High-sensitivity C-reactive protein is an independent clinical feature of nonalcoholic steatohepatitis (NASH) and also of the severity of fibrosis in NASH

J Gastroenterol. 2007 Jul;42(7):573-82. doi: 10.1007/s00535-007-2060-x. Epub 2007 Jul 25.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / metabolism
  • C-Reactive Protein / metabolism*
  • Fatty Liver / blood*
  • Fatty Liver / classification
  • Fatty Liver / diagnosis
  • Fatty Liver / pathology*
  • Female
  • Gene Expression
  • Hepatitis / diagnosis
  • Hepatitis / physiopathology*
  • Humans
  • Interleukin-6 / metabolism
  • Liver / physiopathology
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / classification
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / pathology*
  • Logistic Models
  • Male
  • Middle Aged
  • Prospective Studies
  • RNA, Messenger
  • Reverse Transcriptase Polymerase Chain Reaction
  • Severity of Illness Index


  • Biomarkers
  • Interleukin-6
  • RNA, Messenger
  • C-Reactive Protein