High-sensitivity C-reactive protein is an independent clinical feature of nonalcoholic steatohepatitis (NASH) and also of the severity of fibrosis in NASH.
BACKGROUND
The changes in nonalcoholic fatty liver disease (NAFLD) range over a wide spectrum, extending from steatosis to steatohepatitis (NASH). However, it has remained difficult to differentiate between NASH and nonprogressive NAFLD by clinical examination. We investigated the interrelationships between serum high-sensitivity C-reactive protein (hs-CRP) and the pathogenesis and progression of NASH.


METHODS
Hs-CRP was measured in 100 patients with histologically verified NAFLD (29 with steatosis and 71 with NASH), and a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was performed to measure the intrahepatic mRNA expressions of CRP and interleukin (IL)-6.


RESULTS
The results of a multiple regression analysis revealed that in comparison with cases of steatosis, hs-CRP was significantly elevated (P = 0.0048) in cases of NASH. Furthermore, among patients with NASH, hs-CRP was significantly elevated in those with advanced fibrosis compared with that in those with mild fibrosis (P = 0.0384), even after adjustment for age, sex, presence of diabetes, body mass index, visceral fat area, subcutaneous fat area, homeostasis model assessment for insulin resistance, high-density lipoprotein cholesterol, triglyceride, and low-density lipoprotein cholesterol. The results of the RT-PCR analysis showed that intrahepatic mRNA expression of CRP, but not IL-6, was increased in patients with NASH compared with those with steatosis (P = 0.0228).


CONCLUSIONS
This is the first report to demonstrate consistent and profound elevation of hs-CRP in cases of NASH compared with in cases of simple nonprogressive steatosis. Our results suggest that hs-CRP may be a clinical feature that not only distinguishes NASH from simple nonprogressive steatosis but also indicates the severity of hepatic fibrosis in cases of NASH.
Yoneda
Masato
M
Division of Gastroenterology, Yokohama City University Hospital, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan.
Mawatari
Hironori
H
Fujita
Koji
K
Iida
Hiroshi
H
Yonemitsu
Kyoko
K
Kato
Shingo
S
Takahashi
Hirokazu
H
Kirikoshi
Hiroyuki
H
Inamori
Masahiko
M
Nozaki
Yuichi
Y
Abe
Yasunobu
Y
Kubota
Kensuke
K
Saito
Satoru
S
Iwasaki
Tomoyuki
T
Terauchi
Yasuo
Y
Togo
Shinji
S
Maeyama
Shiro
S
Nakajima
Atsushi
A
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism*; D005234:Fatty Liver / Q000097:blood* / Q000145:classification / Q000175:diagnosis / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D006505:Hepatitis / Q000175:diagnosis / Q000503:physiopathology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000097:blood / Q000145:classification / Q000175:diagnosis / Q000473:pathology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index
D015415:Biomarkers; D015850:Interleukin-6; D012333:RNA, Messenger; D002097:C-Reactive Protein