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

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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.

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Abbreviations

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

AUROC:

Area under the receiver operating characteristic curve

CT:

Computed tomography

DM:

Diabetes mellitus

fCh:

Free choline

FPG:

Fasting plasma glucose

HOMA-IR:

Homeostasis model for the assessment of insulin resistance

HPLC:

High performance liquid chromatography

MTTP:

Microsomal triglyceride transfer protein

NAFLD:

Nonalcoholic fatty liver disease

NAS:

Nonalcoholic fatty liver disease activity score

NASH:

Nonalcoholic steatohepatitis

NPV:

Negative predictive value

OCTT:

Oral choline tolerance test

PPV:

Positive predictive value

ROC:

Receiver operating characteristic

SD:

Standard deviation

Se:

Sensitivity

Sp:

Specificity

SS:

Simple steatosis

TG:

Triglyceride

VLDL:

Very low density lipoprotein

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Acknowledgments

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.

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The authors declare that they have no conflict of interest.

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Correspondence to Atsushi Nakajima.

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Imajo, K., Yoneda, M., Fujita, K. et al. Oral choline tolerance test as a novel noninvasive method for predicting nonalcoholic steatohepatitis. J Gastroenterol 49, 295–304 (2014). https://doi.org/10.1007/s00535-013-0776-3

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  • DOI: https://doi.org/10.1007/s00535-013-0776-3

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