Serum β-klotho is a potential biomarker for diagnosing alcoholic liver disease and differentiating from nonalcoholic fatty liver disease

Background Alcoholic liver disease (ALD), with the control of infectious liver disease and the improvement in living standards, is emerging as a significant liver disease posing a threat to public health. Besides, ALD often overlaps or coexists with nonalcoholic fatty liver disease (NAFLD), however,...

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Main Authors: Chengmei Fang, Xin Miao, Chuyan Peng, Zhenguo Xie, Fuzhen Zhao, Tian Chen, Wenjin Zhang, Xiaofei Bi, Xuan An, Guicheng Wu
Format: Article
Language:English
Published: PeerJ Inc. 2025-08-01
Series:PeerJ
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Online Access:https://peerj.com/articles/19779.pdf
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author Chengmei Fang
Xin Miao
Chuyan Peng
Zhenguo Xie
Fuzhen Zhao
Tian Chen
Wenjin Zhang
Xiaofei Bi
Xuan An
Guicheng Wu
author_facet Chengmei Fang
Xin Miao
Chuyan Peng
Zhenguo Xie
Fuzhen Zhao
Tian Chen
Wenjin Zhang
Xiaofei Bi
Xuan An
Guicheng Wu
author_sort Chengmei Fang
collection DOAJ
description Background Alcoholic liver disease (ALD), with the control of infectious liver disease and the improvement in living standards, is emerging as a significant liver disease posing a threat to public health. Besides, ALD often overlaps or coexists with nonalcoholic fatty liver disease (NAFLD), however, due to the lack of specific non-invasive biomarkers and the fact that drinkers’ self-reported alcohol consumption is often concealed, the identification of ALD and NAFLD is sometimes not easy. This study aims to explore a new specific serum biomarker to more easily diagnose ALD and differentiate it from NAFLD. Subjects and Methods A total of 204 serum samples were collected, including 70 from ALD patients, 68 from NAFLD patients and 66 from healthy controls (HC). Serum β-klotho (sKLB) levels were measured using the enzyme-linked immunosorbent assay (ELISA). The diagnostic performance of potential biomarkers was evaluated using the area under the receive operating characteristic curve (AUROC). Results The levels of sKLB were significantly elevated (1,332.12 (410.40, 2,687.00) pg/mL, p < 0.001) in ALD patients and significantly reduced in NAFLD patients (47.82 (32.76, 77.11) pg/mL, p = 0.018) compared to the healthy controls. The AUROC for sKLB in diagnosing ALD is 0.927, which was higher than that for the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (0.672) and γ-glutamyl transpeptidase (GGT) (0.891). The combined AUROC for sKLB + AST/ALT, sKLB + GGT, and AST/ALT ratio + GGT in diagnosing ALD were 0.924, 0.967 and 0.917, respectively. Conclusion sKLB is a potential biomarker for diagnosing ALD, and may aid in differentiating between ALD and NAFLD, when combined with GGT, sKLB offers enhanced diagnostic sensitivity and specificity for ALD.
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spelling doaj-art-c107e232ea934996af02171fc7e1a01a2025-08-20T02:55:10ZengPeerJ Inc.PeerJ2167-83592025-08-0113e1977910.7717/peerj.19779Serum β-klotho is a potential biomarker for diagnosing alcoholic liver disease and differentiating from nonalcoholic fatty liver diseaseChengmei Fang0Xin Miao1Chuyan Peng2Zhenguo Xie3Fuzhen Zhao4Tian Chen5Wenjin Zhang6Xiaofei Bi7Xuan An8Guicheng Wu9Department of Infectious Disease, Southwest Medical University, Sichuan, ChinaBlood Transfusion Department, Chongqing University Three Gorges Hospital, Chongqing, ChinaChongqing Municipality Clinical Research Center for Endocrinology and Metabolic Diseases, Chongqing University Three Gorges Hospital, Chongqing, ChinaDepartment of Pharmacy, Chongqing University Three Gorges Hospital, Chongqing, ChinaSchool of Medicine, Chongqing University, Chongqing, ChinaHealth Management Center, Chongqing University Three Gorges Hospital, Chongqing, ChinaChongqing Municipality Clinical Research Center for Endocrinology and Metabolic Diseases, Chongqing University Three Gorges Hospital, Chongqing, ChinaDepartment of Hepatology, Chongqing University Three Gorges Hospital, Chongqing, ChinaChongqing Municipality Clinical Research Center for Endocrinology and Metabolic Diseases, Chongqing University Three Gorges Hospital, Chongqing, ChinaDepartment of Infectious Disease, Southwest Medical University, Sichuan, ChinaBackground Alcoholic liver disease (ALD), with the control of infectious liver disease and the improvement in living standards, is emerging as a significant liver disease posing a threat to public health. Besides, ALD often overlaps or coexists with nonalcoholic fatty liver disease (NAFLD), however, due to the lack of specific non-invasive biomarkers and the fact that drinkers’ self-reported alcohol consumption is often concealed, the identification of ALD and NAFLD is sometimes not easy. This study aims to explore a new specific serum biomarker to more easily diagnose ALD and differentiate it from NAFLD. Subjects and Methods A total of 204 serum samples were collected, including 70 from ALD patients, 68 from NAFLD patients and 66 from healthy controls (HC). Serum β-klotho (sKLB) levels were measured using the enzyme-linked immunosorbent assay (ELISA). The diagnostic performance of potential biomarkers was evaluated using the area under the receive operating characteristic curve (AUROC). Results The levels of sKLB were significantly elevated (1,332.12 (410.40, 2,687.00) pg/mL, p < 0.001) in ALD patients and significantly reduced in NAFLD patients (47.82 (32.76, 77.11) pg/mL, p = 0.018) compared to the healthy controls. The AUROC for sKLB in diagnosing ALD is 0.927, which was higher than that for the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (0.672) and γ-glutamyl transpeptidase (GGT) (0.891). The combined AUROC for sKLB + AST/ALT, sKLB + GGT, and AST/ALT ratio + GGT in diagnosing ALD were 0.924, 0.967 and 0.917, respectively. Conclusion sKLB is a potential biomarker for diagnosing ALD, and may aid in differentiating between ALD and NAFLD, when combined with GGT, sKLB offers enhanced diagnostic sensitivity and specificity for ALD.https://peerj.com/articles/19779.pdfSerum β-klothoAlcoholic liver diseaseBiomarkerNonalcoholic fatty liver disease
spellingShingle Chengmei Fang
Xin Miao
Chuyan Peng
Zhenguo Xie
Fuzhen Zhao
Tian Chen
Wenjin Zhang
Xiaofei Bi
Xuan An
Guicheng Wu
Serum β-klotho is a potential biomarker for diagnosing alcoholic liver disease and differentiating from nonalcoholic fatty liver disease
PeerJ
Serum β-klotho
Alcoholic liver disease
Biomarker
Nonalcoholic fatty liver disease
title Serum β-klotho is a potential biomarker for diagnosing alcoholic liver disease and differentiating from nonalcoholic fatty liver disease
title_full Serum β-klotho is a potential biomarker for diagnosing alcoholic liver disease and differentiating from nonalcoholic fatty liver disease
title_fullStr Serum β-klotho is a potential biomarker for diagnosing alcoholic liver disease and differentiating from nonalcoholic fatty liver disease
title_full_unstemmed Serum β-klotho is a potential biomarker for diagnosing alcoholic liver disease and differentiating from nonalcoholic fatty liver disease
title_short Serum β-klotho is a potential biomarker for diagnosing alcoholic liver disease and differentiating from nonalcoholic fatty liver disease
title_sort serum β klotho is a potential biomarker for diagnosing alcoholic liver disease and differentiating from nonalcoholic fatty liver disease
topic Serum β-klotho
Alcoholic liver disease
Biomarker
Nonalcoholic fatty liver disease
url https://peerj.com/articles/19779.pdf
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