Yoneda Masato, Mawatari Hironori, Fujita Koji, Iida Hiroshi, Yonemitsu Kyoko, Kato Shingo, Takahashi Hirokazu, Kirikoshi Hiroyuki, Inamori Masahiko, Nozaki Yuichi, Abe Yasunobu, Kubota Kensuke, Saito Satoru, Iwasaki Tomoyuki, Terauchi Yasuo, Togo Shinji, Maeyama Shiro, Nakajima Atsushi
Division of Gastroenterology, Yokohama City University Hospital, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan.
J Gastroenterol. 2007 Jul;42(7):573-82. doi: 10.1007/s00535-007-2060-x. Epub 2007 Jul 25.
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.
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.
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).
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.
非酒精性脂肪性肝病(NAFLD)的变化范围广泛,从脂肪变性到脂肪性肝炎(NASH)。然而,通过临床检查区分NASH和非进展性NAFLD仍然很困难。我们研究了血清高敏C反应蛋白(hs-CRP)与NASH的发病机制和进展之间的相互关系。
对100例经组织学证实的NAFLD患者(29例脂肪变性患者和71例NASH患者)测量hs-CRP,并进行实时逆转录聚合酶链反应(RT-PCR)分析,以测量肝脏内CRP和白细胞介素(IL)-6的mRNA表达。
多元回归分析结果显示,与脂肪变性病例相比,NASH病例中的hs-CRP显著升高(P = 0.0048)。此外,在NASH患者中,与轻度纤维化患者相比,重度纤维化患者的hs-CRP显著升高(P = 0.0384),即使在对年龄、性别、糖尿病的存在、体重指数、内脏脂肪面积、皮下脂肪面积、胰岛素抵抗的稳态模型评估、高密度脂蛋白胆固醇、甘油三酯和低密度脂蛋白胆固醇进行调整之后也是如此。RT-PCR分析结果显示,与脂肪变性患者相比,NASH患者肝脏内CRP的mRNA表达增加,但IL-6的mRNA表达未增加(P = 0.0228)。
这是第一份证明与单纯非进展性脂肪变性病例相比,NASH病例中hs-CRP持续且显著升高的报告。我们的结果表明,hs-CRP可能是一种临床特征,不仅可以将NASH与单纯非进展性脂肪变性区分开来,还可以表明NASH病例中肝纤维化的严重程度。