Tietge Uwe J F, Bahr Matthias J, Manns Michael P, Böker Klaus H W
Department of Gastroenterology and Hepatology, Hanover Medical School, Carl-Neuberg-Strasse 1, 30623 Hanover, Germany.
Transpl Int. 2003 Jan;16(1):1-8. doi: 10.1007/s00147-002-0484-z. Epub 2002 Dec 10.
The aim of this study was to investigate the impact of orthotopic liver transplantation (OLT) on plasma levels and splanchnic turnover of key amino acids for muscular (branched-chain amino acids: BCAAs) and hepatic metabolism (aromatic amino acids (AAAs) and methionine) in 48 patients with cirrhosis, 14 patients after OLT, and 46 controls. Also, hepatic amino-acid supply and resting energy expenditure were measured. BCAA levels (no hepatic uptake) decreased in cirrhosis (P<0.001) and were improved, although not normalized, after OLT (P<0.001). AAA and methionine levels were raised in cirrhosis (P<0.001) and normalized after OLT (P<0.001). Hepatic supply of these amino acids increased in patients graded Child B and C and decreased significantly after OLT. Splanchnic uptake of AAAs and methionine increased significantly in Child-B and decreased in Child-C patients. After OLT, splanchnic extraction of AAAs and methionine was as in Child A. Circulating AAAs and methionine correlated with indocyanine-green half-life (r=0.71, P<0.001) and resting energy expenditure (r=0.50, P<0.001), indicating that levels of circulating AAAs and methionine in cirrhosis are determined by hepatic and extra-hepatic metabolic factors. This study demonstrates persistent changes in muscular metabolism of BCAAs after OLT, while the hepatic amino-acid metabolism is normalized due to (1) a significant reduction in the rate of peripheral proteolysis, and (2) improved liver function compared with that in patients with cirrhosis.
本研究旨在调查原位肝移植(OLT)对48例肝硬化患者、14例OLT术后患者及46例对照者血浆中肌肉代谢关键氨基酸(支链氨基酸:BCAAs)和肝脏代谢关键氨基酸(芳香族氨基酸(AAAs)和蛋氨酸)水平及内脏周转率的影响。此外,还测量了肝脏氨基酸供应和静息能量消耗。肝硬化患者BCAA水平(无肝脏摄取)降低(P<0.001),OLT术后虽未恢复正常,但有所改善(P<0.001)。肝硬化患者AAA和蛋氨酸水平升高(P<0.001),OLT术后恢复正常(P<0.001)。Child B级和C级患者肝脏对这些氨基酸的供应增加,OLT术后显著减少。Child-B患者内脏对AAA和蛋氨酸的摄取显著增加,Child-C患者则减少。OLT术后,AAA和蛋氨酸的内脏提取情况与Child A级患者相同。循环中的AAA和蛋氨酸与吲哚菁绿半衰期(r=0.71,P<0.001)和静息能量消耗(r=0.50,P<0.001)相关,表明肝硬化患者循环中AAA和蛋氨酸的水平由肝脏和肝外代谢因素决定。本研究表明,OLT术后BCAAs的肌肉代谢持续变化,而肝脏氨基酸代谢恢复正常,原因是(1)外周蛋白水解率显著降低,(2)与肝硬化患者相比肝功能改善。