Nikkilä Katriina, Nissinen Markku J, Gylling Helena, Isoniemi Helena, Miettinen Tatu A
Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Helsinki, Finland.
J Hepatol. 2008 Dec;49(6):936-45. doi: 10.1016/j.jhep.2008.07.026. Epub 2008 Sep 26.
BACKGROUND/AIMS: Liver diseases modify sterol metabolism. Liver transplantation (LTX) provides a model to evaluate the impact of disease-affected liver on sterol metabolism.
We studied serum sterol profiles and their relationships to other biochemical markers in consecutive cholestatic patients with acute liver failure (ALF, n=39) and end-stage primary biliary cirrhosis (PBC, n=67) before and 27d after LTX. Accordingly, we determined serum levels of sterols, bilirubin and prealbumin.
Due to weak cholesterol synthesis of ALF-patients before LTX, their serum levels of cholesterol, lathosterol/cholesterol, cholestanol/cholesterol and lathosterol/campesterol were 18%-41% lower (P<0.05 for each) than in PBC, but ratios of phytosterols to cholesterol were equal. In general, non-cholesterol sterol ratios reflected bilirubin and prealbumin concentrations. Interrelation of surrogate sterols showed that homeostasis of cholesterol metabolism prevailed in lowest cholestanol tertile of ALF-patients consistently, but not in PBC. After LTX, cholesterol levels and lathosterol ratios increased in both groups and phytosterol ratios decreased (P<0.01). Cholestanol decreased profoundly in PBC, but remained 26% higher than in ALF (P<0.05).
Homeostasis of cholesterol metabolism was maintained only in ALF. Metabolism of phytosterols was equal in study groups. PBC- and ALF-patients have differential patterns in their serum sterols and cholesterol metabolism.
背景/目的:肝脏疾病会改变甾醇代谢。肝移植(LTX)提供了一个模型来评估患病肝脏对甾醇代谢的影响。
我们研究了连续的急性肝衰竭(ALF,n = 39)和终末期原发性胆汁性肝硬化(PBC,n = 67)胆汁淤积患者在LTX术前及术后27天的血清甾醇谱及其与其他生化标志物的关系。相应地,我们测定了血清甾醇、胆红素和前白蛋白水平。
由于LTX术前ALF患者胆固醇合成能力较弱,其血清胆固醇、羊毛甾醇/胆固醇、胆甾烷醇/胆固醇和羊毛甾醇/菜油甾醇水平比PBC患者低18% - 41%(每项P < 0.05),但植物甾醇与胆固醇的比值相等。总体而言,非胆固醇甾醇比值反映了胆红素和前白蛋白浓度。替代甾醇的相互关系表明,ALF患者胆甾烷醇三分位数最低时胆固醇代谢稳态持续存在,但PBC患者并非如此。LTX术后,两组患者的胆固醇水平和羊毛甾醇比值均升高,植物甾醇比值降低(P < 0.01)。PBC患者的胆甾烷醇显著降低,但仍比ALF患者高26%(P < 0.05)。
仅在ALF中维持了胆固醇代谢稳态。研究组中植物甾醇的代谢情况相同。PBC和ALF患者的血清甾醇和胆固醇代谢模式不同。