Glutathione species and metabolomic prints in subjects with liver disease as biological markers for the detection of hepatocellular carcinoma.
The incidence of liver disease is increasing in USA. Animal models had shown glutathione species in plasma reflects liver glutathione state and it could be a surrogate for the detection of hepatocellular carcinoma (HCC).



The present study aimed to translate methods to the human and to explore the role of glutathione/metabolic prints in the progression of liver dysfunction and in the detection of HCC. Treated plasma from healthy subjects (n = 20), patients with liver disease (ESLD, n = 99) and patients after transplantation (LTx, n = 7) were analyzed by GC- or LC/MS. Glutathione labeling profile was measured by isotopomer analyzes of2H2O enriched plasma. Principal Component Analyzes (PCA) were used to determined metabolic prints.



There was a significant difference in glutathione/metabolic profiles from patients with ESLD vs healthy subjects and patients after LTx. Similar significant differences were noted on patients with ESLD when stratified by the MELD score. PCA analyses showed myristic acid, citric acid, succinic acid, l-methionine, d-threitol, fumaric acid, pipecolic acid, isoleucine, hydroxy-butyrate and glycolic, steraric and hexanoic acids were discriminative metabolites for ESLD-HCC+vs ESLD-HCC-subject status.



Glutathione species and metabolic prints defined liver disease severity and may serve as surrogate for the detection of HCC in patients with established cirrhosis.
Department of Surgery, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Department of Preventive Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Department of Surgery and Research, Cancer Treatment Centers of America, Chicago, IL, USA; Department of Biostatistics, Cancer Treatment Centers of America, Chicago, IL, USA. Electronic address: sanabriaJ@marshall.edu.
Juan R
JR
Sanabria
Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH, USA. Electronic address: komburajan@gmail.com.
Rajan S
RS
Kombu
Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH, USA. Electronic address: gxz35@case.edu.
Guo-Fang
GF
Zhang
Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH, USA. Electronic address: Yana.Sandlers@gmail.com.
Yana
Y
Sandlers
Department of Surgery and Research, Cancer Treatment Centers of America, Chicago, IL, USA; Department of Biostatistics, Cancer Treatment Centers of America, Chicago, IL, USA. Electronic address: Jizhou.Ai@ctca-hope.com.
Jizhou
J
Ai
Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH, USA. Electronic address: doctorrafaelibarra@gmail.com.
Rafael A
RA
Ibarra
Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH, USA. Electronic address: d_reemy@yahoo.com.
Rime
R
Abbas
Department of Surgery, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH, USA. Electronic address: kgoyal@gmail.com.
Kush
K
Goyal
Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Department of Metabolomics and Proteomics Core Facilities, Case Western Reserve University School of Medicine, Cleveland, OH, USA. Electronic address: hxb8@case.edu.
Henri
H
Brunengraber
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis / Q000601:surgery; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D058625:End Stage Liver Disease / Q000097:blood* / Q000175:diagnosis / Q000601:surgery; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005978:Glutathione / Q000097:blood*; D006801:Humans; D016018:Least-Squares Analysis; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D025341:Principal Component Analysis; D012720:Severity of Illness Index; D053719:Tandem Mass Spectrometry
D014408:Biomarkers, Tumor; D005978:Glutathione