During infection with the hepatitis A virus (HAV), most patients develop mild or asymptomatic disease. However, a small number of patients develop serious, life-threatening hepatitis. We investigated this variability in disease severity by examining 30 Argentinean patients with HAV-induced acute liver failure in a case-control, cross-sectional, observational study. We found that HAV-induced severe liver disease was associated with a 6-amino-acid insertion in TIM1/HAVCR1 (157insMTTTVP), the gene encoding the HAV receptor. This polymorphism was previously shown to be associated with protection against asthma and allergic diseases and with HIV progression. In binding assays, the TIM-1 protein containing the 157insMTTTVP insertion polymorphism bound HAV more efficiently. When expressed by human natural killer T (NKT) cells, this long form resulted in greater NKT cell cytolytic activity against HAV-infected liver cells, compared with the shorter TIM-1 protein without the polymorphism. To our knowledge, the 157insMTTTVP polymorphism in TIM1 is the first genetic susceptibility factor shown to predispose to HAV-induced acute liver failure. Furthermore, these results suggest that HAV infection has driven the natural selection of shorter forms of the TIM-1 protein, which binds HAV less efficiently, thereby protecting against severe HAV-induced disease, but which may predispose toward inflammation associated with asthma and allergy.
The clinical presentations were protean and not specific. A high index of suspicion is important for early diagnosis as it correlates with more benign lesions and more favorable outcume. The lower mortality rate in our series is concordant with that reported in more recent articles.
Hydatidosis is a parasitic infection caused by the Echinococcus granulosus larvae, transmitted by the ingestion of infected food, characterized by the formation of cysts in vital organs. In Argentina, the disease is spread throughout the territory, constituting an important public health issue. The disease usually affects the liver and lungs. The affection of other organs is rare, and even more uncommon the affection of the heart. We present the case of a disseminated hydatidosis in a pediatric patient, whose initial clinical manifestation was an acute arterial embolism of the right limb caused by the rupture of a hydatidic cardiac cyst.
Hepatitis A virus genotyping studies did not show any particularities, all cases were IA and, thus, apparent associations between genotype and the clinical presentation of acute liver failure could not be found.
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