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Carbohydrate-deficient transferrin is a sensitive marker of alcohol consumption in fatty liver disease

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Abstract

Background

The prevalence of nonalcoholic fatty liver disease (NAFLD) and alcohol-associated/related liver disease (ALD) with metabolic syndrome is increasing globally. Metabolic syndrome and excessive alcohol consumption synergically exacerbate liver pathologies; therefore, drinking-specific serum markers unaffected by liver injury or metabolic syndrome are essential for assessing alcohol consumption. We evaluated the ratio of carbohydrate-deficient transferrin to total transferrin (%CDT) in patients with fatty liver disease, particularly focusing on its correlation with metabolic factors (UMIN000033550).

Methods

A total of 120 patients with fatty liver disease, including ALD and NAFLD, were screened for alcohol misuse using the Alcohol Use Disorders Identification Test. Associations of metabolic syndrome-related factors and hepatic steatosis/liver stiffness with drinking markers, such as %CDT, gamma-glutamyl transferase (GGT), and mean corpuscular volume (MCV), were assessed using multiple linear regression analyses.

Results

%CDT significantly increased with 3–4 drinks/day. The optimal cutoff value for identifying non- to light drinkers was 1.78% (sensitivity, 71.8%; specificity, 83.7%; and area under the receiver operating characteristic curve [AUROC], 0.851), which was significantly higher than that for GGT. The cutoff value for identifying heavy drinkers was 2.08% (sensitivity, 65.5%; specificity, 86.8%; and AUROC, 0.815). Multiple regression analysis revealed that this proportion was negatively correlated with body mass index, whereas GGT and MCV were influenced by multiple factors involved in liver injury and dyslipidemia.

Conclusions

%CDT showed a strong correlation with alcohol consumption, independent of liver damage, steatosis/stiffness, or metabolic syndrome-related factors, indicating that it is a useful drinking marker for the accurate diagnosis of NAFLD and ALD.

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Availability of data and material

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Code availability

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Authors and Affiliations

  1. Department of Gastroenterology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Maki Morinaga, Kazuyoshi Kon, Akira Uchiyama, Hiroo Fukada, Kyoko Fukuhara, Reiko Yaginuma, Eisuke Nakadera, Shunhei Yamashina & Kenichi Ikejima

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  1. Maki Morinaga
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  2. Kazuyoshi Kon
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  3. Akira Uchiyama
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  8. Shunhei Yamashina
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Contributions

Material preparation: MM, KK, AU, HF, KF, RY, EN, and SY; data collection and analysis: MM and KK; manuscript drafting: KK; experiment supervision and paper review: KI.

Corresponding author

Correspondence to Kazuyoshi Kon.

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Conflict of interest

Maki Morinaga, Kazuyoshi Kon, Akira Uchiyama, Hiroo Fukada, Kyoko Fukuhara, Reiko Yaginuma, Eisuke Nakadera, Shunhei Yamashina, and Kenichi Ikejima declare that they have no Conflict interests.

Informed consent in studies with human subjects

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients for being included in the study.

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This article does not contain any studies with animal subjects.

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Supplementary Information

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12072_2022_10298_MOESM1_ESM.tif

Supplementary Fig. 1 ROC curve of %CDT limited to women. a) The ROC curves for detecting non- or light drinkers. The area under the ROC curve was 0.843 (95% CI, 0.714−0.971) for %CDT. b) The ROC curves for detecting heavy drinkers. The area under the ROC curve was 0.839 (95% CI, 0.683−0.994) for %CDT (n=38). ROC, receiver operating characteristics; %CDT, carbohydrate-deficient transferrin to total transferrin; CI, confidence interval (TIF 76357 kb)

12072_2022_10298_MOESM2_ESM.tif

Supplementary Fig. 2 ROC curve of %CDT limited to patients with BMI ≥25 kg/m2 . a) The ROC curves for detecting non- or light drinkers. The area under the ROC curve was 0.884 (95% CI, 0.754−1.013) for %CDT. b) The ROC curves for detecting heavy drinkers. The area under the ROC curve was 0.938 (95% CI, 0.867−1.001) for %CDT (n=50). ROC, receiver operating characteristics; %CDT, carbohydrate-deficient transferrin to total transferrin; BMI, body mass index; CI, confidence interval (TIF 76357 kb)

12072_2022_10298_MOESM3_ESM.tif

Supplementary Fig. 3 ROC curve of %CDT limited to patients with cirrhosis. a) The ROC curves for detecting non- or light drinkers. The area under the ROC curve was 0.857 (95% CI, 0.619−1.095) for %CDT. b) The ROC curves for detecting heavy drinkers. The area under the ROC curve was 0.839 (95% CI, 0.652−1.027) for %CDT (n=18). ROC, receiver operating characteristics; %CDT, carbohydrate-deficient transferrin to total transferrin; CI, confidence interval (TIF 76359 kb)

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Morinaga, M., Kon, K., Uchiyama, A. et al. Carbohydrate-deficient transferrin is a sensitive marker of alcohol consumption in fatty liver disease. Hepatol Int 16, 348–358 (2022). https://doi.org/10.1007/s12072-022-10298-8

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