title: Liver breath tests non-invasively predict higher stages of non-alcoholic steatohepatitis.
abstract: Effectively assessing subtle hepatic metabolic functions by novel non-invasive tests might be of clinical utility in scoring NAFLD (non-alcoholic fatty liver disease) and in identifying altered metabolic pathways. The present study was conducted on 39 (20 lean and 19 obese) hypertransaminasemic patients with histologically proven NAFLD {ranging from simple steatosis to severe steatohepatitis [NASH (non-alcoholic steatohepatitis)] and fibrosis} and 28 (20 lean and eight overweight) healthy controls, who underwent stable isotope breath testing ([(13)C]methacetin and [(13)C]ketoisocaproate) for microsomal and mitochondrial liver function in relation to histology, serum hyaluronate, as a marker of liver fibrosis, and body size. Compared with healthy subjects and patients with simple steatosis, NASH patients had enhanced methacetin demethylation (P=0.001), but decreased (P=0.001) and delayed (P=0.006) ketoisocaproate decarboxylation, which was inversely related (P=0.001) to the degree of histological fibrosis (r=-0.701), serum hyaluronate (r=-0.644) and body size (r=-0.485). Ketoisocaproate decarboxylation was impaired further in obese patients with NASH, but not in patients with simple steatosis and in overweight controls. NASH and insulin resistance were independently associated with an abnormal ketoisocaproate breath test (P=0.001). The cut-off value of 9.6% cumulative expired (13)CO(2) for ketoisocaproate at 60 min was associated with the highest prediction (positive predictive value, 0.90; negative predictive value, 0.73) for NASH, yielding an overall sensitivity of 68% and specificity of 94%. In conclusion, both microsomal and mitochondrial functions are disturbed in NASH. Therefore stable isotope breath tests may usefully contribute to a better and non-invasive characterization of patients with NAFLD.
authors.affiliation: Clinica Medica A. Murri, Department of Internal Medicine, University of Bari Medical School, Bari, Italy. p.portincasa@semeiotica.uniba.it
authors.forename: Piero
authors.initials: P
authors.lastname: Portincasa
authors.forename: Ignazio
authors.initials: I
authors.lastname: Grattagliano
authors.forename: Bernhard H
authors.initials: BH
authors.lastname: Lauterburg
authors.forename: Vincenzo O
authors.initials: VO
authors.lastname: Palmieri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palasciano
authors.forename: Frans
authors.initials: F
authors.lastname: Stellaard
mesh_terms: D000081:Acetamides; D000328:Adult; D017677:Age Distribution; D015415:Biomarkers / Q000378:metabolism; D015992:Body Mass Index; D001835:Body Weight; D001944:Breath Tests / Q000379:methods*; D002208:Caproates; D002247:Carbon Isotopes; D005234:Fatty Liver / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008862:Microsomes, Liver / Q000502:physiology; D008875:Middle Aged; D008930:Mitochondria, Liver / Q000502:physiology; D009765:Obesity / Q000503:physiopathology; D050177:Overweight; D012720:Severity of Illness Index
chemical_list: D000081:Acetamides; D015415:Biomarkers; D002208:Caproates; D002247:Carbon Isotopes; C035495:methacetin; C034527:isocaproic acid