Incidence and Clinical Outcome of Acute Liver Failure Caused by Dengue in a Hospital for Tropical Diseases, Thailand

Mon, Khin Kye; Nontprasert, Apichart; Kittitrakul, Chatporn; Tangkijvanich, Pisit; Leowattana, Wattana; Poovorawan, Kittiyod

doi:10.4269/ajtmh.16-0374

Cited by 44 publications

(37 citation statements)

References 25 publications

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“…The main purpose here was to identify whether these samples presented an environment which is consistent with a DAMP-mediated response. Based on the fact that the liver is one of the main organs affected by dengue 35 – 38 and that lungs and heart are also important sites involved with the severe disease 13 , 37 , 39 – 41 , samples from all these three organs were considered.…”

Section: Resultsmentioning

confidence: 99%

Dengue fatal cases present virus-specific HMGB1 response in peripheral organs

Oliveira

Póvoa

Nuovo

et al. 2017

Sci Rep

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Dengue is an important infectious disease that presents high incidence and yields a relevant number of fatal cases (about 20,000) every year worldwide. Despite its epidemiological relevance, there are many knowledge gaps concerning dengue pathogenesis, especially with regards to the circumstances that drive a mild clinical course to a severe disease. In this work, we investigated the participation of high mobility group box 1 (HMGB1), an important modulator of inflammation, in dengue fatal cases. Histopathological and ultrastructural analyses revealed that liver, lung and heart post-mortem samples were marked by tissue abnormalities, such as necrosis and apoptotic cell death. These observations go in line with an HMGB1-mediated response and raised concerns regarding the participation of this cytokine in promoting/perpetuating inflammation in severe dengue. Further experiments of immunohistochemistry (IHC) showed increased expression of cytoplasmic HMGB1 in dengue-extracted tissues when compared to non-dengue controls. Co-staining of DENV RNA and HMGB1 in the host cell cytoplasm, as found by in situ hybridization and IHC, confirmed the virus specific induction of the HMGB1-mediated response in these peripheral tissues. This report brings the first in-situ evidence of the participation of HMGB1 in severe dengue and highlights novel considerations in the development of dengue immunopathogenesis.

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Section: Resultsmentioning

confidence: 99%

Dengue fatal cases present virus-specific HMGB1 response in peripheral organs

Oliveira

Póvoa

Nuovo

et al. 2017

Sci Rep

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“…The three largest experiences, that studied liver involvement in patients with DF and included more than 3,500 patients, did not find any patient of ALF [ 7 11 18 ]. A recent large retrospective study of 1,926 patients revealed a low (0.31%) incidence rate of ALF in patients with DF [ 8 ]. Over representation of dengue related ALF in few series may be because of undiagnosed co-infection with hepatotropic viruses that could cause ALF or factors related to virulence of the virus involved in a given study.…”

Section: Discussionmentioning

confidence: 99%

“…Liver injury (LI) in patients with DENV infection is common and several hypotheses have been proposed to explain the mechanism of LI [ 5 ]. Severity of LI ranges from asymptomatic mild elevation of serum levels of aminotransferase to life-threatening acute liver failure (ALF) [ 6 7 8 ]. The majority of data on LI in DENV infection is from the adult population.…”

Section: Introductionmentioning

confidence: 99%

Validation of Serum Aminotransferases Levels to Define Severe Dengue Fever in Children

Srivastava

Chhavi

Goel

2018

Pediatr Gastroenterol Hepatol Nutr

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PurposeWe aimed to study the pattern of liver-injury in children with dengue fever (DF) and validate serum aminotransferase ≥1,000 IU/L as a marker of severe DF.MethodsChildren admitted with DF were included. DF was defined by presence of clinical criteria and positive serological or antigen tests in absence of other etiology. DF severity was graded as dengue without or with warning signs and severe dengue. Liver-injury was defined as alanine aminotransferase (ALT) more than twice the upper limit of normal (boys, 30 IU/L; girls, 21 IU/L).ResultsOf 372 children with DF, 144 (38.7%) had liver-injury. Risk of liver-injury and aminotransferase levels increased with DF severity (p<0.001). Recommended ALT and aspartate aminotransferase (AST) cut-off at ≥1,000 IU/L had sensitivity 4.8% (5/105), specificity 99.3% (265/267) for detection of severe DF. In children with ALT and AST <1,000 IU/L (n=365), the area under receiver operating curves for prediction for severe DF, were 0.651 (95% confidence interval [CI], 0.588–0.714; p<0.001) for ALT and 0.647 (95% CI, 0.582–0.712; p<0.001) for AST. Serum ALT at 376 IU/L and AST at 635 IU/L had sensitivity and specificity comparable to ≥1,000 IU/L for defining severe DF.ConclusionLiver-injury is common in DF. The ALT and AST levels increase with DF severity. ALT and AST levels of ≥1,000 IU/L could be lowered to 376 IU/L and 635 IU/L respectively for defining severe DF.

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“…In the December issue of the Journal, Kye Mon and others describe liver-related complications among 1,926 patients with serologically confirmed dengue infection in Thailand 1. Although the study found only six individuals with acute liver failure, it serves to emphasize how lethal this complication can be.…”

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confidence: 99%