Metabolomic Signatures of Autoimmune Hepatitis in the Development of Cirrhosis

Frontiers in Medicine

article

Shan-shan Li¹  Xiao-he Xiao²  Zheng-sheng Zou²  Yue-cheng Yu³  Jia-bo Wang²  Ming Niu⁵  Jing Jing²  Ying Huang²  Zi-teng Zhang²  Shuai-shuai Chen²  Ge-zi Shi²  Xian He¹  Hai-zhu Zhang¹ 

[1] School of Pharmacy and Chemistry, Dali University;Department of Liver Diseases, Fifth Medical Center of Chinese PLA General Hospital;Liver Diseases Center of General Hospital of PLA Eastern Theater Command, Bayi Hospital Affiliated to Nanjing University of Chinese Medicine;School of Traditional Chinese Medicine, Capital Medical University;Department of Poisoning Treatment, Fifth Medical Center of Chinese PLA General Hospital

关键词: liver cirrhosis;    autoimmune hepatitis;    metabolomics;    metabolic pathway;    biomarkers;   

DOI  :  10.3389/fmed.2021.644376

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Objectives: Autoimmune hepatitis (AIH) can progress into severe outcomes, i.e., decompensated cirrhosis, from remarkable and persistent inflammation in the liver. Considering the energy-expending nature of inflammation, we tried to define the metabolomics signatures of AIH to uncover the underlying mechanisms of cirrhosis development and its metabolic biomarkers. Methods: Untargeted metabolomics analysis was performed on sera samples from 79 AIH patients at the stages (phenotypes) of non-cirrhosis ( n = 27), compensated cirrhosis ( n = 22), and decompensated cirrhosis ( n = 30). Pattern recognition was used to find unique metabolite fingerprints of cirrhosis with or without decompensation. Results: Out of the 294 annotated metabolites identified, 2 metabolic fingerprints were found associated with the development of cirrhosis (independent of the decompensated state, 42 metabolites) and the evolution of decompensated cirrhosis (out of 47 metabolites), respectively. The cirrhosis-associated fingerprints (eigenmetabolite) showed better capability to differentiate cirrhosis from non-cirrhosis patients than the aminotransferase-to-platelet ratio index. From the metabolic fingerprints, we found two pairs of metabolites (Mesobilirubinogen/6-Hydroxynicotinic acid and LysoPA(8:0/0:0)/7alpha-Hydroxycholesterol) calculated as ratio of intensities, which revealed robust abilities to identify cirrhosis or predict decompensated patients, respectively. These phenotype-related fingerprint metabolites featured fundamental energy supply disturbance along with the development of AIH cirrhosis and progression to decompensation, which was characterized as increased lipolysis, enhanced proteolysis, and increased glycolysis. Conclusions: Remodeling of metabolism to meet the liver inflammation-related energy supply is one of the key signatures of AIH in the development of cirrhosis and decompensation. Therefore, drug regulation metabolism has great potential in the treatment of AIH.

【 授权许可】

CC BY