Regular paracetamol in severe dengue: a lethal combination?

Gan, Chin Seng; Chong, Sze Yee; Lum, Lucy Chai See; Lee, Way Seah

doi:10.11622/smedj.2013037

Cited by 9 publications

(13 citation statements)

References 9 publications

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“…APAP is the most commonly used drug to treat dengue symptoms [ 6 ] and there are studies showing that dengue patients who use APAP are at increased risk of developing liver failure [ 14 ]. Many studies have evaluated the liver damage resulting from the association between DENV and APAP [ 6 , 15 , 36 , 37 ] but, despite evidence suggesting that this association may lead to severe hepatic insufficiency, no studies have yet been performed to evaluate cellular and molecular mechanisms involved in hepatocyte response to the association between DENV and APAP. Thus, this study evaluated the transcriptional changes in hepatocytes resulting from the association between DENV infection and APAP treatment and the possible effects of these changes on the molecular and cellular mechanisms that influence cellular homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Signatures in AML-12 Hepatocyte Cells upon Dengue virus Infection and Acetaminophen Treatment

Ferreira¹,

Gava²,

Oliveira

et al. 2020

Viruses

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Dengue is an acute viral disease caused by Dengue virus (DENV) and is considered to be the most common arbovirus worldwide. The clinical characteristics of dengue may vary from asymptomatic to severe complications and severe organ impairment, particularly affecting the liver. Dengue treatment is palliative with acetaminophen (APAP), usually known as Paracetamol, being the most used drug aiming to relieve the mild symptoms of dengue. APAP is a safe and effective drug but, like dengue, can trigger the development of liver disorders. Given this scenario, it is necessary to investigate the effects of combining these two factors on hepatocyte homeostasis. Therefore, this study aimed to evaluate the molecular changes in hepatocytes resulting from the association between DENV infection and treatment with sub-toxic APAP concentrations. Using an in vitro experimental model of DENV-2 infected hepatocytes (AML-12 cells) treated with APAP, we evaluated the influence of the virus and drug association on the transcriptome of these hepatocytes by RNA sequencing (RNAseq). The virus–drug association was able to induce changes in the gene expression profile of AML-12 cells and here we highlight and explore these changes and its putative influence on biological processes for cellular homeostasis.

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Section: Discussionmentioning

confidence: 99%

Gene Expression Signatures in AML-12 Hepatocyte Cells upon Dengue virus Infection and Acetaminophen Treatment

Ferreira¹,

Gava²,

Oliveira

et al. 2020

Viruses

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“…However, acetaminophen is available over-the-counter at no charge, extensively advertised in the lay media, and part of the therapeutic routine recommended by the Brazilian Ministry of Health 8 for self-treatment of dengue symptoms. Repeated acetaminophen use, even at therapeutic doses, may increase serum aminotransferase levels; inadvertent use of high doses may lead to severe liver injury and death [15][16][17] . Considering, the high frequency of hepatic impairment observed in this study, we advise that acetaminophen be used with caution in cases of DHF.…”

Section: Discussionmentioning

confidence: 99%

Predictive factors of dengue severity in hospitalized children and adolescents in Rio de Janeiro, Brazil

Ferreira

Kubelka

Velarde

et al. 2018

Rev. Soc. Bras. Med. Trop.

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Introduction: Dengue is one of the most important mosquito-borne infections. Severe cases are more frequently observed in adults. However, in 2008, the State of Rio de Janeiro, Brazil, experienced a severe dengue epidemic that primarily affected children and caused many cases of dengue hemorrhagic fever (DHF) and death. Methods: A cross-sectional analytical study was conducted to examine laboratory diagnosis and clinical epidemiologic factors for confirmed dengue cases in patients aged less than 16 years, from January to June 2008, at a municipal hospital in the City of Rio de Janeiro, Brazil. Variables associated with severe outcomes and P values less than .05 were evaluated by means of a logistic regression model. Results: Of the 419 dengue cases studied, 296 were classified as DHF and 123 as classical dengue. Six patients who had DHF died. In multivariate analysis, some laboratory and clinical variables were independently associated with DHF: age 5 years or older (odds ratio [OR], 4.94;

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“…The effects of potentially hepatotoxic drugs taken during the early stage of the disease on liver dysfunction are still controversial. 22,23 Because this study was retrospective, we could not collect data on the intake of acetaminophen or other hepatotoxic drugs in our studied population. Only five adults and three children received antibiotics, and no differences in liver dysfunction were observed.…”

Section: Discussionmentioning

confidence: 99%

Differences in Liver Impairment Between Adults and Children with Dengue Infection

Vega¹,

Phumratanaprapin²,

Phonrat³

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Dengue infection (DI) is a major vector-borne disease in southeast Asia and an important cause of morbidity. The complications such as hepatic impairment are common, and because the physiology of the liver differs between children and adults, the DI-associated liver impairments might be expected to differ as well. This study aims to compare the differences in liver impairment between adults and children with DI. We retrospectively studied 158 adults and 79 children with serologically confirmed DI admitted to the Bangkok Hospital for Tropical Diseases from 2008 to 2012. In total, 93% of adults and 87% of children exhibited abnormal liver enzyme levels during hospitalization. Overall, 76 (42.4%) adults and 16 (20.3%) children had dengue hemorrhagic fever (DHF). Compared with children, adults with dengue fever (DF) presented a significantly higher incidence of liver function impairment (alanine transaminase [ALT] > 2 × upper limit of normal [ULN]) (47.1% versus 25.5%), hepatitis (ALT > 4 × ULN) (29.4% versus 12.8%), and severe hepatitis (aspartate transaminase [AST]/ALT > 10 × ULN) (16.5% versus 4.3%). Children with DHF showed a significantly higher incidence of liver function impairment due to AST derangement than did adults (100% versus 73%). There were no differences in the total bilirubin, albumin, or total protein levels between adults and children. Liver enzymes normalized significantly more slowly in adults, and AST recovery was faster than ALT. In conclusion, liver function impairment was more common among adults than children with DF. As the severity progressed to DHF, liver injury became more common in children.

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Regular paracetamol in severe dengue: a lethal combination?

Cited by 9 publications

References 9 publications

Gene Expression Signatures in AML-12 Hepatocyte Cells upon Dengue virus Infection and Acetaminophen Treatment

Gene Expression Signatures in AML-12 Hepatocyte Cells upon Dengue virus Infection and Acetaminophen Treatment

Predictive factors of dengue severity in hospitalized children and adolescents in Rio de Janeiro, Brazil

Differences in Liver Impairment Between Adults and Children with Dengue Infection

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