title: Oral choline tolerance test as a novel noninvasive method for predicting nonalcoholic steatohepatitis.
abstract: BACKGROUND
  Although therapeutic intervention for nonalcoholic steatohepatitis (NASH) at an early stage is important owing to the progressive nature of the disease, diagnosis using noninvasive methods remains difficult. We previously demonstrated NASH specific impairment of choline metabolism and the use of fasting plasma free choline (fCh) levels for NASH diagnosis. Here, we investigated the utility of an oral choline tolerance test (OCTT), based on disordered choline metabolism, as a novel noninvasive method for NASH diagnosis.
  
  
  METHODS
  Sixty-five patients with biopsy proven nonalcoholic fatty liver disease (NAFLD) and 17 healthy controls were enrolled. Blood samples were obtained from all subjects five times during the OCTT (before and 1, 2, 3, and 4 h after oral loading with 260 mg choline).
  
  
  RESULTS
  Four-hour fCh levels after oral loading choline were markedly increased in NASH patients, compared with non-NASH subjects. For detecting NASH, compared with non-NASH subjects, the area under the curve for 4-h fCh levels was 0.829 on receiver operating characteristic (ROC) analysis. The cut-off level for NASH diagnosis was ≥0.16 mg/dL, and the sensitivity, specificity, positive predictive value, and negative predictive value were 80.1, 82.6, 78.4, and 84.4 %, respectively. Moreover, 4-h fCh levels were significantly associated with the disease activity based on NAFLD activity score in patients with NAFLD.
  
  
  CONCLUSIONS
  Four-hour fCh levels obtained by an OCTT reflect a NASH specific disorder of choline metabolism, suggesting that the OCTT is a novel and useful noninvasive method for diagnosing NASH at an early stage with sufficient accuracy for clinical practice.
authors.affiliation: Division of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan.
authors.forename: Kento
authors.initials: K
authors.lastname: Imajo
authors.forename: Masato
authors.initials: M
authors.lastname: Yoneda
authors.forename: Koji
authors.initials: K
authors.lastname: Fujita
authors.forename: Takaomi
authors.initials: T
authors.lastname: Kessoku
authors.forename: Wataru
authors.initials: W
authors.lastname: Tomeno
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Shinohara
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sekino
authors.forename: Hironori
authors.initials: H
authors.lastname: Mawatari
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Nozaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kirikoshi
authors.forename: Masataka
authors.initials: M
authors.lastname: Taguri
authors.forename: Gen
authors.initials: G
authors.lastname: Toshima
authors.forename: Junichiro
authors.initials: J
authors.lastname: Takahashi
authors.forename: Satoru
authors.initials: S
authors.lastname: Saito
authors.forename: Koichiro
authors.initials: K
authors.lastname: Wada
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakajima
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D016022:Case-Control Studies; D002794:Choline / Q000008:administration & dosage / Q000097:blood; D005215:Fasting; D005234:Fatty Liver / Q000097:blood / Q000175:diagnosis*; D005260:Female; D005355:Fibrosis; D006801:Humans; D008079:Lipoproteins, VLDL / Q000097:blood; D008082:Lipotropic Agents / Q000008:administration & dosage / Q000097:blood; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D011237:Predictive Value of Tests; D012372:ROC Curve; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D008079:Lipoproteins, VLDL; D008082:Lipotropic Agents; D014280:Triglycerides; D002794:Choline