FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4200310358> ?p ?o ?g. }

• W4200310358 endingPage "461" @default.
• W4200310358 startingPage "459" @default.
• W4200310358 abstract "The occasional finding of elevated serum aminotransferase values in individuals without symptoms is a more and more broadening phenomenon, particularly in areas where preventive medicine results in frequent health screenings that include liver enzyme measurement. In most cases, hypertransaminasaemia is related to liver cell injury, with alanine aminotransferase (ALT) values generally more increased than those of aspartate aminotransferase (AST).1 In both adults and children, the AST to ALT ratio can be sporadically elevated in non-alcoholic steatohepatitis, liver fibrosis/cirrhosis and Wilson disease, but their ratio typically does not exceed two. In the adult population, an AST to ALT ratio ≥2:1 may indicate alcohol abuse and alcoholic liver disease especially when it is associated with an elevated gamma-glutamyl transferase (GGT) activity. When AST values are higher than ALT, sources other than liver should however also be considered, including cardiac, muscular, haematological, renal, cerebral and endocrine cells/organs. In these cases, serum AST levels increase jointly with some other associated enzymes depending on the pathology, for example, lactate dehydrogenase in heart disease or haemolysis, creatine phosphokinase and/or aldolase in muscular diseases and/or intense exercise. AST released from cellular lysis comprises the cytosolic (cAST) and mitochondrial (mAST) isoenzymes, encoded by GOT1 (10q24) and GOT2 (16q12) genes respectively. The largest part of serum AST activity is cytosolic, while the increase of serum mAST indicates the extent of ischaemic necrosis better than cAST.2 When AST values are increased separately without an evident corresponding organ damage, finding the origin of this hyperAST may be extremely difficult to understand or solve. In such a puzzling scenario in which studies on large paediatric series are scarce, the article by Magen-Rimon and colleagues appearing in this issue of Acta Paediatrica3 is particularly welcome. In fact, these authors retrospectively reviewed the medical charts of 32 children diagnosed with prolonged isolated AST elevation (ranged 1.2–12 folds upper limit of normal). Similar to other literature studies and case series/reports, their patients needed to go an extensive traditional stepwise workup1 which included abdominal ultrasonographic studies, laboratory screening for major and minor hepatotropic viruses, autoimmunity, celiac disease, a quite large number of inborn errors of metabolism, and renal, muscular and haemolytic diseases as well. Using both polyethylene glycol (PEG) precipitation and ultrafiltration (UF) testing, at last hyperAST resulted most likely due to the presence of macroAST in approximately one of 4.5 patients (22%). The authors did not find differences in AST levels between patients with/without macro-AST.3 Although most of this information is not entirely new, the study contributes to shed further light on several aspects of macro-AST, a condition which is still frequently neglected and as such responsible for unnecessary costly, iterative and invasive evaluation, for example, the liver biopsy considered essential in one child of their series.4, 5 As shown in Table 1, macro-AST belongs to the group of the so-called macroenzymes which also include a number of other hepatic and non-hepatic enzymes as well. Macroenzymes are normal enzymes forming high molecular-mass complexes unable to undergo renal clearance because of their size, and, therefore, they persist in the serum causing interference with routine measurement and diagnostic confusion.6 As other macroenzymes, also macro-AST may be categorised in two types. In Type I, the pathogenesis appears to be likely autoimmunity related, with the Fab portion of immunoglobulins IgG, or IgM or Ig A targeting serum enzymes as antigens in the setting of a molecular mimicry phenomenon. In Type II, the macroenzymes are transiently formed when the enzyme either self-polymerises or associates with a foreign chemical, for example, a drug or the apoprotein moiety of lipoprotein carriers.5, 7 The prevalence of most macroenzymes is quite low, spanning 0.5%–2.5%; although they are generally described as an incidentaloma in healthy people, they have been associated also with various pathological conditions, mostly autoimmune or infectious in origin (Table 2). Macro-AST, specifically, has been reported to range between 13% and 60% of adults evaluated in tertiary centres for isolated elevation of AST levels.5 Except for rare reports (e.g., association with inflammatory bowel disease and Kawasaki disease), data suggest that in children and adolescents macro-AST is a benign condition and is not accompanying other disorders. The paper by Magen-Rimon and colleagues adds on to the few available data of paediatric macroAST series by reporting a macro-AST prevalence which is lower than, but quite comparable to, that of the large series of Caropreso et al. (i.e., 1 of 3), and may occur early in life.8 As in adults, macro-AST frequency should be considered cautiously because of a possible referral bias and of the numerous methods of macroenzymes testing4, 9-12 (Table 3). Magen-Rimon et al. studied their patients with PEG precipitation together with UF, and considered positive or negative only those sera with concordant results. Similar studies using the same cut-off of their PEG test showed that it was a valuable tool with good sensitivity and specificity having electrophoresis as the gold standard.8 The 5-year long-term follow-up of Magen-Rimon et al. patients, which in some way remains comparable to that of Caropreso et al.,8 is important because it allows to confirm a general benign course of this condition over the years. Even though macro-AST levels in some series show a natural fluctuation or a possible normalisation over time, in Magen-Rimon's study the macro-AST remained stably elevated. If this variance depends on the different type of macroenzyme (type 1 or 2) is still unclear because this issue has not been studied in most published series. Sera storage at 4°C for 1 week shows a decrease in AST levels >90% in case of macro-AST. This screening method is potentially useful to laboratories lacking the above more complex methodologies. Despite the description of familiar forms of macro-AST, its formation has not been confirmed to have a clearly defined inherited genetic basis. Recently, Kuleka et al. by screening patients with suspected familial macro-AST found a GOT1 missense variant (p. Gln208Glu and rs374966349) as a putative cause in more than half probands, while its prevalence in healthy controls was only 0.18%. Computational strategies showed that the amino acid at this position is a negatively charged glutamate which could plausibly be responsible for a strong anchorage of serum immunoglobulins on the GOT1 surface.2 Due to the positive results observed only in part of the families described by Kuleka, and others’ findings who were unable to find the presence of this mutation in a family with macro-AST,13 it is possible that familial macro-AST may have polygenic inheritance requiring further genetic research to solve this still unsolved puzzle.2 Magen Rimon and colleagues by studying a quite large sample of patients add to what we know about paediatric macro-AST.3 However, like other investigations on this topic, their well-designed study is not exempt from inevitable and evitable limitations, as the authors themselves acknowledge. The major inevitable limitations are the retrospective nature of the study and the poor generalisability (only Israelian participants). Evitable limitations are the lack of more detailed information about the possible aetiology of the remaining patients with macro-AST negative hyperAST. One could speculate that the variability of the upper reference limits of AST level during different periods of childhood might represent the extremes of distinct Gaussian distributions in the normal paediatric population at different ages.5 Precise data on the AST and ALT normal values for age and folds of increase of AST over ALT values in their series might have added weight to the authors’ conclusions and made possible more comparisons with other studies. Despite this, the article by Magen-Rimon et al. is of interest for at least two major indisputable reasons: (a) it quite clearly confirms the benign course of a prolonged elevation of paediatric isolated AST, in general, and of paediatric macro-AST, in particular, (b) it further confirms that isolated AST levels cannot be used to discriminate between negative, borderline or positive macro- AST, as even AST values slightly exceeding the upper reference range may be due to the macroenzyme presence.8 Based on all the above findings, the recommendation of avoiding extensive/invasive laboratory and imaging investigations in healthy children with prolonged isolated AST elevation appears reasonable also when macro-AST testing is not easily available. There is no conflict of interest regarding this manuscript. Claudia Mandato Pietro Vajro" @default.
• W4200310358 created "2021-12-31" @default.
• W4200310358 creator A5031935586 @default.
• W4200310358 creator A5076854299 @default.
• W4200310358 date "2021-12-22" @default.
• W4200310358 modified "2023-10-17" @default.
• W4200310358 title "Isolated aspartate aminotransferase elevation: Is it liver disease or what else?" @default.
• W4200310358 cites W1971807138 @default.
• W4200310358 cites W1996976860 @default.
• W4200310358 cites W2009889810 @default.
• W4200310358 cites W2011699954 @default.
• W4200310358 cites W2021834447 @default.
• W4200310358 cites W2045527225 @default.
• W4200310358 cites W2048047875 @default.
• W4200310358 cites W2062842253 @default.
• W4200310358 cites W2151994938 @default.
• W4200310358 cites W2735136444 @default.
• W4200310358 cites W2937112035 @default.
• W4200310358 cites W2969147725 @default.
• W4200310358 cites W3202818900 @default.
• W4200310358 doi "https://doi.org/10.1111/apa.16213" @default.
• W4200310358 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34935200" @default.
• W4200310358 hasPublicationYear "2021" @default.
• W4200310358 type Work @default.
• W4200310358 citedByCount "2" @default.
• W4200310358 countsByYear W42003103582023 @default.
• W4200310358 crossrefType "journal-article" @default.
• W4200310358 hasAuthorship W4200310358A5031935586 @default.
• W4200310358 hasAuthorship W4200310358A5076854299 @default.
• W4200310358 hasBestOaLocation W42003103581 @default.
• W4200310358 hasConcept C126322002 @default.
• W4200310358 hasConcept C2524010 @default.
• W4200310358 hasConcept C2777075537 @default.
• W4200310358 hasConcept C2778606649 @default.
• W4200310358 hasConcept C2910413745 @default.
• W4200310358 hasConcept C2992872382 @default.
• W4200310358 hasConcept C33923547 @default.
• W4200310358 hasConcept C37054046 @default.
• W4200310358 hasConcept C71924100 @default.
• W4200310358 hasConcept C90924648 @default.
• W4200310358 hasConceptScore W4200310358C126322002 @default.
• W4200310358 hasConceptScore W4200310358C2524010 @default.
• W4200310358 hasConceptScore W4200310358C2777075537 @default.
• W4200310358 hasConceptScore W4200310358C2778606649 @default.
• W4200310358 hasConceptScore W4200310358C2910413745 @default.
• W4200310358 hasConceptScore W4200310358C2992872382 @default.
• W4200310358 hasConceptScore W4200310358C33923547 @default.
• W4200310358 hasConceptScore W4200310358C37054046 @default.
• W4200310358 hasConceptScore W4200310358C71924100 @default.
• W4200310358 hasConceptScore W4200310358C90924648 @default.
• W4200310358 hasIssue "3" @default.
• W4200310358 hasLocation W42003103581 @default.
• W4200310358 hasLocation W42003103582 @default.
• W4200310358 hasOpenAccess W4200310358 @default.
• W4200310358 hasPrimaryLocation W42003103581 @default.
• W4200310358 hasRelatedWork W2166398269 @default.
• W4200310358 hasRelatedWork W2257083003 @default.
• W4200310358 hasRelatedWork W2349662989 @default.
• W4200310358 hasRelatedWork W2416296897 @default.
• W4200310358 hasRelatedWork W2423082347 @default.
• W4200310358 hasRelatedWork W2891664938 @default.
• W4200310358 hasRelatedWork W2980985206 @default.
• W4200310358 hasRelatedWork W307921490 @default.
• W4200310358 hasRelatedWork W4241478348 @default.
• W4200310358 hasRelatedWork W46103319 @default.
• W4200310358 hasVolume "111" @default.
• W4200310358 isParatext "false" @default.
• W4200310358 isRetracted "false" @default.
• W4200310358 workType "article" @default.