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.
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.
Division of Hepatology, Department of Gastroenterology and Hepatology, Liver Research Center, Chang Gung Memorial Hospital, No 5, Fu Hsing Street, Kuei Shan, Taoyuan, Taiwan, ROC. mlchang8210@gmail.com.|Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC. mlchang8210@gmail.com.
Ming-Ling
ML
Chang
Department of Biomedical Sciences, Chang Gung University, 259 Wen-Hua 1st Road, Kwei-Shan, Taoyuan, 333, Taiwan, ROC. chengm@mail.cgu.edu.tw.|Metabolomics Core Laboratory, Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan, ROC. chengm@mail.cgu.edu.tw.|Clinical Phenome Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC. chengm@mail.cgu.edu.tw.
Mei-Ling
ML
Cheng
Clinical Informatics and Medical Statistics Research Center, Chang Gung University, Taoyuan, Taiwan, ROC.|Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
Su-Wei
SW
Chang
Metabolomics Core Laboratory, Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan, ROC.
Hsiang-Yu
HY
Tang
Division of Hepatology, Department of Gastroenterology and Hepatology, Liver Research Center, Chang Gung Memorial Hospital, No 5, Fu Hsing Street, Kuei Shan, Taoyuan, Taiwan, ROC.
Cheng-Tang
CT
Chiu
Division of Hepatology, Department of Gastroenterology and Hepatology, Liver Research Center, Chang Gung Memorial Hospital, No 5, Fu Hsing Street, Kuei Shan, Taoyuan, Taiwan, ROC.
Chau-Ting
CT
Yeh
Department of Biomedical Sciences, Chang Gung University, 259 Wen-Hua 1st Road, Kwei-Shan, Taoyuan, 333, Taiwan, ROC. msshiao@mail.cgu.edu.tw.
Ming-Shi
MS
Shiao
D000328:Adult; D000596:Amino Acids / Q000378:metabolism*; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D012367:RNA, Viral; D053719:Tandem Mass Spectrometry
D000596:Amino Acids; D012367:RNA, Viral
Amino acids; Genotype; HCV; LC–MS/MS; Targeted metabolomics