Materiały źródłowe

• #1 Hepatitis A | AAFP

  https://www.aafp.org/pubs/afp/issues/2006/0615/p2162.html

  Hepatitis A is caused by a nonenveloped RNA picornavirus that infects only primates. Lack of a lipid envelope confers resistance to bile lysis. The virus is hardy, surviving on human hands and fomites and requiring temperatures higher than 185F (85C) for inactivation. Hepatitis A virus survives for extended periods in seawater, fresh water, wastewater, and soil. The virus is resistant to freezing, detergents, and acids, but it is inactivated by formalin and chlorine. […] Infection occurs primarily by oral inoculation of fecally excreted virus either by person-to-person contact (including any form of sexual contact with proximity to feces) or by ingestion of contaminated food or water. Viral particles are replicated only in hepatocytes and gastrointestinal epithelial cells and are released into blood and bile by a mechanism that does not cause cell lysis. Liver cells are destroyed by a cell-mediated immune response.

• #2 Hepatitis A | The Australian Immunisation Handbook

  https://immunisationhandbook.health.gov.au/contents/vaccine-preventable-diseases/hepatitis-a

  Hepatitis A is an acute viral infection of the liver, which can cause mild to severe illness. The illness is usually self-limiting and needs no treatment. It is transmitted primarily by the faecal–oral route by ingesting contaminated food and water, or by direct contact with an infectious person. Hepatitis A is highly contagious. […] The incubation period is 15–50 days, with a mean of about 28 days. Infected people excrete HAV in faeces for: up to 2 weeks before the onset of illness, at least 1 week after the illness. HAV does not cause chronic infection. Immunity after infection is lifelong. […] Hepatitis A is a human infection. There is no animal reservoir. HAV is mainly transmitted by the faecal–oral route, primarily by ingesting contaminated food or water. The infecting dose is unknown, but is probably low. […] HAV survives well in the environment outside the human host. It persists on hands for several hours and in food kept at room temperature for much longer. It is also relatively resistant to heat and freezing.

• #3 Hepatitis A pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Hepatitis_A_pathophysiology

  Peak infectivity occurs during the 2-week period before onset of jaundice, or elevation of liver enzymes, when the concentration of virus in stool is highest. […] The concentration of virus in stool declines after jaundice appears. […] Most infected persons no longer excrete virus in the feces by the third week of illness. […] Children may excrete virus longer than adults. […] Chronic shedding of HAV in feces does not occur; however, shedding can occur in persons who have relapsing illness. […] The virus is resistant to detergent, acid, solvents, drying, and temperatures up to 60C. It can survive for months in salt water. Common-source outbreaks, such as water or restaurants are typical. […] HAV can be inactivated by chlorine treatment, formalin, peracetic acid, beta-propiolactone, and UV radiation.

• #4

  https://www.who.int/news-room/fact-sheets/detail/hepatitis-a

  Hepatitis A is an inflammation of the liver caused by the hepatitis A virus (HAV). The virus is primarily spread when an uninfected (and unvaccinated) person ingests food or water that is contaminated with the faeces of an infected person. […] Unlike hepatitis B and C, hepatitis A does not cause chronic liver disease but it can cause mild to severe symptoms and rarely fulminant hepatitis (acute liver failure), which is often fatal. […] Hepatitis A viruses persist in the environment and can withstand food production processes routinely used to inactivate or control bacterial pathogens. […] The hepatitis A virus is transmitted primarily by the faecal-oral route; that is when an uninfected person ingests food or water that has been contaminated with the faeces of an infected person. […] The virus can also be transmitted through close physical contact (such as oral-anal sex) with an infectious person, although casual contact among people does not spread the virus.

• #5 Hepatitis A | AAFP

  https://www.aafp.org/pubs/afp/issues/2021/1000/p368.html

  Hepatitis A virus is a nonenveloped positive-strand RNA virus classified as a picornavirus, whose only natural host is humans. Remarkably stable in many environments and able to survive on surfaces for weeks, hepatitis A virus is transmitted through ingestion of infected stool particles. The virus is absorbed in the stomach and intestines, travels to the liver via the portal circulation, and replicates in hepatocytes. Detectable virus appears in blood and feces approximately 10 to 12 days after infection and may be excreted in stool for up to three weeks after the onset of symptoms. Viral shedding may begin weeks before symptom onset, contributing to the scope of outbreaks. […] Patients with hepatitis A are most likely to spread the disease in the 14 days before jaundice develops, corresponding with the highest level of the virus in the stool. Infectivity decreases after jaundice is observed, and most individuals are considered to be noninfectious one week after the onset of jaundice.

• #6 Pathogenesis and Diagnosis of Hepatitis A Virus and Other Biodefense Agents | FDA

  https://www.fda.gov/vaccines-blood-biologics/science-research-biologics/pathogenesis-and-diagnosis-hepatitis-virus-and-other-biodefense-agents

  Hepatitis A virus (HAV) causes acute hepatitis in humans, and as a potential agent of bioterrorism (BT) it poses a threat to the safety of the blood supply. […] Since the biology of HAV is poorly understood, we study the role of the hepatitis A virus receptor 1 in pathogenesis of HAV in animal models. […] HAVCR1 (CD365) and its mouse ortholog are functional hepatitis A virus (HAV) cellular receptors that mediate HAV infection.

• #7 Hepatitis A virus (HAV): properties, classification, mode of transmission, pathogenesis, clinical features and laboratory diagnosis – Online Biology Notes

  https://www.onlinebiologynotes.com/hepatitis-a-virus-hav-properties-classification-mode-of-transmission-pathogenesis-clinical-features-and-laboratory-diagnosis/

  Human is the primary reservoir of Hepatitis A virus. The virus may survive outside the body for months. […] HAV infection is caused by ingestion of contaminated foods or water. The virus first multiplies in the intestinal epithelium and then enter the blood stream and then migrates to liver parenchymal cells. […] HAV attaches to liver cell through Ig-like cellular receptor on the host cell and enter inside the cell by receptor mediated endocytosis. […] Inside the endosome, virus releases VPg protein which creates pores on the endosomal membrane and releases viral genome in the hosts cytoplasm and damage the hepatocytes. […] Virus multiplication occurs in hepatocytes and Kupffers cells causing monuclear infiltrate, ballooning of hepatocytes, degeneration and acidophilic bodies in the hepatocytes.

• #8 Chapter 9: Hepatitis A | Pink Book | CDC

  https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-9-hepatitis-a.html?CDC_AAref_Val=https://www.cdc.gov/vaccines/pubs/pinkbook/hepa.html

  HAV is typically acquired through ingestion (through fecal-oral transmission) and replicates in the liver. […] After 10 to 12 days, virus is present in blood and is excreted via the biliary system into the feces. […] Peak titers occur during the 2 weeks before onset of illness. […] Although virus is present in serum, its concentration is several orders of magnitude less than in feces. […] Virus excretion begins to decline at the onset of clinical illness and decreases significantly by 7 to 10 days after onset of symptoms. […] Most infected persons no longer excrete virus in the feces by the third week of illness.

• #9 Hepatitis A pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Hepatitis_A_pathophysiology

  Hepatitis A is a liver disease caused by the hepatitis A virus (HAV). HAV has fecal-oral transmission and its infectivity peaks about 2-weeks before the onset of jaundice. Gross observation of the liver may show an enlarged and erythematous liver, while microscopically it may reveal lymphocyte infiltration and inflammation of the portal tracts. […] Hepatitis A is a liver disease caused by the HAV that can affect anyone. […] HAV is acquired by mouth (through fecal-oral transmission) and replicates in the liver. After 10-12 days, the virus is present in blood and is excreted via the biliary system into the feces. […] Peak titers occur during the 2 weeks before onset of illness. Although virus is present in serum, its concentration is several orders of magnitude less than in feces. Virus excretion begins to decline at the onset of clinical illness, and has decreased significantly by 710 days after onset of symptoms.

• #10 Natural History, Clinical Manifestations, and Pathogenesis of Hepatitis A

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6120688/

  Hepatitis A virus (HAV) is transmitted by the fecaloral route and is a major cause of acute viral hepatitis. […] Liver injury during hepatitis A is not directly caused by HAV but is known to be caused by immune-mediated mechanisms. […] In addition, mechanisms of immunopathogenesis in hepatitis A are discussed. […] The mechanism for liver injury during hepatitis A has not yet been clearly elucidated. […] However, it is known that the liver injury is not caused by direct cytopathic effect of HAV. […] Instead, liver injury in hepatitis A is caused by immune-mediated mechanisms involving both innate and adaptive immune responses to the virus. […] During hepatitis A, the appearance of T cells in the liver temporally coincides with an increase in serum ALT levels, suggesting an important role for T cells in liver injury.

• #11 Hepatitis A: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/177484-overview

  HAV is a single-stranded, positive-sense, linear RNA enterovirus of the Picornaviridae family. In humans, viral replication depends on hepatocyte uptake and synthesis, and assembly occurs primarily in the liver cells. Virus acquisition results almost exclusively from ingestion (eg, fecal-oral transmission), although isolated cases of parenteral transmission have been reported. […] Hepatocyte uptake involves a receptor, identified by Kaplan et al, on the plasma membrane of the cell, and viral replication is believed to occur exclusively in the hepatocytes. […] Many authorities believe that hepatocyte injury is secondary to the host’s immunologic response. This hypothesis is supported by the lack of cytotoxic activity in tissue culture and correlations between immunologic response and the manifestations of hepatocyte injury.

• #12 Natural History, Clinical Manifestations, and Pathogenesis of Hepatitis A

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6120688/

  Virus-specific CD8+ T cells may contribute to both viral control and liver injury in HAV-infected hosts. […] A role for natural killer T (NKT) cells was suggested in relation to the 157insMTTTVP polymorphism described above in the gene encoding TIM-1/HAVCR1. […] Early clinical studies showed immune complex deposition in the liver and reduced levels of serum complement in hepatitis A patients. […] Diverse cytokines and chemokines play a role in immune-mediated host injury by their effector and immunomodulatory functions. […] In hepatitis A patients, serum levels of several cytokines and chemokines are increased compared with healthy controls, including interleukin (IL)-6, IL-8, IL-18, IL-22, CXC-chemokine ligand (CXCL)9, and CXCL10. […] In summary, how T cells contribute to liver injury in hepatitis A has yet to be fully elucidated, including antigen specificity, subsets, activating signals, and effector molecules, all of which need to be further clarified.

• #13 Transmission Mechanism on Hepatitis A Virus (HAV)

  https://www.longdom.org/open-access/transmission-mechanism-on-hepatitis-a-virus-hav-99134.html

  Infection with hepatitis A virus (HAV) is a prevalent cause of acute viral hepatitis all over the world. The pathogenic mechanisms of hepatitis A are still unknown despite decades of investigation. […] However, evidence is mounting suggesting Natural Killer (NK) cells, Natural Killer T (NKT) cells, and even non-HAV-specific CD8+ T cells play a role in liver damage during HAV infection. […] The present state of knowledge about the mechanisms of hepatocellular damage in hepatitis A is summarized in this paper. […] HAV enters the bloodstream by a poorly understood pathway after fecaloral transfer to acquire access to the liver, the target organ, for growth. […] HAV usurps the cellular endosomal sorting complex to exit as membrane-cloaked, quasi-enveloped particles (eHAV), which provides a long-sought explanation for HAV’s noncytolytic discharge and dissemination.

• #14 Hepatitis A virus infection in adults: Epidemiology, clinical manifestations, and diagnosis – UpToDate

  https://www.uptodate.com/contents/hepatitis-a-virus-infection-in-adults-epidemiology-clinical-manifestations-and-diagnosis

  Hepatic injury occurs as a result of the host immune response to HAV. Viral replication occurs in the hepatocyte cytoplasm; hepatocellular damage and destruction of infected hepatocytes is mediated by human leukocyte antigen-restricted, HAV-specific CD8+ T lymphocytes and natural killer cells. Interferon-gamma appears to have a central role in promoting clearance of infected hepatocytes. An excessive host response (denoted by a marked reduction of circulation HAV ribonucleic acid (RNA) during acute infection) is associated with severe hepatitis.

• #15 Hepatitis A | Cleveland Clinic

  https://my.clevelandclinic.org/departments/digestive/medical-professionals/hepatology/hepatitis-a

  Hepatitis A virus (HAV) is a cause of acute liver inflammation or hepatitis. […] The virus is a 27-nm-diameter nonenveloped RNA virus. […] Viral replication and assembly occur in the hepatocyte cytoplasm of humans and nonhuman primates, the virus exclusive natural hosts. […] HAV is not directly cytopathic to the hepatocyte. Injury to the liver is secondary to the host’s immune response. Replication of HAV occurs exclusively within the cytoplasm of the hepatocyte. Human leukocyte antigen (HLA)-restricted, HAV-specific CD8+ T lymphocytes and natural killer cells mediate hepatocellular damage and destruction of infected hepatocytes. Interferon gamma appears to have a central role in promoting the clearance of infected hepatocytes.

• #16 Overview of hepatitis A virus infection in children – UpToDate

  https://www.uptodate.com/contents/overview-of-hepatitis-a-virus-infection-in-children

  The degree of hepatic injury during HAV infection depends upon the host’s immune response. HAV infection traditionally has been considered a biphasic process. In the first phase, a noncytopathic stage, viral replication occurs exclusively within the cytoplasm of the hepatocyte. During this first phase, HAV is released into the bile in the absence of elevation of the liver enzymes. Therefore, fecal shedding of HAV starts before the elevation of alanine aminotransferase (ALT). This phase is followed by a second phase, a cytopathic stage, with florid portal zone infiltration, necrosis, and erosion of the limiting plate and elevated ALT. Hepatocellular damage and destruction is not the result of a direct cytopathic effect by HAV but a process mediated by human leukocyte antigen (HLA)-restricted, HAV-specific CD8 lymphocytes and natural killer cells. Interferon gamma appears to have a central role in promoting clearance of infected hepatocytes. An excessive host response, reflected by a marked reduction in HAV RNA during acute infection, is associated with severe hepatitis and a possible fulminant course.

• #17 Hepatitis A pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Hepatitis_A_pathophysiology

  Virus-induced cytopathology may not be responsible for the pathologic changes seen in HAV infection, as liver disease may result primarily from immune mechanisms. Antigen-specific T-lymphocytes are responsible for the destruction of infected hepatocytes. […] Common histologic findings include: Inflammatory infiltrates (lymphocytes), Necrosis and apoptosis of hepatocytes, The hepatocyte inflammation may have the following patterns: Multifocal, Panacinar, Inflammation of portal tracts. […] Confluent hepatic necrosis may lead to fulminant hepatitis and death in 30-60% of cases. Death appears to be inevitable when necrosis involves more than 65-80% of the total hepatocyte fraction. In patients who survive an episode of acute fulminant hepatic failure, neither functional nor pathologic sequelae are common, despite the widespread necrosis. […] During the recovery stage, cell regeneration is prominent. The damaged hepatic tissue is usually restored within 8 to 12 weeks.

• #18 Hepatitis A Virus- An Overview

  https://microbenotes.com/hepatitis-a-virus/

  Viral replication occurs primarily within hepatocytes and the secretion of virus into bile results in large quantities of virus being shed in the faeces. […] During the incubation period, viremia is observed at about the same time that fecal shedding of HAV is occurring. […] Viremia terminates shortly after hepatitis develops, whereas feces may remain infectious for another 1 to 2 weeks. […] Acute hepatitis includes features like inflammatory cell infiltration, hepatocellualr necrosis and liver cell regeneration. […] Portal infiltration by lymphocytes, plasma cells and periodic acid Schiff (PAS)-positive macrophages are prominent features in early biopsies. […] Parenchymal cells undergo ballooning degeneration. […] These hepatocytes are swollen and have indistinct plasma membranes, enlarged nuclei, and a featureless cytoplasm, except for some cytoplasmic remnants condensed around the nuclei.

• #19 Hepatitis A Virus- An Overview

  https://microbenotes.com/hepatitis-a-virus/

  Disruption of bile canaliculi may lead to bile retention after liver cell enlargement or necrosis. […] In some cases, extension of the inflammatory infiltrate from the periportal region into the hepatic parenchyma with significant erosion of the limiting plate is seen. […] HAV replication in the liver triggers a substantial immune response, both humoral and cell mediated. […] CD8 +, cytotoxic T cells that are capable of lysing autologous HAV infected cells , but not of controlling uninfected cells, are present both in circulation and in the liver at the site of disease. […] These virus specific T cells also produce interferon gamma and other cytokines at the site of infection that may be responsible for much of liver injury. […] In addition to cell mediated immune response, there is vigorous antibody response to the virus during later stages of infection which are directed against conformational epitopes. […] Neutralizing antiviral antibodies play an important role in clearance of the virus. […] Serum antibody responses are first noted at onset of symptoms and include virus specific IgM as well as IgG and IgA.

• #20 Hepatitis A: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/177484-overview

  The presence of disease manifestations and the severity of symptoms after HAV infection directly correlate with the patient’s age. […] The single most important determinant of illness severity is age; increasing age is directly correlated with an increasing likelihood of adverse events (ie, morbidity and mortality).

• #21 Hepatitis A | AAFP

  https://www.aafp.org/pubs/afp/issues/2006/0615/p2162.html

  The presence and severity of symptoms with hepatitis A virus infection is related to the patients age. Approximately 70 percent of infected adults develop symptoms, including jaundice. In contrast, only 30 percent of children younger than six years of age develop symptoms, which usually are nonspecific and flu-like without jaundice. […] The 7,700 cases of hepatitis A reported to the Centers for Disease Control and Prevention (CDC) in 2003 met the case definition of an acute illness with discrete onset of symptoms, jaundice, or elevated serum transaminase levels, and a positive antihepatitis A virus immunoglobulin M (IgM) result. […] Less than 1 percent of patients experience a fulminant course of illness characterized by worsening jaundice and development of encephalopathy. Advanced age and comorbid conditions such as chronic liver disease increase the risk of a fulminant course, which often results in death or an emergent liver transplant.

• #22 Pathogenicity and virulence of hepatitis A virus

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8043188/

  Hepatitis A is an acute infection of the liver, which is mostly asymptomatic in children and increases the severity with age. […] However, virus traits potentially modulating its virulence have been described and will be the focus of this revision. […] The underlying reasons associated to these different outcomes are still not fully understood and are likely related to host factors such as the underlying hepatic diseases and age, and/or to an excessive host immune response. […] The very special genome composition of HAV is also revealed in its very low GC and GC3 contents, 37% and 26%, respectively, vs the theoretical 50%. […] The low CpG content may contribute to avoid the induction of antiviral responses, and it has been described that HAV elicits a very limited type I IFN response.

• #23 Pathogenicity and virulence of hepatitis A virus

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8043188/

  The combination of a slow replication and a limited antiviral response results in low virulence. […] The IRES activity may presumably act as a virulence factor, and it is tempting to speculate that the ability to interact with the biogenesis of the pseudo-enveloped particles may also be a determinant of pathogenesis.

• #24 Hepatitis A virus infection associated with bilateral pleural effusion, ascites, and acalculous cholecystitis in childhood: a case report | Journal of Medical Case Reports | Full Text

  https://jmedicalcasereports.biomedcentral.com/articles/10.1186/s13256-024-04627-8

  Acute hepatitis A infection is common among children in developing nations. Rarely, it can be associated with extrahepatic complications such as pleural effusion, acalculous cholecystitis, and ascites. […] Hepatitis A infections presented with extrahepatic manifestations like pleural effusion, acalculous cholecystitis, and ascites are very rare, especially in children. […] HAV infection-induced acute hepatitis typically follows a benign, self-limiting course. […] Acute hepatitis caused by HAV infection may also present with rare extrahepatic manifestations, such as urticarial and maculopapular rash, acute kidney injury, autoimmune hemolytic anemia, aplastic anemia, acute pancreatitis, reactive arthritis, Guillain-Barre syndrome, pleural or pericardial effusion, ascites, glomerulonephritis, polyarteritis nodosa, thrombocytopenia, and cryoglobulinemia.

• #25 Hepatitis A virus infection associated with bilateral pleural effusion, ascites, and acalculous cholecystitis in childhood: a case report | Journal of Medical Case Reports | Full Text

  https://jmedicalcasereports.biomedcentral.com/articles/10.1186/s13256-024-04627-8

  In childhood, pleural effusion, ascites, and acalculous cholecystitis are rare manifestations due to hepatitis A virus infection. […] The exact mechanism of the effusion in hepatitis A virus infection is unknown; it appears to be multifactorial, potentially involving immune complex deposition or a direct viral invasion of the pleura. […] The association between hepatitis A and ascites has rarely been reported in both children and adults, with most cases documented in children at advanced disease stages. […] Acalculous cholecystitis is a rare complication of acute viral hepatitis A. […] This case highlights the significance of recognizing extrahepatic manifestations of childhood hepatitis A in primary care settings. […] Although HAV infection is an asymptomatic and self-limiting viral disease in childhood, it can manifest with rare extrahepatic complications.

• #26 Hepatitis A. An uncommon associated pathology | Allergologia et Immunopathologia

  https://www.elsevier.es/en-revista-allergologia-et-immunopathologia-105-articulo-hepatitis-a-an-uncommon-associated-S0301054610000546

  Our diagnosis was: Hepatitis A, Pleural Effusion, Thrombopenia, Hypoproteinaemia and Coagulopathy. […] Pleural effusion has been described as a rare extra-hepatic complication of acute viral hepatitis, but it is considered to be a rarer complication in the case of hepatitis A. […] The mechanism through which it occurs is unknown but it does not seem to be correlated to clinical evolution or to a worse prognosis of the disease; some authors defend autoimmune etiology (mediated by immunocomplexes), other authors defend parainflammatory etiology (as a result of liver inflammation). […] Thrombopenia has been described in relation to some types of hepatitis, especially hepatitis B and C, however it is uncommon in hepatitis A; its evolution is benign and self-limited. A peripheral platelet destruction is proposed to explain it, since normal megakaryocytes have been found in bone marrow; this destruction can be explained by an autoimmune mechanism (by circulating immunocomplexes, antiplatelet antibodies or by the development of antiphospholipid or transient anticardiolipin antibodies).

• #27

  https://www.ncbi.ncbi.grantome.com/grant/NIH/ZIA-AI000915-11

  Interestingly, innate immune responses were abbreviated in the latter chimpanzees, but detection of the innate immune response was almost as sensitive a diagnostic test of infection as was detection of specific serologic or molecular probes of HAV infection. […] The adaptive immune responses were also present, but not as robust as the adaptive immune responses in HCV infections of chimpanzees. […] This information will be useful for a better understanding of the pathogenesis of viral hepatitis.

• #28 Hepatitis A. An uncommon associated pathology | Allergologia et Immunopathologia

  https://www.elsevier.es/en-revista-allergologia-et-immunopathologia-105-articulo-hepatitis-a-an-uncommon-associated-S0301054610000546

  In conclusion, it is very likely that in developed countries the clinical pattern of hepatitis A undergoes important changes, because when the age of presentation increases due to the improvement of the healthcare conditions, the risk of suffering from complications increases. […] In this case, it is believed that the complications are due to autoimmune mechanisms, because of the rise of the antiphospholipid and anticardiolipin antibodies in the acute stage. […] Hepatitis A is usually a benign and self-limited disease, but special attention must be paid to its complications when they occur.

• #29 Transmission Mechanism on Hepatitis A Virus (HAV)

  https://www.longdom.org/open-access/transmission-mechanism-on-hepatitis-a-virus-hav-99134.html

  The mechanisms of hepatitis A-related liver damage are still unknown. […] Other immune cells that have been linked to liver injury include non-HAV-specific CD8+ T cells, NK cells, and NKT cells. […] Hepatitis A severity can also be influenced by genetic variations in both the host and viral variables. […] Further understanding of these pathways of HAV-induced hepatic injury will throw fresh insight on the pathophysiology of hepatitis A and aid in the development of new therapeutics.

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