Oral choline tolerance test as a novel noninvasive method for predicting nonalcoholic steatohepatitis
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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.
KeywordsOCTT Plasma free choline levels NASH NAFLD Noninvasive test
Area under the receiver operating characteristic curve
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
Negative predictive value
Oral choline tolerance test
Positive predictive value
Receiver operating characteristic
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.
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