Study of Carnitine/Acylcarnitine and Amino Acid Profile in Children and Adults With Acute Liver Failure

Sood, Vikrant; Rawat, Dinesh; Khanna, Rajeev; Sharma, Shvetank; Gupta, Prem K.; Alam, Seema; Sarin, Shiv Kumar

doi:10.1097/mpg.0000000000001510

Cited by 6 publications

(4 citation statements)

References 43 publications

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“…Diagnosis is facilitated by hypoketotic hypoglycemia and moderate hyperammonemia [ 41 , 42 ]. Some patients have elevated CPK levels and metabolic acidosis, attributable to renal tubular acidosis during acute episodes.…”

Section: Study Of Metabolites In the Diagnosis Of Fatty Acid Oxidation Defectsmentioning

confidence: 99%

Biochemical Markers for the Diagnosis of Mitochondrial Fatty Acid Oxidation Diseases

Ruíz-Sala

Quintana

2021

JCM

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Mitochondrial fatty acid β-oxidation (FAO) contributes a large proportion to the body’s energy needs in fasting and in situations of metabolic stress. Most tissues use energy from fatty acids, particularly the heart, skeletal muscle and the liver. In the brain, ketone bodies formed from FAO in the liver are used as the main source of energy. The mitochondrial fatty acid oxidation disorders (FAODs), which include the carnitine system defects, constitute a group of diseases with several types and subtypes and with variable clinical spectrum and prognosis, from paucisymptomatic cases to more severe affectations, with a 5% rate of sudden death in childhood, and with fasting hypoketotic hypoglycemia frequently occurring. The implementation of newborn screening programs has resulted in new challenges in diagnosis, with the detection of new phenotypes as well as carriers and false positive cases. In this article, a review of the biochemical markers used for the diagnosis of FAODs is presented. The analysis of acylcarnitines by MS/MS contributes to improving the biochemical diagnosis, both in affected patients and in newborn screening, but acylglycines, organic acids, and other metabolites are also reported. Moreover, this review recommends caution, and outlines the differences in the interpretation of the biomarkers depending on age, clinical situation and types of samples or techniques.

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Section: Study Of Metabolites In the Diagnosis Of Fatty Acid Oxidation Defectsmentioning

confidence: 99%

Biochemical Markers for the Diagnosis of Mitochondrial Fatty Acid Oxidation Diseases

Ruíz-Sala

Quintana

2021

JCM

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“…As shown in Figure 5F, accumulation of serum acylcarnitines was found in patients who had organ failure. Abnormal carnitine/acylcarnitine profile was also reported in patients with acute liver failure [27]. In addition, blood level of long-chain acetylcarnitines were positively correlated with liver cirrhosis in patients [28,29].…”

Section: Discussionmentioning

confidence: 77%

Serum Acylcarnitines Associated with High Short-Term Mortality in Patients with Alcoholic Hepatitis

et al. 2021

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Alcohol-related liver disease is one of the most prevalent liver diseases in the United States. Early stages of alcohol-related liver disease are characterized by accumulation of triglycerides in hepatocytes. Alcoholic hepatitis is a severe form of alcohol-related liver disease associated with significant morbidity and mortality. We sought to identify patients who are at greatest risk of death using serum lipids. First, we performed lipidomics analysis on serum samples collected from 118 patients with alcoholic hepatitis to identify lipid markers that are associated with high risk of death. Next, we performed gene set enrichment analysis on liver transcriptomics data to identify dysregulated lipid metabolism in patients who received liver transplantation. Finally, we built a random forest model to predict 30-day mortality using serum lipids. A total of 277 lipids were annotated in the serum of patients with alcoholic hepatitis, among which 25 were significantly different between patients in the deceased and alive groups. Five chemical clusters were significantly altered between the two groups. In particular, acylcarnitine cluster was enriched in the deceased group. Several hepatic lipid metabolism pathways were dysregulated in patients with alcoholic hepatitis who received liver transplantation. The mRNA expression of genes involved in the fatty acid transport into mitochondria and β-oxidation were also dysregulated. When predicting 30-day mortality in alcoholic hepatitis patients using serum lipids, we found that the area under the curve achieved 0.95. Serum lipids such as acylcarnitines may serve as biomarkers to identify alcoholic hepatitis patients at the greatest risk of death.

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“…We therefore propose that the promotion of lipid oxidation is key to the prevention of SLF, as confirmed by the loss of L-carnitine benefits on etomoxir treatment. Indeed, impaired fat burning is a regular finding in patients with acute liver failure of various etiologies, 41 whereas genetic CPT1A deficiency predisposes to steatosis, hypoglycemia, encephalopathy, and liver failure. 42 Overall, our findings support a model in which the increased inflow of venous blood causes immediate hypoxia, which via HIF2A counteracts efficient lipid oxidation and thereby creates an environment inadequate at covering the energy demands of a growing and metabolizing tissue.…”

Section: Discussionmentioning

confidence: 99%

Normalization of lipid oxidation defects arising from hypoxia early posthepatectomy prevents liver failure in mouse

Birrer

Kachaylo²,

Breuer³

et al. 2023

American Journal of Transplantation

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Study of Carnitine/Acylcarnitine and Amino Acid Profile in Children and Adults With Acute Liver Failure

Abstract: FAODs are not uncommon in ALF with a suggested prevalence of approximately 5.5%. FAODs can cause ALF or modify the natural course of ALF caused by other etiologies. Serum hyperaminoacidemia and low serum free carnitine may predict poor outcome in patients with acute liver failure.

Cited by 6 publications

References 43 publications

Biochemical Markers for the Diagnosis of Mitochondrial Fatty Acid Oxidation Diseases

Biochemical Markers for the Diagnosis of Mitochondrial Fatty Acid Oxidation Diseases

Serum Acylcarnitines Associated with High Short-Term Mortality in Patients with Alcoholic Hepatitis

Normalization of lipid oxidation defects arising from hypoxia early posthepatectomy prevents liver failure in mouse

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