Recovery of pan-genotypic and genotype-specific amino acid alterations in chronic hepatitis C after viral clearance: transition at the crossroad of metabolism and immunity

Ming Ling Chang*, Mei Ling Cheng, Su Wei Chang, Hsiang Yu Tang, Cheng Tang Chiu, Chau Ting Yeh, Ming Shi Shiao

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

9 引文 斯高帕斯(Scopus)

摘要

Recovery of amino acid (AA) metabolism and the associated clinical implications in chronic hepatitis C (CHC) patients with sustained virological response (SVR) following anti-hepatitis C virus (HCV) therapy remains elusive. A prospective cohort study was conducted on 222 CHC patients with SVR. Eighty-two age-matched male genotype 1 (G1) and G2 patients underwent paired serum metabolomics analyses with liquid chromatography–tandem mass spectrometry to examine AAs before and 24 weeks after anti-HCV therapy. Before anti-HCV therapy, G1 patients had a higher HCV RNA level than G2 patients. Twenty-four weeks post-therapy versus pre-therapy, repeated-measures ANOVA showed that the levels of alanine aminotransferase and most AAs decreased while those of lipids, glutamine and putrescine increased in CHC patients. The methionine sulfoxide/methionine ratio decreased, while the asymmetric dimethylarginine/arginine, glutamine/glutamate, citrulline/arginine, ornithine/arginine, kynurenine/tryptophan, tyrosine/phenylalanine and Fisher’s ratios increased. Genotype-specific subgroup analyses showed that valine and serotonin/tyrosine increased in G1 and that kynurenine and tyrosine/phenylalanine increased and sarcosine decreased in G2 patients. Viral clearance in CHC patients pan-genotypically restored fuel utilization by decelerating the tricarboxylic acid cycle. Following improvement in liver function, the urea, nitric oxide, methionine, and polyamine cycles were accelerated. The cardiometabolic risk attenuated, but the augmented kynurenine pathway activity could increase the oncogenesis risk. The trends in neurotransmitter formation differed between G1 and G2 patients after SVR. Moreover, the HCV-suppressing effect of valine was evident in G1 patients; with the exception of prostate cancer, the oncogenesis risk increased, particularly in G2 patients, at least within 24 weeks post-anti-HCV therapy.

原文英語
頁(從 - 到)291-302
頁數12
期刊Amino Acids
49
發行號2
DOIs
出版狀態已出版 - 01 02 2017

文獻附註

Publisher Copyright:
© 2016, Springer-Verlag Wien.

指紋

深入研究「Recovery of pan-genotypic and genotype-specific amino acid alterations in chronic hepatitis C after viral clearance: transition at the crossroad of metabolism and immunity」主題。共同形成了獨特的指紋。

引用此