title: Plasma levels of homocysteine and cysteine increased in pediatric NAFLD and strongly correlated with severity of liver damage.
abstract: Non-alcoholic fatty liver disease (NAFLD) is a spectrum of metabolic abnormalities ranging from simple triglyceride accumulation in the hepatocytes to hepatic steatosis with inflammation, ballooning and fibrosis. It has been demonstrated that the pathogenesis of NAFLD involves increased oxidative stress, with consumption of the major cellular antioxidant, glutathione (GSH). Liver has a fundamental role in sulfur compound metabolism, although the data reported on plasma thiols status in NAFLD are conflicting. We recruited 63 NAFLD patients, and we analyzed all plasma thiols, such as homocysteine (Hcy), cysteine (Cys), cysteinylglycine (CysGly) and GSH, by high-performance liquid chromatography (HPLC) with fluorescence detection. Hcy, Cys and CysGly plasma levels increased in NAFLD patients (p < 0.0001); whereas GSH levels were decreased in NAFLD patients when compared to controls (p < 0.0001). On the contrary, patients with steatohepatitis exhibited lower levels of Hcy and Cys than subjects without. Furthermore, a positive correlation was found between Hcy and Cys and the presence of fibrosis in children with NAFLD. Taken together, these data demonstrated a defective hepatic sulfur metabolism in children with NAFLD, and that high levels of Hcy and Cys probably correlates with a pattern of more severe histological liver damage, due to mechanisms that require further studies.
authors.affiliation: Metabolomics and Proteomics Unit, "Bambino Gesù" Children's Hospital, IRCCS, Rome 00165, Italy. anna.pastore@opbg.net.
authors.forename: Anna
authors.initials: A
authors.lastname: Pastore
authors.affiliation: Liver Research Unit, "Bambino Gesù" Children's Hospital, IRCCS, Rome 00165, Italy. anna.alisi@opbg.net.
authors.forename: Anna
authors.initials: A
authors.lastname: Alisi
authors.affiliation: Metabolomics and Proteomics Unit, "Bambino Gesù" Children's Hospital, IRCCS, Rome 00165, Italy. gianna.digiovamberardino@opbg.net.
authors.forename: Gianna
authors.initials: G
authors.lastname: di Giovamberardino
authors.affiliation: Liver Research Unit, "Bambino Gesù" Children's Hospital, IRCCS, Rome 00165, Italy. annalisa.crudele@gmail.com.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Crudele
authors.affiliation: Liver Research Unit, "Bambino Gesù" Children's Hospital, IRCCS, Rome 00165, Italy. sara.ceccarelli@opbg.net.
authors.forename: Sara
authors.initials: S
authors.lastname: Ceccarelli
authors.affiliation: Liver Research Unit, "Bambino Gesù" Children's Hospital, IRCCS, Rome 00165, Italy. nadia.panera@opbg.net.
authors.forename: Nadia
authors.initials: N
authors.lastname: Panera
authors.affiliation: Metabolomics and Proteomics Unit, "Bambino Gesù" Children's Hospital, IRCCS, Rome 00165, Italy. carlo.dionisivici@opbg.net.
authors.forename: Carlo
authors.initials: C
authors.lastname: Dionisi-Vici
authors.affiliation: Liver Research Unit, "Bambino Gesù" Children's Hospital, IRCCS, Rome 00165, Italy. valerio.nobili@opbg.net.
authors.forename: Valerio
authors.initials: V
authors.lastname: Nobili
mesh_terms: D002648:Child; D003545:Cysteine / Q000097:blood*; D004151:Dipeptides / Q000097:blood; D005978:Glutathione / Q000097:blood; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008099:Liver / Q000473:pathology*; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000473:pathology
chemical_list: D004151:Dipeptides; D006710:Homocysteine; C028505:cysteinylglycine; D005978:Glutathione; D003545:Cysteine