CN-122017071-A - Endogenous substance used as biomarker for alcohol-related liver diseases and control application thereof

Abstract

The invention belongs to the technical field of biological medicine, and relates to a new application of an endogenous substance in alcohol-related liver diseases (ALD). The invention provides for the first time that endogenous substances with regular concentration changes in the ALD process can be used as biomarkers for assisting diagnosis and/or stage evaluation of ALD, and exogenous supplementation of the endogenous substances has a prevention and treatment effect on ALD and has dual values of being used as excellent biomarkers and effective therapeutic agents. Such substances include, but are not limited to, taurochenodeoxycholic acid (TCDCA), dehydroepiandrosterone-sulfate (DHEA-S), and the like, wherein the serum concentration of TCDCA increases significantly with disease progression, while the concentration of DHEA-S decreases significantly. The diagnostic value of the substances on ALD is obviously superior to that of the traditional liver injury markers, and exogenous supplementation can obviously improve ethanol-induced liver cell injury and mouse liver pathological changes. The invention provides a brand new strategy for the accurate diagnosis and prevention of ALD.

Inventors

• YOU YILIN
• KANG XIPING
• ZHAN JICHENG
• HUANG WEIDONG
• XUE HUIMIN
• HONG KEXIN
• TANG YUNYU

Assignees

• 中国农业大学

Dates

Publication Date

20260512

Application Date

20260214

Claims (10)

1. 1. The use of a class of endogenous substances that regularly change during the course of alcohol-related liver disease (ALD) as biomarkers for aiding diagnosis and/or staged evaluation of ALD.
2. 2. The use according to claim 1, wherein the use is effected by detecting the concentration of the endogenous substance in a blood sample of the subject.
3. 3. The use according to claim 1 or 2, wherein the regular change comprises a significant increase or decrease in concentration with increasing severity of the disease.
4. 4. The use according to claim 1, wherein the endogenous substances include bile acids and steroid hormones.
5. 5. The use according to claim 4, wherein the bile acid is taurochenodeoxycholic acid (TCDCA).
6. 6. The use according to claim 4, wherein the steroid hormone is dehydroepiandrosterone-sulfate (DHEA-S).
7. 7. The use of a class of endogenous substances that regularly change during the course of ALD in the manufacture of a medicament for the prevention and/or treatment of ALD.
8. 8. The use according to claim 7, wherein the endogenous substances include bile acids and steroid hormones.
9. 9. The use according to claim 8, wherein the bile acid is taurochenodeoxycholic acid (TCDCA).
10. 10. The use according to claim 8, wherein the steroid hormone is dehydroepiandrosterone-sulfate (DHEA-S).

Description

Endogenous substance used as biomarker for alcohol-related liver diseases and control application thereof Technical Field The invention belongs to the technical field of biological medicine. Relates to an endogenous substance with regular concentration change in the course of alcohol-related liver diseases, which can be used as a biomarker for assisting diagnosis and/or stage evaluation of alcohol-related liver diseases, and exogenous supplementation of the endogenous substance has prevention and treatment effects on alcohol-related liver diseases. Background Alcohol-related liver disease (Alcoholic LIVER DISEASE, ALD) is a series of chronic liver diseases caused by long-term excessive alcohol consumption, and its disease spectrum includes alcoholic fatty liver, alcoholic hepatitis, liver fibrosis, cirrhosis and even hepatocellular carcinoma, which has become a globally important public health problem. In China, ALD is particularly burdened with disease, and this challenge has been met. However, current clinical management of ALD still faces two major core challenges and unmet needs, namely, the first, lack of high-sensitivity, high-specificity early diagnosis and accurate stage biomarkers, and the lack of objective, specific biomarkers to effectively judge whether liver injury is caused by alcohol in addition to the history of detailed interrogation in clinic. Current diagnostic ALD relies primarily on the confirmation of a history of long-term excessive drinking. However, patients often have inaccurate medical history acquisition due to hidden or underestimated drinking volumes from psycho-social factors. More importantly, no blood detection index can be used as a specific serological marker to clearly indicate that liver injury is caused by alcohol in clinic. This makes diagnosis complicated and uncertain because doctors often need to exclude other liver diseases (such as non-alcoholic fatty liver disease, viral hepatitis, etc.) when distinguishing the etiology. Current clinically dependent biochemical indicators of liver function (e.g., aspartate aminotransferase (ASPARTATE AMINOTRANSFERASE, AST), alanine aminotransferase (Alanine Aminotransferase, ALT), etc.) are insensitive to early ALD and lack specificity, making it difficult to accurately distinguish simple fatty liver from high risk status that is about to progress to hepatitis, cirrhosis, etc. Imaging examination is limited in terms of early fibrosis and inflammation. This directly results in a large number of sub-clinical or early ALD patients being missed, missing the optimal window of intervention. Second, targeted therapeutic agents are extremely deficient. Although alcohol withdrawal is the cornerstone of ALD treatment, patient compliance is poor and pure alcohol withdrawal effect is limited for significant liver damage that has developed. Currently, there is no worldwide collection of targeted therapeutic drugs specifically targeted to the key pathogenesis of ALD. The clinical treatment means are very limited, mainly uses glucocorticoid (used for severe alcoholic hepatitis) and symptomatic support treatment, has unsatisfactory curative effect and has great side effect. Therefore, the development of novel biomarkers for ALD early diagnosis/staging and safe and effective prophylactic and therapeutic drugs is a significant challenge and urgent need in the current clinic. Existing studies have focused on exogenous compounds or single known pathways, and lack the ability to discover targets that have both diagnostic and therapeutic value from the perspective of systemic endogenous substance changes. In particular, no systematic report is made on the basis of the dynamic change rule of endogenous substances in ALD, and the endogenous substances are simultaneously used as biomarkers and control medicines. Disclosure of Invention In view of this, the present invention provides a new class of endogenous substances, the core of which is to propose and verify an innovative idea that endogenous substances with significant and regular concentration changes during ALD process are valuable resource libraries for the discovery of "dual-function" molecules with both excellent diagnostic/staging value and effective therapeutic potential. Based on the above, the invention particularly provides application of the substances as ALD biomarkers and prevention and treatment medicines, and provides a brand new strategy and substance basis for ALD accurate diagnosis and effective prevention and treatment. In order to achieve the above object, the present invention provides the following technical solutions: the invention provides the use of a class of endogenous substances that undergo regular changes in the course of alcohol-related liver disease (ALD) as biomarkers for aiding diagnosis and/or staged evaluation of ALD. In some embodiments of the invention, the above-described use is effected by detecting the concentration of said endogenous substance in a blood sam