title: High-sensitivity C-reactive protein is an independent clinical feature of nonalcoholic steatohepatitis (NASH) and also of the severity of fibrosis in NASH.
abstract: 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.
authors.affiliation: Division of Gastroenterology, Yokohama City University Hospital, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Yoneda
authors.forename: Hironori
authors.initials: H
authors.lastname: Mawatari
authors.forename: Koji
authors.initials: K
authors.lastname: Fujita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iida
authors.forename: Kyoko
authors.initials: K
authors.lastname: Yonemitsu
authors.forename: Shingo
authors.initials: S
authors.lastname: Kato
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Takahashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kirikoshi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Inamori
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Nozaki
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Abe
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kubota
authors.forename: Satoru
authors.initials: S
authors.lastname: Saito
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Iwasaki
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Terauchi
authors.forename: Shinji
authors.initials: S
authors.lastname: Togo
authors.forename: Shiro
authors.initials: S
authors.lastname: Maeyama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakajima
mesh_terms: 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
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D012333:RNA, Messenger; D002097:C-Reactive Protein