AUTHOR=Li Shan-shan , Niu Ming , Jing Jing , Huang Ying , Zhang Zi-teng , Chen Shuai-shuai , Shi Ge-zi , He Xian , Zhang Hai-zhu , Xiao Xiao-he , Zou Zheng-sheng , Yu Yue-cheng , Wang Jia-bo 

TITLE=Metabolomic Signatures of Autoimmune Hepatitis in the Development of Cirrhosis

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.644376

DOI=10.3389/fmed.2021.644376

ISSN=2296-858X

ABSTRACT=<p><bold>Objectives:</bold> 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.</p><p><bold>Methods:</bold> Untargeted metabolomics analysis was performed on sera samples from 79 AIH patients at the stages (phenotypes) of non-cirrhosis (<italic>n</italic> = 27), compensated cirrhosis (<italic>n</italic> = 22), and decompensated cirrhosis (<italic>n</italic> = 30). Pattern recognition was used to find unique metabolite fingerprints of cirrhosis with or without decompensation.</p><p><bold>Results:</bold> 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.</p><p><bold>Conclusions:</bold> 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.</p>