Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism by which the virus associated with dengue fever can cause a fatal hepatitis is not well understood. The purpose of this study was to examine 9 cases of fatal dengue hemorrhagic fever-associated hepatitis, and to correlate the histologic findings with viral detection and cytokine response. The histologic changes were nonspecific and included massive hepatic necrosis and a pauci-cellular acute hepatitis. Viral cDNA detection by reverse transcriptase in situ polymerase chain reaction demonstrated that the fatal hepatitis was due to infection on average of >90% of hepatocytes and many Kupffer cells. Similar results were obtained using immunohistochemistry for viral protein using an automated highly sensitive system. Immunohistochemical analysis for tumor necrosis factor alpha, and interleukin-2, showed rare positive Kupffer cells. In comparison, fatal cases of hepatitis C associated liver failure demonstrated far fewer infected hepatocytes and a concomitant strong up-regulation of many cytokines, notably tumor necrosis factor alpha and interleukin-2. It is concluded that fatal dengue hemorrhagic fever is associated with acute, severe liver damage due primarily to massive direct infection of hepatocytes and Kupffer cells with minimal cytokine response. The infection can be readily detected in a few hours using an automated system that has a sensitivity equivalent to reverse transcriptase in situ polymerase chain reaction.
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PMID:Histologic, viral, and molecular correlates of dengue fever infection of the liver using highly sensitive immunohistochemistry. 1712 50

Dengue virus is estimated to cause over 100 million infections throughout the world annually. While dengue infections can have a wide range of infections, atypical manifestations have been described. These involve the central nervous system, cardiac alterations and hepatitis. Here, we highlight a case of dengue haemorrhagic fever (DHF) with fulminant hepatitis. A 55-year-old male was admitted for 16 days, developing severe thrombocytopenia as low as 6x10(9)/L, haematocrit of 48% with transaminitis: ALT: 3,515 U/L, AST: 12,541 U/L, GGT: 1,094 U/L. Subsequent investigations excluded any occult liver lesions, hepatitis A, B and C, Wilson's disease, Epstein-Barr virus and Cytomegalo virus as possible causes. His dengue PCR was positive. His condition subsequently improved with supportive treatment. Liver injury from dengue virus is mediated by its direct infection of hepatocytes and kupffer cells. While mild to moderate elevations of serum aminotransferases (ALT and AST<5X normal) are common in dengue virus infection, liver failure rarely dominate the clinical picture. Liver dysfunction was commoner in DHF, with case reports indicating that severe hepatic dysfunction (ALT and AST>10X normal) was seen with DHF associated with spontaneous bleeding tendencies. Overall prognosis depends on age and other concomitant co-morbidities. We seek to review the literature on dengue infections with hepatitis and discuss issues pertaining to pathophysiology of liver impairment in dengue, the frequency of transaminitis associated with DHF and the overall prognosis.
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PMID:Fulminant hepatitis in dengue haemorrhagic fever. 1730 19

Flaviviruses are major arthropod-borne human pathogens responsible for life-threatening encephalitis, hepatitis and haemorrhagic fevers. These enveloped, single-stranded, positive-sense RNA viruses encode a polyprotein precursor of about 3400 amino acids, processed into three structural and seven non-structural proteins. The non-structural glycoprotein NS1 is essential for flavivirus viability. During host-cell infection in vitro, NS1 is found associated with intracellular organelles as a requisite for its role in viral replication, or is transported to the cell surface where it may trigger specific signalling pathways. In addition, a secreted form of the protein is released from flavivirus-infected mammalian cells. We have previously shown that the NS1 protein circulates during the acute phase of the disease in the plasma of patients infected with dengue virus type 1 and have extended our retrospective studies to dengue type 2 and type 3 cohorts, confirming the value of the NS1 antigen as an alternative diagnostic marker. Interestingly, detection of the NS1 protein in yellow fever virus and West Nile virus infections suggests that NS1 secretion is a hallmark of human flavivirus infections. The objectives of our current studies are to define the biological properties of the secreted form of the NS1 protein, to evaluate its possible contribution to viral pathogenesis, and to validate this protein as a candidate target for passive immunoprophylaxis against flaviviruses.
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PMID:Secretion of flaviviral non-structural protein NS1: from diagnosis to pathogenesis. 1731 66

With the overall increase in international travel, there is likely to be an increase in travel during pregnancy as well. In developing countries, pregnant women face exposures that can add significant risk for neonatal morbidity and mortality. Infections that can occur in utero or in the early neonatal period include malaria, yellow fever, tuberculosis, hepatitis, human immunodeficiency virus, leishmaniasis, toxoplasmosis, filariasis, Japanese encephalitis, rubella, typhoid fever, leptospirosis, dengue fever, Helicobacter pylori, and trypanosomiasis. When travel and potential exposure cannot be avoided, preventive measures are usually effective. Pretravel consultation should include careful discussion of length of travel, antimalarial prophylaxis, insect avoidance, food and water hygiene, vaccination, and body fluid precautions.
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PMID:Congenital infections associated with international travel during pregnancy. 1736 82

As the spread of dengue and dengue haemorrhagic fever is increasing, atypical manifestations are also on the rise, although they may be under reported because of lack of awareness. This review compiles descriptions of atypical manifestations of dengue, such as dengue encephalitis, dengue myocarditis, dengue hepatitis and dengue cholecystitis.
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PMID:Atypical manifestations of dengue. 1787 19

Yellow fever (YF) is a life-threatening mosquito-borne flaviviral hemorrhagic fever (VHF) characterized by severe hepatitis, renal failure, hemorrhage, and rapid terminal events with shock and multi-organ failure. A live, attenuated vaccine (YF 17D), in wide use for over 60 years, causes a disease identical to wild-type virus at an incidence of 2.5x10(-6). Our current understanding of the pathogenesis and treatment of YF (described in this brief review) is derived from studies of animal models (macaques, hamsters) that reproduce the features of human YF and from descriptive studies of human cases of naturally acquired and vaccine-associated VHF. The least understood, but potentially most important terminal events appear to be due to 'cytokine storm' and represent a potential target for therapeutic interventions. Areas for future study include dissection of cytokine-mediated events in animal models, the pathogenic role of the profound neutrophilia that occurs pre-terminally, the (pathological) role of adaptive immune clearance in pathogenesis, and treatments directed at cytokine storm. Antibody, interferon-alpha, polyICLC and other immune modulators are highly effective when administered before or within a narrow time window after infection, but are ineffective when given after the infection is established. A few antivirals have been evaluated (ribavirin, tiazofurin, carboxamide, pyrazoline compounds). Ribavirin has been used successfully to treat hamsters when the drug is given at high doses up to 2 days after virus infection (shortly before liver infection), but has not shown promise in nonhuman primate models. Future work should focus on evaluating higher doses of ribavirin alone or in combinations with potentially synergistic drugs, including interferons. Also specific inhibitors against other flaviviruses such as dengue virus should be investigated for potential pan-flavivirus activity since recent studies have shown that specific targets such as the flavivirus proteases and helicases are very similar in structure.
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PMID:Treatment of yellow fever. 1806 88

Acute hepatitis and hepatic encephalopathy are rare manifestations of dengue haemorrhagic fever (DHF). We report 4 children aged 8 months to 3 y who presented with severe hepatic dysfunction. Three male infants had in addition hepatic encephalopathy and 2 of them succumbed to their disease suggesting that hepatitis with encephalopathy has a very high mortality.
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PMID:Dengue and liver disease. 1860 99

Many infectious diseases are transmissible by blood transfusion but the overall risk of transfusion transmitted infections is very low through the combination of restrictive donor selection and increasingly sensitive screening. The noninfectious risks (hemolytic transfusion reactions, circulatory overload, transfusion related lung injury) are higher than the current infectious risks. Bacterial contamination of blood components remains the most frequent infectious risk from transfusion but are constantly declining. The estimated residual risk for transfusion transmitted HIV and hepatitis are lower 1/2 600 000 for HIV, 1/6 500 000 for HCV, 1/1 700 000 for HBV. For the future, the concerns are the risks of emerging or reemerging infections transmitted by blood as dengue, Chickungunya, West Nile Virus... Four transfusion transmissions of vCJD have been reported in UK, uncertainties about the incubation periods, the number of infected donors and the lack of sensitive assays for screening blood aggravate concerns about the transfusion transmission risks for vCJD. The ultimate strategy against infectious disease (all but vCJD) could be to develop inactivation methods. Pathogen inactivation have been implemented for plasma, are expected to become available for platelets, but for red blood cells are only in development.
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PMID:[Update on infectious risks associated with blood products]. 1925 89

One difficulty in studying dengue virus (DENV) is the lack of an experimental model that reproduces the human disease. In a previous work, we have shown that BALB/c mice intraperitoneally inoculated with a DENV-2 isolate presented viremia and mild focal areas of liver injuries. In this study, mice were inoculated by the intravenous route and presented extensive damage areas in the liver tissue, which were evaluated by histopathological and ultrastructural analysis. Hepatic injury was noted mainly around the central vein and portal tracts. Damages consist of hepatocyte injury, including steatosis, swelling and necrosis. Further, erythrophagocytosis, intercellular edema and vascular damages were evident, including hemorrhage, which is characteristic of the dengue-induced hepatitis in human liver. Hepatic lesions were already noted 2 days post infection (p.i.), although effects were more extensive after the seventh day p.i. An increase in alanine aminotransferase and aspartate aminotransferase serum levels was detected 7 and 14 days p.i., respectively, and had correlation to hepatic lesions. Alterations caused by the DENV infection were self-limiting, with a remarkable reduction of all liver damages 49 days p.i. Virus antigens were detected in hepatocytes, Kupffer cells and vascular endothelium, suggesting virus replication in these cells. In situ hybridization, using a probe that anneals in the virus negative RNA strand, showed positive reaction in hepatocytes and vascular endothelium cells of infected mice, thus confirming virus replication in such cells. In general, results revealed that this mouse model reproduces some histopathological effects observed in humans and supports previous findings indicating virus replication in the hepatic tissue.
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PMID:Hepatic damage associated with dengue-2 virus replication in liver cells of BALB/c mice. 1972 15

This is a retrospective study of the gastrointestinal symptoms, signs and laboratory parameters in adult dengue patients admitted to Kuala Lumpur Hospital from 1st December 2004 to 31st December 2004. Clinical and laboratory parameters that may predict the need for intensive care were investigated. Six hundred sixty-six patients with clinical and biochemical features consistent with dengue infection were identified. Patients were stratified into those who required intensive care and those who were managed in non high dependency wards. Serum alanine aminotransaminase (ALT) levels were normal in 22.8% of patients and 5.9% of patients had acute fulminant hepatitis. More patients with dengue haemorrhagic fever (DHF) had elevated ALT levels as compared to patients with classic dengue fever (DF) (p = 0.012). Patients with DF had a statistically significant lower mean ALT level as compared to patients with DHF. Abdominal pain (p = 0.01) and tenderness (p<0.001), gastrointestinal bleed (p<0.001), jaundice (p<0.001), hepatomegaly (p<0.001) and ascites (p<0.001) were predictors of need for intensive care. We conclude that gastrointestinal manifestations are very common in dengue patients. Presence of abdominal pain and tenderness, gastrointestinal bleed, jaundice, hepatomegaly and ascites can be used to triage patients requiring intensive care.
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PMID:Gastrointestinal manifestations of dengue infection in adults. 1980


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