Acute liver failure in under two year-olds - are there markers of metabolic disease on admission?

Brett, Ana; Pinto, Carla; Carvalho, Leonor; Garcia, Paula; Diogo, Luísa; Gonçalves, Isabel

doi:10.1016/s1665-2681(19)31321-3

Cited by 17 publications

(18 citation statements)

References 22 publications

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“…Hegarty et al found increased bilirubin and decreased AST levels in galactosemia as opposed to decreased bilirubin and AST levels in tyrosinemia Type 1 22 . Some other studies reported that the bilirubin level is often increased, and hyperammonemia is frequently seen in patients with MD 2,6 . In our study, bilirubin and coagulation levels were significantly higher, and hyperammonemia was relatively more frequent in patients with MD, which is consistent with the literature.…”

Section: Discussionsupporting

confidence: 91%

“…In our study, bilirubin and coagulation levels were significantly higher, and hyperammonemia was relatively more frequent in patients with MD, which is consistent with the literature. According to the literature, hypoglycemia often occurred in patients with MD 2,6 . Moreover, hypoglycemia has been shown to be more severe in neonates with MD‐associated ALF 23 .…”

Section: Discussionmentioning

confidence: 99%

“…The incidence of MD in pediatric ALF patients has been reported to be 10–42.5% 3‐5 and to be relatively higher in children aged less than 2 years (43%) 6 . In older children, however, viral and toxic etiologies are more frequent 7 …”

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confidence: 99%

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Acute liver failure associated with metabolic diseases: A 10‐year single‐center experience

Güven

Sağ

Karagüzel

et al. 2020

Pediatrics International

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Background: Acute liver failure (ALF) is a rare multisystemic disease occurring in individuals with no history of liver disease, characterized by coagulopathy and / or hepatic encephalopathy secondary to acute liver injury. It is mostly caused by viral infections, drug intoxication, and metabolic diseases (MD), and can also have an indeterminate etiology. In this study, we aimed to evaluate the demographic and clinical characteristics and clinical outcomes of the patients that presented to our clinic with MD-associated ALF. Methods: This retrospective study reviewed age, gender, parental consanguinity, family history, presence of encephalopathy, laboratory parameters, and clinical outcomes of the patients that presented to our clinic between January 2009 and January 2019. Patients with MD-associated ALF were compared with patients in whom ALF was associated with other etiologies. Results: The study included 39 patients (53.8% boys; mean age + SD 6.13 AE 1.43 years). The total and direct bilirubin, international normalized ratio, and ammoniac levels were significantly higher in patients with MD than in the others (P < 0.05). Moreover, the incidences of hypoglycemia, death of a sibling and / or a family history of liver disease were also higher in patients with MD than in the others (P < 0.05). On the other hand, alanine aminotransferase (ALT) levels were significantly higher in patients with other etiologies. Conclusions: Metabolic diseases should be kept in mind in patients with a history of parental consanguinity and a positive family history of liver disease along with less increased alanine aminotransferase than expected, and increased bilirubin, international normalized ratio, and ammoniac levels and hypoglycemia. As the number of these parameters increases, the chance of diagnosis increases.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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Acute liver failure associated with metabolic diseases: A 10‐year single‐center experience

Güven

Sağ

Karagüzel

et al. 2020

Pediatrics International

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“…This hampers the ability to institute targeted therapy. Inborn errors of lipid metabolism are well-known causes of ALF and include respiratory chain (RC) disorders and fatty acid oxidation (FAO) defects causing energy deprivation of hepatocytes from impaired oxidative phosphorylation (OXPHOS) or fatty acid beta-oxidation, respectively [ 2 ]. In the OXPHOS pathway, a series of redox reactions is linked to electron transfer along the respiratory complex chain localized at the inner mitochondrial membrane.…”

Section: Introductionmentioning

confidence: 99%

Deep Sequencing Reveals Novel Genetic Variants in Children with Acute Liver Failure and Tissue Evidence of Impaired Energy Metabolism

Valencia

Wang

et al. 2016

PLoS ONE

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Background & AimsThe etiology of acute liver failure (ALF) remains elusive in almost half of affected children. We hypothesized that inherited mitochondrial and fatty acid oxidation disorders were occult etiological factors in patients with idiopathic ALF and impaired energy metabolism.MethodsTwelve patients with elevated blood molar lactate/pyruvate ratio and indeterminate etiology were selected from a retrospective cohort of 74 subjects with ALF because their fixed and frozen liver samples were available for histological, ultrastructural, molecular and biochemical analysis.ResultsA customized next-generation sequencing panel for 26 genes associated with mitochondrial and fatty acid oxidation defects revealed mutations and sequence variants in five subjects. Variants involved the genes ACAD9, POLG, POLG2, DGUOK, and RRM2B; the latter not previously reported in subjects with ALF. The explanted livers of the patients with heterozygous, truncating insertion mutations in RRM2B showed patchy micro- and macrovesicular steatosis, decreased mitochondrial DNA (mtDNA) content <30% of controls, and reduced respiratory chain complex activity; both patients had good post-transplant outcome. One infant with severe lactic acidosis was found to carry two heterozygous variants in ACAD9, which was associated with isolated complex I deficiency and diffuse hypergranular hepatocytes. The two subjects with heterozygous variants of unknown clinical significance in POLG and DGUOK developed ALF following drug exposure. Their hepatocytes displayed abnormal mitochondria by electron microscopy.ConclusionTargeted next generation sequencing and correlation with histological, ultrastructural and functional studies on liver tissue in children with elevated lactate/pyruvate ratio expand the spectrum of genes associated with pediatric ALF.

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“…Vomiting and retarded growth and development represent clues for early diagnosis of hereditary metabolic diseases. Mother's history of spontaneous abortion, sibling death, similar disease in siblings, significant increase in blood lactate, ammonia and INR, and moderate elevation of ALT and TB levels also provide diagnostic clues for identification of PALF caused by hereditary metabolic diseases[18][19][20]. Infectious factors are common causes of PALF in developing countries, among which viral hepatitis is most common[21,22].…”

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confidence: 99%

Gamma-glutamyl transpeptidase is a useful predictor in evaluating the prognosis in pediatric acute liver failure

Zhao

Bai

et al. 2019

Preprint

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Background and objective: Pediatric acute liver failure (PALF) progresses rapidly and has a poor prognosis. Therefore, simple, sensitive and specific clinical indicators are needed. Gamma-glutamyl transpeptidase (GGT) plays a role in predicting the prognosis in infantile cholestatic liver diseases. However, its role in predicting the prognosis in PALF remains unclear. Methods: In present study, children with PALF were divided into a normal GGT group and a high GGT group using the GGT level of 50 U/L as the demarcation line. Age, sex, serum total bilirubin, direct bilirubin, albumin, total bile acid, international normalized ratio (INR) and pediatric end-stage liver disease (PELD) score were compared between the 2 groups. In addition, GGT level was subjected to receiver operating characteristic (ROC) curve analysis, and the area under the curve and the optimal diagnostic cutoff value were calculated. Results: A total of 41 children with PALF were enrolled in the study. INR, PELD score and mortality rate were significantly higher in the normal GGT group in comparison to the high GGT group. GGT level had area under the ROC curve of 0.8194 (95% CI : 0.680-0.959); the optimal diagnostic cutoff values were 60 U/L. At the cutoff value, the sensitivity and specificity of GGT level in predicting the prognosis in PALF were 86.36% and 73.68% respectively. Conclusion: GGT exhibited high sensitivity and specificity in predicting the prognosis in PALF. It can be used as one useful prognostic indicator of PALF.

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Acute liver failure in under two year-olds - are there markers of metabolic disease on admission?

Cited by 17 publications

References 22 publications

Acute liver failure associated with metabolic diseases: A 10‐year single‐center experience

Acute liver failure associated with metabolic diseases: A 10‐year single‐center experience

Deep Sequencing Reveals Novel Genetic Variants in Children with Acute Liver Failure and Tissue Evidence of Impaired Energy Metabolism

Gamma-glutamyl transpeptidase is a useful predictor in evaluating the prognosis in pediatric acute liver failure

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