First Definition of Reference Intervals of Liver Function Tests in China: A Large-Population-Based Multi-Center Study about Healthy Adults

Mu, Runqing; Chen, Wenxiang; Pan, Baishen; Wang, Lanlan; Hao, Xiaoke; Huang, Xianzhang; Qu, Rui; Zhao, Min; Zhang, Chuanbao; Guo, Wei; Huang, He; Ma, Yue; Zhang, Junhua; Zhang, Jie; Shang, Hong

doi:10.1371/journal.pone.0072916

Cited by 33 publications

(28 citation statements)

References 18 publications

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“…However, more parsimoniously, it is likely that the drivers of body composition are similar across populations but their relevance varies. Specifically, ALT is higher in Chinese than in Westerners 35–37 which might be relevant to the lower fat-free mass in Chinese than in Westerners, 38 although ethnic variation in both ALT and fat-free mass could just be due to chance. The use of summary statistics in the MR study, means we could not comprehensively assess the differences by age, sex or by baseline levels of liver enzymes; but we assessed the differences by sex observationally.…”

Section: Discussionmentioning

confidence: 97%

The effect of liver enzymes on body composition: a Mendelian randomization study

Liu

Yeung

Kwok

et al. 2019

Preprint

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Background: Higher alanine transaminase (ALT) is positively associated with diabetes but inversely associated with body mass index (BMI) in Mendelian randomization (MR) studies, suggesting liver function may affect body composition. To clarify, we assessed the association of liver function with muscle and fat mass observationally with two-sample MR as a validation.Methods: In the population-representative "Children of 1997" birth cohort, we used multivariable linear regression to assess the adjusted associations of ALT and alkaline phosphatase (ALP) (IU/L) at ~17.5 years with muscle mass (kg) and body fat percentage (%). Genetic variants predicting ALT, ALP and gamma glutamyltransferase (GGT) (100% change in concentration) were applied to fat-free and fat mass (kg) in the UK Biobank (n=~331,000) to obtain unconfounded estimates using MR.Results: Observationally, ALT was positively associated with muscle mass (0.11, 95% confidence interval (CI) 0.10 to 0.12) and fat percentage (0.15, 95% CI 0.13 to 0.17). ALP was inversely associated with muscle mass (-0.03, 95% CI -0.04 to -0.02) and fat percentage (-0.02, 95% CI -0.03 to -0.01). Using MR, ALT was inversely associated with fat-free mass (-0.41, 95% CI -0.64 to -0.19) and fat mass (-0.58, 95% CI -0.85 to -0.30). ALP was not clearly associated with body composition. GGT was positively associated with fat-free (0.30, 95% CI 0.01 to 0.06) and fat mass (0.41, 95% CI 0.10 to 0.71).Conclusion: ALT reducing fat-free mass provides a possible pathway for the positive association of ALT with diabetes, and suggests a potential target of intervention.

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Section: Discussionmentioning

confidence: 97%

The effect of liver enzymes on body composition: a Mendelian randomization study

Liu

Yeung

Kwok

et al. 2019

Preprint

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“…Additionally, the Sinton method was used by Manning et al while the Lahti method was preferred by Ridefelt et al [24][25]. There are also certain studies frequently using the standard statistical methods in the literature [26][27][28][29][30][31][32][33][34][35][36][37][38].…”

Section: Discussionmentioning

confidence: 99%

Determination of sub-groups in reference interval calculations and an application

Temel¹,

Kanik²,

Yıldırım³

et al. 2015

Turkish Journal of Biochemistry

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Objective: The main objective of this study is to determine the methods used for dividing reference data into sub-groups and propose a new solution. Therefore, the newly proposed method is used to determine age sub-groups while calculating the reference interval of AST variable.Methods: The data of this study are composed of the registered patients who applied only once to the polyclinics at the Health Research and Application Hospital, Clinical Bio-Chemistry Laboratory of Mersin University. The main variables selected for the study are sex, age and aspartate transaminase (AST). MARS 2.0 package software was used for the statistical analysis. Harris&Boyd method was used for sex and age while the MARS method was used for the determination of age sub-groups.Results: According to the Harris&Boyd method, it was concluded that it is not necessary to create sub-groups for sex and age variables. Age sub-groups are determined with the MARS method by taking into account the correlations between AST variables and age. Age sub-groups are calculated as 5-9, 10-18 and 19+. Correlation between the age and AST variable is investigated for these sub-groups. It is obtained that the correlation is statistically not significant for the 5-9 age group (p=0.3189), significant for the 10-18 age group (p<0.001) and significant for 19 and above (p<0.001).Conclusion: The selection of transformation and outlier value elimination method and especially determination criteria for separation of sub-groups are made according to researcher's subjective desicions in the application of many studies. Because of this reason, MARS can be used as an alternative and objective method for determining subgroups. In addition, results of MARS method being parallel with the findings of the producing company supported the usage of this method for determination of sub-groups.

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“…When similar studies in the literature are examined, the most important point missed is analyzing the tests one by one in the outliers or RI calculation [17,20]. In the related studies, we think that one of the reasons of the difference especially in the region-based comparisons could be not analyzing the correlations between tests.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, as in other studies in the literature, tests should be evaluated by considering together, not separately [1][2][3][4][5][6][7][8]16,17,20]. In our study, RIs of the individuals aged 18-70 were identified by a new Brought to you by | New York University Bobst Library Technical Services Authenticated Download Date | 10/8/15 9:48 AM approach.…”

Section: Discussionmentioning

confidence: 99%

“…In another study, the researchers measured ALP, total protein, albumin and total bilirubin values for the Chinese adult population, in addition to the three tests within the study [17]. They mentioned that they have established common reference intervals of liver function tests that are defined specifically for Chinese population and can be universally used among EQA-approved laboratories located all over China [17]. As seen in other studies in the literature, RI studies of Liver function tests are clinically very important.…”

Section: Introductionmentioning

confidence: 99%

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Comparison of classical and clustering based reference interval calculations for Aspartate Aminotransferase, Alanine Aminotransferase and Gamma-Glutamyl Transferase in serum / Aspartat Aminotransferaz, Alanin Aminotransferaz ve Gama Glutamil Transferaz serum için klasik ve kümelemeye dayalı referans aralık hesaplamalarının karşılaştırılması

Coşgun

Topçu²,

Lâleli³

2015

Turkish Journal of Biochemistry

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Objective: There are fixed rules applied to determine the reference intervals (RIs) of the biochemical tests. However, these rules lack for identifying subgroups within the reference population. Therefore, we suggest the clustering method, which determines the sub-groups by taking the correlations between the variables into account in the RIs calculations. In our study, it is aimed to compare the results of the RIs based on the clusters analysis with the results of the conventional method.Methods: The individuals who applied Ankara Düzen Laboratory for the check-up with normal Ultra Sono Grafi (USG) in 2012-2014 and who have had Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and G-Glutamyl Transferase (GGT); (U/L) results were included in this study. We have excluded the repeated applies of patients, only analyzed the first apply to the laboratory. Reference individuals are composed of 883 people. (610 male, 273 female, 18-70 years). Non-parametric methods were used to determine reference intervals. Fuzzy C-Means clustering method was used to identify sub-groups.Results: AST, ALT, GGT measurements for all of the check-up individuals were determined by non-parametric method for the three subgroups specified after the Fuzzy-C-Means clustering method and the entire group. According to the reference intervals obtained, the third sub-cluster derived from the group intended to be used as the reference population was observed as a cluster that is narrower, and has similar properties of the actual reference population. However, when the correlations between the tests in the sub-groups are considered, the correlations between GGT-ALT-AST have been observed to be higher while the correlation level between ALT-AST in the group proposed as a real reference population does not change.Conclusion: In the reference limit studies, instead of the determination of the reference interval for a single group designated as the reference population, we think that, the subgroups which are homogeneous within itself, heterogeneous between themselves should be set in in this group. In determining multiple sub-groups, the relationship between more than one test need to be taken into consideration, and the effect of clustering should be investigated.Özet: Amaç: Biyokimyasal testlerin referans aralıklarının belirlenmesi için kullanılan sabit kurallar bulunmaktadır. Ancak bu kuralların referans popülasyon içerisindeki alt grupların tanımlanmasında eksikleri bulunmaktadır. Bu nedenle RIs hesaplamasında değişkenler arasındaki korelasyonları göz önüne alarak alt grupları belirleyen küme-leme yöntemini önermekteyiz. Çalışmamızda kümele analizine dayalı referans aralıklar ile klasik yöntemin sonuçlarının karşılaştırılması amaçlanmıştır.

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First Definition of Reference Intervals of Liver Function Tests in China: A Large-Population-Based Multi-Center Study about Healthy Adults

Cited by 33 publications

References 18 publications

The effect of liver enzymes on body composition: a Mendelian randomization study

The effect of liver enzymes on body composition: a Mendelian randomization study

Determination of sub-groups in reference interval calculations and an application

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