Journal of Gastroenterology

, Volume 49, Issue 2, pp 295–304 | Cite as

Oral choline tolerance test as a novel noninvasive method for predicting nonalcoholic steatohepatitis

  • Kento Imajo
  • Masato Yoneda
  • Koji Fujita
  • Takaomi Kessoku
  • Wataru Tomeno
  • Yuji Ogawa
  • Yoshiyasu Shinohara
  • Yusuke Sekino
  • Hironori Mawatari
  • Yuichi Nozaki
  • Hiroyuki Kirikoshi
  • Masataka Taguri
  • Gen Toshima
  • Junichiro Takahashi
  • Satoru Saito
  • Koichiro Wada
  • Atsushi Nakajima
Original Article—Liver, Pancreas, and Biliary Tract



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.


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).


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.


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.


OCTT Plasma free choline levels NASH NAFLD Noninvasive test 



Alanine aminotransferase


Aspartate aminotransferase


Area under the receiver operating characteristic curve


Computed tomography


Diabetes mellitus


Free choline


Fasting plasma glucose


Homeostasis model for the assessment of insulin resistance


High performance liquid chromatography


Microsomal triglyceride transfer protein


Nonalcoholic fatty liver disease


Nonalcoholic fatty liver disease activity score


Nonalcoholic steatohepatitis


Negative predictive value


Oral choline tolerance test


Positive predictive value


Receiver operating characteristic


Standard deviation






Simple steatosis




Very low density lipoprotein



The skillful technical assistance of Machiko Hiraga is gratefully acknowledged. This work was supported in part by a grant program “Collaborative Development of Innovative Seeds” from the Japan Science and Technology Agency to Atsushi Nakajima.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

535_2013_776_MOESM1_ESM.pdf (91 kb)
Supplementary material 1 (PDF 92 kb)


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Copyright information

© Springer Japan 2013

Authors and Affiliations

  • Kento Imajo
    • 1
  • Masato Yoneda
    • 1
  • Koji Fujita
    • 1
  • Takaomi Kessoku
    • 1
  • Wataru Tomeno
    • 1
  • Yuji Ogawa
    • 1
  • Yoshiyasu Shinohara
    • 1
  • Yusuke Sekino
    • 1
  • Hironori Mawatari
    • 1
  • Yuichi Nozaki
    • 1
  • Hiroyuki Kirikoshi
    • 1
  • Masataka Taguri
    • 2
  • Gen Toshima
    • 3
  • Junichiro Takahashi
    • 3
  • Satoru Saito
    • 1
  • Koichiro Wada
    • 4
  • Atsushi Nakajima
    • 1
  1. 1.Division of GastroenterologyYokohama City University Graduate School of MedicineYokohamaJapan
  2. 2.Division of Biostatistics and EpidemiologyYokohama City University Graduate School of MedicineYokohamaJapan
  3. 3.Skylight Biotech, IncAkitaJapan
  4. 4.Department of Pharmacology, Graduate School of DentistryOsaka UniversitySuitaJapan

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