Predictors of mortality in patients with yellow fever: an observational cohort study

Kallas, Esper G.; Zanella, Luiz Gonzaga Francisco de Assis Barros D’Elia; Moreira, Carlos Henrique Valente; Buccheri, Renata; Diniz, Gabriela Bezerra Freitas; Castiñeiras, Anna Carla Pinto; Costa, Priscilla R.; Dias, Juliana Zanatta de Carvalho; Marmorato, Mariana Prado; Song, Alice; Maestri, Alvino; Borges, Igor C.; Joelsons, Daniel; Cerqueira, Natalia B; Souza, Nathália Caroline Santiago e; Claro, Ingra Morales; Sabino, Éster Cerdeira; Levi, José Eduardo; Avelino‐Silva, Vivian Iida; Ho, Yeh‐Li

doi:10.1016/s1473-3099(19)30125-2

Cited by 75 publications

(101 citation statements)

References 33 publications

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“…A correlation between viral load and worse outcome has been reported in nonhuman primates infected with YFV ( 47 ) as well as in patients with YFV, ( 5 ) and this relationship was recapitulated in our mouse model. Therefore, even though our findings suggest that de novo expression of ITPR3 in hepatocytes may be an endogenous protective mechanism in YFV infection, there also may be limits to the extent of this beneficial effect.…”

Section: Discussionsupporting

confidence: 77%

“…The current findings complement and extend other recent clinical observations of YF liver failure, including the presence of massive hepatocellular necrosis and microvesicular steatosis, plus the rapid progression of coagulopathy, encephalopathy, and acute kidney injury. ( 5‐7,37 ) Hepatocytes of infected patients also began to heavily express ITPR3, a calcium channel that is normally absent or minimally expressed in hepatocytes. ( 19,20,38 ) This change was observed in a mouse model of YFV infection as well.…”

Section: Discussionmentioning

confidence: 99%

“…( 4 ) The infection was fatal in more than one‐third of these patients, and the lethal cases were mostly attributed to acute liver failure. ( 5 ) Therefore, YF remains a major health problem despite intense study about transmission and prophylaxis of the virus and the availability of an effective vaccine. The pathogenesis of the liver disease caused by YFV is poorly understood; indeed, treatment of infected individuals has typically been limited to supportive measures.…”

mentioning

confidence: 99%

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Molecular Mechanism for Protection Against Liver Failure in Human Yellow Fever Infection

Lemos¹,

França²,

Filho³

et al. 2020

Hepatol Commun

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Yellow fever (YF) is a viral hemorrhagic fever that typically involves the liver. Brazil recently experienced its largest recorded YF outbreak, and the disease was fatal in more than a third of affected individuals, mostly because of acute liver failure. Affected individuals are generally treated only supportively, but during the recent Brazilian outbreak, selected patients were treated with liver transplant. We took advantage of this clinical experience to better characterize the clinical and pathological features of YF‐induced liver failure and to examine the mechanism of hepatocellular injury in YF, to identify targets that would be amenable to therapeutic intervention in preventing progression to liver failure and death. Patients with YF liver failure rapidly developed massive transaminase elevations, with jaundice, coagulopathy, thrombocytopenia, and usually hepatic encephalopathy, along with pathological findings that included microvesicular steatosis and lytic necrosis. Hepatocytes began to express the type 3 isoform of the inositol trisphosphate receptor (ITPR3), an intracellular calcium (Ca2+) channel that is not normally expressed in hepatocytes. Experiments in an animal model, isolated hepatocytes, and liver‐derived cell lines showed that this new expression of ITPR3 was associated with increased nuclear Ca2+ signaling and hepatocyte proliferation, and reduced steatosis and cell death induced by the YF virus. Conclusion: Yellow fever often induces liver failure characterized by massive hepatocellular damage plus steatosis. New expression of ITPR3 also occurs in YF‐infected hepatocytes, which may represent an endogenous protective mechanism that could suggest approaches to treat affected individuals before they progress to liver failure, thereby decreasing the mortality of this disease in a way that does not rely on the costly and limited resource of liver transplantation.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Molecular Mechanism for Protection Against Liver Failure in Human Yellow Fever Infection

Lemos¹,

França²,

Filho³

et al. 2020

Hepatol Commun

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“…Upon diagnosis, the clinician may be able to identify patients with risk factors for developing more severe yellow fever, such as those patients with older age, or presenting with high AST levels 6 and high neutrophil counts and YF viral load. 7 In the work by Kallas et al, higher levels of creatinine and bilirubin, as well as coagulopathy, were associated with higher mortality in the univariate analyses but were interestingly not independent predictors of death as determined by multivariate analyses. 7 Ho's paper narrows down on those with more severe clinical presentation as it describes the clinical outcomes for those patients admitted to the Intensive Care Unit (ICU).…”

mentioning

confidence: 89%

Improving clinical management of patients with severe yellow fever

Wilder‐Smith

Chen

Melo

et al. 2019

The Lancet Infectious Diseases

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“…Dr. Esper Kallas (University of Sao Paulo, Brazil) presented data obtained using a cohort from the recent YFV infection outbreak that occurred in the perimeter of São Paulo city in 2018. A direct correlation between YFV loads and increased chances of death was found when associated with increased neutrophil numbers, alanine and aspartate transaminases, international normalized ratio, creatinine, and bilirubin levels [57]. To fully recover, the patient requires long-term intensive hospital support, and sometimes even a liver transplant [58].…”

Section: Yellow Fevermentioning

confidence: 99%