Bile acid levels are increased in the liver of patients with steatohepatitis

被引:179
作者
Aranha, Marcia M. [1 ]
Cortez-Pinto, Helena [2 ,3 ]
Costa, Adilia [4 ]
da Silva, Isabel B. Moreira [1 ]
Camilo, Maria E. [2 ]
de Moura, Miguel Carneiro [3 ]
Rodrigues, Cecilia M. P. [1 ]
机构
[1] Univ Lisbon, Fac Pharm, Ctr Patogenese Mol, P-1600083 Lisbon, Portugal
[2] Univ Lisbon, Unidade Nutr & Metab, Inst Mol Med, P-1600083 Lisbon, Portugal
[3] Univ Lisbon, Hosp Santa Maria, Dept Gastroenterol, P-1600083 Lisbon, Portugal
[4] Hosp Santa Maria, Dept Pathol, Lisbon, Portugal
关键词
alcoholic and nonalcoholic steatohepatitis; bile acids; fibrosis; inflammation; liver injury;
D O I
10.1097/MEG.0b013e3282f4710a
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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. Methods 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. Results 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). Conclusion 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.
引用
收藏
页码:519 / 525
页数:7
相关论文
共 37 条
[1]  
AKASHI Y, 1983, CLIN CHIM ACTA, V133, P125
[2]  
ALME B, 1977, J LIPID RES, V18, P339
[3]   SEPARATION AND COMPUTERIZED GAS CHROMATOGRAPHY MASS SPECTROMETRY OF UNCONJUGATED NEUTRAL STEROIDS IN PLASMA [J].
AXELSON, M ;
SJOVALL, J .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1974, 5 (08) :733-738
[4]  
BLAU K, 1978, HDB DERIVATES CHROMA
[5]  
BOTLA R, 1995, J PHARMACOL EXP THER, V272, P930
[6]   Cathepsin B inactivation attenuates hepatic injury and fibrosis during cholestasis [J].
Canbay, A ;
Guicciardi, ME ;
Higuchi, H ;
Feldstein, A ;
Bronk, SF ;
Rydzewski, R ;
Taniai, M ;
Gores, GJ .
JOURNAL OF CLINICAL INVESTIGATION, 2003, 112 (02) :152-159
[7]   Toxic bile salts induce rodent hepatocyte apoptosis via direct activation of Fas [J].
Faubion, WA ;
Guicciardi, ME ;
Miyoshi, H ;
Bronk, SF ;
Roberts, PJ ;
Svingen, PA ;
Kaufmann, SH ;
Gores, GJ .
JOURNAL OF CLINICAL INVESTIGATION, 1999, 103 (01) :137-145
[8]   Free fatty acids promote hepatic lipotoxicity by stimulating TNF-α expression via a lysosomal pathway [J].
Feldstein, AE ;
Werneburg, NW ;
Canbay, A ;
Guicciardi, ME ;
Bronk, SF ;
Rydzewski, R ;
Burgart, LJ ;
Gores, GJ .
HEPATOLOGY, 2004, 40 (01) :185-194
[9]   Hepatocyte apoptosis and Fas expression are prominent features of human nonalcoholic steatohepatitis [J].
Feldstein, AE ;
Canbay, A ;
Angulo, P ;
Taniai, M ;
Burgart, LJ ;
Lindor, KD ;
Gores, GJ .
GASTROENTEROLOGY, 2003, 125 (02) :437-443
[10]   Hepatic levels of bile acids in end-stage chronic cholestatic liver disease [J].
Fischer, S ;
Beuers, U ;
Spengler, U ;
Zwiebel, FM ;
Koebe, HG .
CLINICA CHIMICA ACTA, 1996, 251 (02) :173-186