Serial Evaluation of Children With ALF With Advanced MRI, Serum Proinflammatory Cytokines, Thiamine, and Cognition Assessment

Srivastava, Anshu; Yadav, Santosh K.; Borkar, Vibhor; Yadav, Abhishek; Yachha, Surender Kumar; Thomas, M. Albert; Rathore, Ram K.S.; Pandey, Chandra M.; Gupta, Rakesh K.

doi:10.1097/mpg.0b013e31825f4c3e

Cited by 15 publications

(31 citation statements)

References 34 publications

(50 reference statements)

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“…In a previous study on experimental trauma/hemorrhagic shock in genetically identical mice, we observed a high degree of variability in the raw circulating mediator data, but could identify distinct principal inflammatory drivers in animals receiving hemorrhagic shock from those subjected to sham cannulation [11] . In the present study, we affirm that the inflammatory response of a diverse cohort of PALF participants is highly variable [20] – [22] and that PCA could segregate inflammation patterns associated with different outcomes.…”

Section: Discussionsupporting

confidence: 78%

Analysis of Serum Inflammatory Mediators Identifies Unique Dynamic Networks Associated with Death and Spontaneous Survival in Pediatric Acute Liver Failure

et al. 2013

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BackgroundTools to predict death or spontaneous survival are necessary to inform liver transplantation (LTx) decisions in pediatric acute liver failure (PALF), but such tools are not available. Recent data suggest that immune/inflammatory dysregulation occurs in the setting of acute liver failure. We hypothesized that specific, dynamic, and measurable patterns of immune/inflammatory dysregulation will correlate with outcomes in PALF.MethodsWe assayed 26 inflammatory mediators on stored serum samples obtained from a convenience sample of 49 children in the PALF study group (PALFSG) collected within 7 days after enrollment. Outcomes were assessed within 21 days of enrollment consisting of spontaneous survivors, non-survivors, and LTx recipients. Data were subjected to statistical analysis, patient-specific Principal Component Analysis (PCA), and Dynamic Bayesian Network (DBN) inference.FindingsRaw inflammatory mediator levels assessed over time did not distinguish among PALF outcomes. However, DBN analysis did reveal distinct interferon-gamma-related networks that distinguished spontaneous survivors from those who died. The network identified in LTx patients pre-transplant was more like that seen in spontaneous survivors than in those who died, a finding supported by PCA.InterpretationThe application of DBN analysis of inflammatory mediators in this small patient sample appears to differentiate survivors from non-survivors in PALF. Patterns associated with LTx pre-transplant were more like those seen in spontaneous survivors than in those who died. DBN-based analyses might lead to a better prediction of outcome in PALF, and could also have more general utility in other complex diseases with an inflammatory etiology.

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Section: Discussionsupporting

confidence: 78%

Analysis of Serum Inflammatory Mediators Identifies Unique Dynamic Networks Associated with Death and Spontaneous Survival in Pediatric Acute Liver Failure

et al. 2013

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“…The impact of inflammatory response, oxidative stress, and disturbances in neurotransmitter function and auto regulation of cerebral blood flow/metabolism during ALF is becoming increasingly clear 6 , 7 , 36 . A recent study in pediatric acute viral hepatitis patients, while very small, is consistent with adult literature in identifying cognitive deficits tied to indicators of cerebral edema, pro-inflammatory cytokines, and ammonia levels 8 . More detailed analysis of medical and demographic factors (such as SES)in a larger, longitudinally assessed cohort will be a priority to tease apart several potential contributors to cognitive outcomes in PALF.…”

Section: Discussionsupporting

confidence: 70%

Neuropsychological Functioning and Health‐Related Quality of Life

Sorensen¹,

Neighbors

Zhang

et al. 2015

J. pediatr. gastroenterol. nutr.

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Objectives Pediatric acute liver failure (PALF) is a rare, but serious event with poorly understood functional outcomes. The goal was to determine the prevalence of reduced neuropsychological (NP) functioning and health-related quality of life (HRQOL) following PALF. Methods This multi-center study examined NP functioning and HRQOL 1 - 6 (median=3.8) years after PALF. Participants age 6 - 16 (median=9.9) years were recruited from the PALF registry and administered measures of intelligence (IQ), visual spatial/visual motor coordination, attention, executive function (EF), depression, and adaptive skills. HRQOL and fatigue were assessed using the Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL™4.0) and PedsQL™ Multidimensional Fatigue Scale. Results 36 patients participated;50% were male and 67% were white. Median age at PALF was 5.6 years. A history of grade 3 or 4 hepatic encephalopathy was reported in 5/36 (14%) participants and 23/36 (64%) received a liver transplant. Visual spatial ability was significantly better than norms (p=0.009), but motor coordination was worse (p=0.04). Teachers (p=0.04 to p < 0.0001) and parents (p=0.005) reported more executive deficits versus norms, and participants had worse attention (p=0.02). Participants did not differ significantly from norms on IQ, depression, or adaptive functioning. All child self-report PedsQL™ Generic Core and Fatigue scales were significantly lower than a matched healthy sample (p=0.001 to p < 0.0001) and parent proxy-report was lower on the Fatigue scales (p=0.001 to p < 0.0001). Conclusions Long-term PALF survivors demonstrate average IQ and visual spatial ability, but greater than expected impairments in motor skills, attention, EF, HRQOL, and fatigue.

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“…Several small, single center studies in PALF survivors have examined cognitive function in specific disease groups including acute viral hepatitis (4), Wilson disease (27), and Reye syndrome (28), but these findings are difficult to generalize to the broader group of diagnoses that lead to PALF. Srivastava et al examined 6 children with HE and CE demonstrated on advanced MRI and correlated findings with serial neurocognitive testing after recovery.…”

Section: Discussionmentioning

confidence: 99%

“…(1) (2) (3) A small case series of children surviving PALF secondary to viral hepatitis demonstrated significant cognitive deficits that improved in parallel with indicators of CE and circulating pro-inflammatory cytokine levels. (4)…”

mentioning

confidence: 99%

Health Related Quality of Life and Neurocognitive Outcomes in the First Year after Pediatric Acute Liver Failure

Sorensen

Neighbors

Hardison

et al. 2018

The Journal of Pediatrics

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Serial Evaluation of Children With ALF With Advanced MRI, Serum Proinflammatory Cytokines, Thiamine, and Cognition Assessment

Cited by 15 publications

References 34 publications

Analysis of Serum Inflammatory Mediators Identifies Unique Dynamic Networks Associated with Death and Spontaneous Survival in Pediatric Acute Liver Failure

Analysis of Serum Inflammatory Mediators Identifies Unique Dynamic Networks Associated with Death and Spontaneous Survival in Pediatric Acute Liver Failure

Neuropsychological Functioning and Health‐Related Quality of Life

Health Related Quality of Life and Neurocognitive Outcomes in the First Year after Pediatric Acute Liver Failure

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