Aranha Márcia M, Cortez-Pinto Helena, Costa Adília, da Silva Isabel B Moreira, Camilo Maria E, de Moura Miguel Carneiro, Rodrigues Cecília M P
Centro de Patogénese Molecular, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal.
Eur J Gastroenterol Hepatol. 2008 Jun;20(6):519-25. doi: 10.1097/MEG.0b013e3282f4710a.
BACKGROUND/AIMS: The pathogenesis of steatohepatitis remains largely unknown; however, bile acids may play a role as potential mediators of liver damage. The aim of this study was to characterize bile acid profiles in liver tissue of patients with steatohepatitis.
Bile acid composition was determined by gas-liquid chromatography in liver tissue from patients with nonalcoholic steatohepatitis (NASH; n=15), patients with alcoholic steatohepatitis (ASH; n=14), and controls (n=8). Liver biopsies were graded for steatosis, inflammation, and fibrosis.
Bile acids were moderately increased in liver tissue of steatohepatitis patients compared with controls (P<0.05). Deoxycholic, chenodeoxycholic, and cholic acids were elevated by 92, 64, and 43%, respectively, in patients with steatohepatitis (P<0.05). Cholic acid was the prevailing bile acid in NASH patients and in controls. More hydrophobic bile acid species were elevated in ASH patients compared with controls (P<0.05). Significant correlations were found in NASH patients between hepatic chenodeoxycholic acid and fibrosis, and between cholic acid and trihydroxy/dihydroxy bile acids and inflammation (P<0.05). In patients with ASH, cholic acid and trihydroxy/dihydroxy bile acids were correlated with steatosis (P<0.01).
This study shows a distinct pattern of bile acids in the liver of patients with steatohepatitis. Further, the association between bile acids and histological liver injury suggests an association of specific bile acids and disease progression, possibly through bile acid-induced liver injury.
背景/目的:脂肪性肝炎的发病机制在很大程度上仍不清楚;然而,胆汁酸可能作为肝损伤的潜在介质发挥作用。本研究的目的是描述脂肪性肝炎患者肝组织中的胆汁酸谱。
采用气液色谱法测定非酒精性脂肪性肝炎(NASH;n = 15)、酒精性脂肪性肝炎(ASH;n = 14)患者及对照组(n = 8)肝组织中的胆汁酸组成。对肝活检组织进行脂肪变性、炎症和纤维化分级。
与对照组相比,脂肪性肝炎患者肝组织中的胆汁酸中度升高(P < 0.05)。脂肪性肝炎患者的脱氧胆酸、鹅去氧胆酸和胆酸分别升高了92%、64%和43%(P < 0.05)。胆酸是NASH患者和对照组中主要的胆汁酸。与对照组相比,ASH患者中更多疏水性胆汁酸种类升高(P < 0.05)。在NASH患者中,肝组织中的鹅去氧胆酸与纤维化之间,以及胆酸与三羟基/二羟基胆汁酸和炎症之间存在显著相关性(P < 0.05)。在ASH患者中,胆酸和三羟基/二羟基胆汁酸与脂肪变性相关(P < 0.01)。
本研究显示了脂肪性肝炎患者肝脏中胆汁酸的独特模式。此外,胆汁酸与肝脏组织学损伤之间的关联表明特定胆汁酸与疾病进展有关,可能是通过胆汁酸诱导的肝损伤。