Lower circulating levels of dehydroepiandrosterone, independent of insulin resistance, is an important determinant of severity of non-alcoholic steatohepatitis in Japanese patients.
OBJECTIVE
The biological basis of variability in histological progression of non-alcoholic fatty liver disease (NAFLD) remains unknown. Dehydroepiandrosterone (DHEA), the most abundant steroid hormone, has been shown to influence sensitivity to reactive oxygen species, insulin sensitivity and expression of peroxisome proliferator-activated receptor-α. Our aim was to determine whether more histologically advanced NAFLD is associated with low circulating levels of DHEA in Japanese patients.


METHODS
Serum samples were obtained in 133 Japanese patients with biopsy-proven NAFLD and in 399 sex- and age-matched healthy people undergoing health checkups. Serum levels of sulfated DHEA (DHEA-S) were measured by chemiluminescent enzyme immunoassay.


RESULTS
Serum DHEA-S levels in NAFLD patients were similar to those in the control group. Of 133 patients, 90 patients were diagnosed as non-alcoholic steatohepatitis (NASH): 73 patients had stage 0-2, and 17 had stage 3 or 4. Patients with advanced NAFLD (NASH with fibrosis stage 3 or 4) had lower plasma levels of DHEA-S than patients with mild NAFLD (simple steatosis or NASH with fibrosis stage 0-2). The area under the receiver operating characteristic curve for DHEA in separating patients with and without advanced fibrosis was 0.788. A "dose effect" of lower DHEA-S and incremental fibrosis stage was observed with a mean DHEA-S of 170.4 ± 129.2, 137.6 ± 110.5, 96.2 ± 79.3, 61.2 ± 46.3 and 30.0 ± 32.0 µg/dL for fibrosis stages 0, 1, 2, 3, and 4, respectively. The association between DHEA-S and severity of NAFLD persisted after adjusting for age, sex and insulin resistance.


CONCLUSIONS
Low circulating DHEA-S might have a role in the development of advanced NASH.
Sumida
Yoshio
Y
Center for Digestive and Liver Diseases, Department of Pathology, Nara City Hospital, Nara.
Yonei
Yoshikazu
Y
Kanemasa
Kazuyuki
K
Hara
Tasuku
T
Inada
Yutaka
Y
Sakai
Kyoko
K
Imai
Shunsuke
S
Hibino
Sawako
S
Yamaguchi
Kanji
K
Mitsuyoshi
Hironori
H
Yasui
Kohichiroh
K
Minami
Masahito
M
Itoh
Yoshito
Y
Naito
Yuji
Y
Yoshikawa
Toshikazu
T
Okanoue
Takeshi
T