Plasma free choline is a novel non-invasive biomarker for early-stage non-alcoholic steatohepatitis: A multi-center validation study.
OBJECTIVE
Choline is a dietary component that is crucial for normal cellular function. Choline is predominantly absorbed from the small intestine and completely metabolized in the liver. We recently demonstrated that free choline (fCh) levels in blood reflect the level of phosphatidylcholine synthesis in the liver and is correlated with the onset of non-alcoholic steatohepatitis (NASH). Our aim here was to validate the utility of this biomarker for NASH diagnosis.


METHODS
Our cohort consisted of 110 patients with biopsy proven non-alcoholic fatty liver disease (NAFLD) from four centers across Japan and 25 age-matched healthy controls. Plasma fCh levels were measured using high-performance liquid chromatography.


RESULTS
Patients with diagnosed or borderline NASH had significantly increased plasma fCh levels when compared with control subjects, or patients not diagnosed with NASH. Interestingly, an association between plasma fCh levels and expression of microsomal triglyceride transfer protein, which catalyzes the transfer of triglyceride, was reflected in the markedly negative correlation between these two variables in patients with NAFLD. Moreover, the grade of liver steatosis and fibrosis stage increased with increasing plasma fCh levels (P < 0.05). The area under the receiver-operating characteristic (ROC) curves for NASH, including borderline diagnosis, was 0.811. Additionally, the areas under the ROC for fibrosis stage were 0.816 for >stage 1, 0.805 for >stage 2, 0.809 for >stage 3 and 0.818 for >stage 4.


CONCLUSIONS
Plasma fCh levels are closely related to the grade of liver steatosis and fibrosis, and predict NASH severity. Plasma fCh levels are therefore a potential diagnostic marker for early-stage NASH in clinical practice.
Division of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama             Skylight Biotech Inc, Akita             Center for Digestive and Liver Diseases, Nara City Hospital, Nara             Division of Gastroenterology, National Kyusyu Medical Center Hospital, Fukuoka             Division of Gastroenterology, NTT Medical Center, Tokyo             Department of Pharmacology, Graduate School of Dentistry, Osaka University, Osaka, Japan.
Kento
K
Imajo
Koji
K
Fujita
Masato
M
Yoneda
Yoshiyasu
Y
Shinohara
Kaori
K
Suzuki
Hironori
H
Mawatari
Junichiro
J
Takahashi
Yuichi
Y
Nozaki
Yoshio
Y
Sumida
Hiroyuki
H
Kirikoshi
Satoru
S
Saito
Makoto
M
Nakamuta
Nobuyuki
N
Matsuhashi
Koichiro
K
Wada
Atsushi
A
Nakajima