and wastewater samples from 2017-2018, and another with specimens from 2022, evidencing that environmental surveillance might constitute a replica of viral circulation in the population. These findings evidence that WBE, in a centralized and decentralized sewage monitoring, might be an effective strategy to track HAV circulation trends over time, contributing to the knowledge of HAV in the new post-vaccination epidemiological scenarios in Argentina and in Latin America.
Topics: Humans; Hepatitis A virus; Wastewater; Sewage; Phylogeny; Hepatitis A; RNA; Real-Time Polymerase Chain Reaction; RNA, Viral
PubMed: 37262946
DOI: 10.1016/j.watres.2023.120102 -
Viruses Feb 2020One patient presented hyporexia, asthenia, adynamia, and jaundice two months after acute yellow fever (YF) onset; plus laboratory tests indicating hepatic cytolysis and...
One patient presented hyporexia, asthenia, adynamia, and jaundice two months after acute yellow fever (YF) onset; plus laboratory tests indicating hepatic cytolysis and a rebound of alanine and aspartate transaminases, and total and direct bilirubin levels. Laboratory tests discarded autoimmune hepatitis, inflammatory or metabolic liver disease, and new infections caused by hepatotropic agents. Anti-YFV IgM, IgG and neutralizing antibodies were detected in different times, but no viremia. A liver biopsy was collected three months after YF onset and tested positive for YFV antigens and wild-type YFV-RNA (364 RNA-copies/gram/liver). Transaminases and bilirubin levels remained elevated for five months, and the arresting of symptoms persisted for six months after the acute YF onset. Several serum chemokines, cytokines, and growth factors were measured. A similar immune response profile was observed in the earlier phases of the disease, followed by more pronounced changes in the later stages, when transaminases levels returned to normal. The results indicated viral persistence in the liver and continual liver cell damage three months after YF onset and reinforced the need for extended follow-ups of YF patients. Further studies to investigate the role of possible viral persistence and the immune response causing relapsing hepatitis following YF are also necessary.
Topics: Acute Disease; Antibodies, Neutralizing; Antibodies, Viral; Biopsy; Cytokines; Hepatitis A; Humans; Jaundice; Liver; Liver Function Tests; Male; Middle Aged; Recurrence; Time Factors; Yellow Fever; Yellow fever virus
PubMed: 32079143
DOI: 10.3390/v12020222 -
The Journal of General Virology Nov 2022Over the past few months there have been reports of severe acute hepatitis in several hundred, otherwise healthy, immunocompetent young children. Several deaths have...
Over the past few months there have been reports of severe acute hepatitis in several hundred, otherwise healthy, immunocompetent young children. Several deaths have been recorded and a relatively large proportion of the patients have needed liver transplants. Most of the cases, so far, have been seen in the UK and in North America, but it has also been reported in many other European countries, the Middle East and Asia. Most common viruses have been ruled out as a causative agent; hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) were not detected, nor were Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human immunodeficiency virus (HIV) in many cases. A small proportion of the children had been infected with SARS-CoV-2 but these seem to be in a minority; similarly, almost none of the children had been vaccinated against COVID-19. Significantly, many of the patients were infected with adenovirus 41 (HAdV-F41). Previously, HAdV-41 had not been linked to hepatitis and is usually considered to cause gastroenteritis in both immunocompetent and immunocompromised patients. In two most recent studies, adeno-associated virus 2 (AAV2) was detected in almost all patients, together with species C and F HAdVs and human herpesvirus 6B (HHV6B). Here, I discuss the possibility that a change in tropism of HAdV-41 and changes in AAV2 may be responsible for their links to acute hepatitis.
Topics: Child; Humans; Child, Preschool; Adenoviridae; Herpesvirus 4, Human; Epstein-Barr Virus Infections; SARS-CoV-2; COVID-19; Adenoviridae Infections; Parvovirinae; Hepatitis
PubMed: 36367762
DOI: 10.1099/jgv.0.001783 -
Annals of Global Health Mar 2020Hepatitis A virus (HAV) and hepatitis E virus (HEV) are transmitted by the fecal-oral route and are responsible for epidemic and sporadic outbreaks of acute hepatitis in...
BACKGROUND
Hepatitis A virus (HAV) and hepatitis E virus (HEV) are transmitted by the fecal-oral route and are responsible for epidemic and sporadic outbreaks of acute hepatitis in low-income countries like Bangladesh.
OBJECTIVE
The purpose of this study was to describe the seroprevalence of acute hepatitis due to HAV and HEV infection in Bangladesh.
METHODS
The nationwide food-borne illness surveillance started in 2014 at 10 different hospitals which covered seven divisions of Bangladesh. Blood samples were collected from suspected acute hepatitis cases and screened for the anti-HAV IgM and anti-HEV IgM using enzyme-linked immunosorbent assay (ELISA). Participants' socioeconomic status, clinical, sanitation and food history were recorded. Multivariate logistic regression was performed to determine the risk factors associated with HAV and HEV infection.
FINDINGS
A total of 998 patients were enrolled and tested for both HAV and HEV. Among these, 19% (191/998) were identified as HAV positive and 10% (103/998) were HEV positive. The median age was 12 years and 25 years for HAV and HEV positive patients, respectively. The prevalence of HAV was higher among the females (24.9%), whereas HEV was higher among males (11.2%). The highest occurrence of HAV was observed among children while HEV was most prevalent in the 15-60 years age group (12.4%).
CONCLUSION
Through our nationwide surveillance, it is evident that hepatitis A and hepatitis E infection is common in Bangladesh. These data will be useful towards planning preventive and control measures by strengthening the sanitation programs and vaccination strategies in Bangladesh.
Topics: Acute Disease; Adolescent; Adult; Age Distribution; Bangladesh; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Female; Hepatitis A; Hepatitis A Antibodies; Hepatitis Antibodies; Hepatitis E; Humans; Immunoglobulin M; Infant; Infant, Newborn; Logistic Models; Male; Middle Aged; Multivariate Analysis; Prevalence; Seroepidemiologic Studies; Sex Distribution; Young Adult
PubMed: 32211299
DOI: 10.5334/aogh.2574 -
European Journal of Gastroenterology &... Dec 2021Patients with acute hepatitis A virus (HAV) infection are at risk of developing acute kidney injury (AKI) which may result in increased healthcare resource utilization...
BACKGROUND
Patients with acute hepatitis A virus (HAV) infection are at risk of developing acute kidney injury (AKI) which may result in increased healthcare resource utilization and worse clinical outcomes. We investigated the impact of AKI on healthcare utilization and clinical outcomes in patients hospitalized with acute HAV infection utilizing a large database.
METHODS
We queried the National Inpatient Sample (NIS) 2007-2014 to identify acute HAV infection-related hospitalizations with and without AKI. Primary outcomes were prevalence of AKI and its predictors with secondary outcomes included the mean length of stay (LOS), hospitalization cost and mortality in both groups.
RESULTS
Out of 68 364 acute HAV infection-related hospitalizations, 47 620 met our study criteria and 7458 (15.7%) had concurrent AKI. HAV patients with AKI were older (62.5 vs. 53.7 years; P value <0.001). A higher mean LOS (10.03 vs. 5.6 days; P value <0.001) and mean total hospitalization cost ($27 171.35 vs. $12 790.26; P value <0.001) were observed in HAV patients with the AKI group. A total of 1032 patients (13.8%) in the AKI group died during the same hospitalization as compared to 681 patients (1.5%) in the non-AKI group, P value <0.001. AKI in HAV was also found to be an independent predictor of mortality [adjusted odds ratio (aOR), 3.28; 95% confidence interval, 2.23-4.84; P value <0.001) after adjusting for the confounding factors.
CONCLUSION
We found that 15.67% of patients hospitalized with acute HAV had AKI which contributed to increased healthcare utilization and higher mortality which is preventable.
Topics: Acute Kidney Injury; Hepatitis A; Hepatitis A virus; Hospital Mortality; Hospitalization; Humans; Length of Stay; Patient Acceptance of Health Care; Retrospective Studies; Risk Factors
PubMed: 34138764
DOI: 10.1097/MEG.0000000000002230 -
Hepatology (Baltimore, Md.) Dec 2022A few case reports of autoimmune hepatitis-like liver injury have been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. We...
BACKGROUND AND AIMS
A few case reports of autoimmune hepatitis-like liver injury have been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. We evaluated clinical features, treatment response and outcomes of liver injury following SARS-CoV-2 vaccination in a large case series.
APPROACH AND RESULTS
We collected data from cases in 18 countries. The type of liver injury was assessed with the R-value. The study population was categorized according to features of immune-mediated hepatitis (positive autoantibodies and elevated immunoglobulin G levels) and corticosteroid therapy for the liver injury. We identified 87 patients (63%, female), median age 48 (range: 18-79) years at presentation. Liver injury was diagnosed a median 15 (range: 3-65) days after vaccination. Fifty-one cases (59%) were attributed to the Pfizer-BioNTech (BNT162b2) vaccine, 20 (23%) cases to the Oxford-AstraZeneca (ChAdOX1 nCoV-19) vaccine and 16 (18%) cases to the Moderna (mRNA-1273) vaccine. The liver injury was predominantly hepatocellular (84%) and 57% of patients showed features of immune-mediated hepatitis. Corticosteroids were given to 46 (53%) patients, more often for grade 3-4 liver injury than for grade 1-2 liver injury (88.9% vs. 43.5%, p = 0.001) and more often for patients with than without immune-mediated hepatitis (71.1% vs. 38.2%, p = 0.003). All patients showed resolution of liver injury except for one man (1.1%) who developed liver failure and underwent liver transplantation. Steroid therapy was withdrawn during the observation period in 12 (26%) patients after complete biochemical resolution. None had a relapse during follow-up.
CONCLUSIONS
SARS-CoV-2 vaccination can be associated with liver injury. Corticosteroid therapy may be beneficial in those with immune-mediated features or severe hepatitis. Outcome was generally favorable, but vaccine-associated liver injury led to fulminant liver failure in one patient.
Topics: Male; Humans; Female; Middle Aged; SARS-CoV-2; COVID-19 Vaccines; COVID-19; ChAdOx1 nCoV-19; BNT162 Vaccine; Vaccination; Hepatitis A; Hepatitis, Autoimmune
PubMed: 35567545
DOI: 10.1002/hep.32572 -
Pathogenicity and virulence of human adenovirus F41: Possible links to severe hepatitis in children.Virulence Dec 2023Over 100 human adenoviruses (HAdVs) have been isolated and allocated to seven species, A-G. Species F comprises two members-HAdV-F40 and HAdV-F41. As their primary site... (Review)
Review
Over 100 human adenoviruses (HAdVs) have been isolated and allocated to seven species, A-G. Species F comprises two members-HAdV-F40 and HAdV-F41. As their primary site of infection is the gastrointestinal tract they have been termed, with species A, enteric adenoviruses. HAdV-F40 and HAdV-F41 are a common cause of gastroenteritis and diarrhoea in children. Partly because of difficulties in propagating the viruses in the laboratory, due to their restrictions on growth in many cell lines, our knowledge of the properties of individual viral proteins is limited. However, the structure of HAdV-F41 has recently been determined by cryo-electron microscopy. The overall structure is similar to those of HAdV-C5 and HAdV-D26 although with some differences. The sequence and arrangement of the hexon hypervariable region 1 (HVR1) and the arrangement of the C-terminal region of protein IX differ. Variations in the penton base and hexon HVR1 may play a role in facilitating infection of intestinal cells by HAdV-F41. A unique feature of HAdV-F40 and F41, among human adenoviruses, is the presence and expression of two fibre genes, giving long and short fibre proteins. This may also contribute to the tropism of these viruses. HAdV-F41 has been linked to a recent outbreak of severe acute hepatitis "of unknown origin" in young children. Further investigation has shown a very high prevalence of adeno-associated virus-2 in the liver and/or plasma of some cohorts of patients. These observations have proved controversial as HAdV-F41 had not been reported to infect the liver and AAV-2 has generally been considered harmless.
Topics: Humans; Child; Child, Preschool; Adenoviruses, Human; Virulence; Cryoelectron Microscopy; Adenovirus Infections, Human; Hepatitis; Hepatitis A; Phylogeny
PubMed: 37543996
DOI: 10.1080/21505594.2023.2242544 -
Cold Spring Harbor Perspectives in... Jan 2019Mechanistic analyses of hepatitis A virus (HAV)-induced pathogenesis have long been thwarted by the lack of tractable small animal models that recapitulate disease... (Review)
Review
Mechanistic analyses of hepatitis A virus (HAV)-induced pathogenesis have long been thwarted by the lack of tractable small animal models that recapitulate disease observed in humans. Several approaches have shown success, including infection of chimeric mice with human liver cells. Other recent studies show that HAV can replicate to high titer in mice lacking expression of the type I interferon (IFN) receptor (IFN-α/β receptor) or mitochondrial antiviral signaling (MAVS) protein. Mice deficient in the IFN receptor show critical features of type A hepatitis in humans when challenged with human HAV, including histological evidence of liver damage, leukocyte infiltration, and the release of liver enzymes into blood. Acute pathogenesis is caused by MAVS-dependent signaling that leads to intrinsic apoptosis of hepatocytes.
Topics: Adaptor Proteins, Signal Transducing; Animals; Disease Models, Animal; Hepatitis A; Hepatitis A virus; Hepatocytes; Humans; Liver; Mice; Mice, Inbred C57BL; Signal Transduction
PubMed: 29661811
DOI: 10.1101/cshperspect.a031674 -
Health state utilities of patients with hepatitis B and C and hepatitis-related conditions in Japan.Scientific Reports Oct 2022Health state utilities are global measurements of quality of life and have been used to evaluate health outcomes for the cost-utility analysis. This study aimed to...
Health state utilities are global measurements of quality of life and have been used to evaluate health outcomes for the cost-utility analysis. This study aimed to estimate the health state utilities of patients with hepatitis B (HB), hepatitis C (HC), and hepatitis-related diseases in Japan. We distributed a self-administered questionnaire, including the EuroQol 5-Dimension 5-Level (EQ-5D-5L), to 9,952 outpatients with several clinical conditions caused by HB or HC virus infection (such as asymptomatic chronic hepatitis, chronic hepatitis, compensated cirrhosis, and decompensated cirrhosis) and estimated the condition-specific utilities of patients with HB or HC. In patients with more severe conditions (patients with acute hepatitis, fulminant hepatitis, and hepatocellular carcinoma and patients undergoing post-liver transplantation), the utilities of these severe conditions were estimated by three hepatitis experts using the EQ-5D-5L. The means of the utilities for acute hepatitis, fulminant hepatitis, asymptomatic chronic hepatitis, chronic hepatitis, compensated cirrhosis, compensated cirrhosis, hepatocellular carcinoma stage I/II, hepatocellular carcinoma stage III/IV, and post-liver transplantation were 0.529, - 0.111, 0.904, 0.868, 0.845, 0.722, 0,675, 0,428, and 0.651 and 0.876, 0.821, 0.737, 0.671, 0.675, 0.428, and 0.651 in HB and HC, respectively. To the best of our knowledge, this is the first study that comprehensively assessed the health state utilities of patients with HB, HC and hepatitis-related conditions from a nationwide survey in Japan using the EQ-5D-5L.
Topics: Carcinoma, Hepatocellular; Health Status; Hepatitis A; Hepatitis B; Hepatitis C; Humans; Japan; Liver Cirrhosis; Liver Neoplasms; Massive Hepatic Necrosis; Quality of Life; Surveys and Questionnaires
PubMed: 36229479
DOI: 10.1038/s41598-022-21470-3