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

• Published in: Journal of gastroenterology Vol. 49; no. 2; pp. 295 - 304
• Main Authors: Imajo, Kento, Yoneda, Masato, Fujita, Koji, Kessoku, Takaomi, Tomeno, Wataru, Ogawa, Yuji, Shinohara, Yoshiyasu, Sekino, Yusuke, Mawatari, Hironori, Nozaki, Yuichi, Kirikoshi, Hiroyuki, Taguri, Masataka, Toshima, Gen, Takahashi, Junichiro, Saito, Satoru, Wada, Koichiro, Nakajima, Atsushi
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.02.2014; Springer; Springer Nature B.V
• Subjects: Abdominal Surgery; Administration, Oral; Adult; Aged; Area Under Curve; Biliary Tract; Case-Control Studies; Choline; Choline - administration & dosage; Choline - blood; Colorectal Surgery; Ethylenediaminetetraacetic acid; Evaluation; Fasting; Fatty Liver - blood; Fatty Liver - diagnosis; Female; Fibrosis; Gastroenterology; Health aspects; Hepatology; Humans; Lipoproteins, VLDL - blood; Lipotropic Agents - administration & dosage; Lipotropic Agents - blood; Liver; Liver - pathology; Liver diseases; Male; Medical colleges; Medicine; Medicine & Public Health; Methods; Middle Aged; Non-alcoholic Fatty Liver Disease; Original Article—Liver; Pancreas; Physiological aspects; Predictive Value of Tests; ROC Curve; Surgical Oncology; Time Factors; Triglycerides - blood; OCTT; NAFLD; NASH; Plasma free choline levels; Noninvasive test
• ISSN: 0944-1174; 1435-5922; 1435-5922
• DOI: 10.1007/s00535-013-0776-3

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.