Schmidt L E, Ring-Larsen H
Department of Hepatology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
Curr Pharm Des. 2006;12(35):4637-47. doi: 10.2174/138161206779010413.
Hepatorenal syndrome is a severe, but not uncommon complication of decompensated liver cirrhosis. In particular, the rapidly progressive form of hepatorenal syndrome (type 1) is associated with a dismal prognosis. Established hepatorenal syndrome has a spontaneous reversibility below 5%. Hepatorenal syndrome is involved in more than 50% of cirrhosis-related mortality. Thus, any treatment capable of reversing hepatorenal syndrome would be expected to reduce morbidity and mortality from liver cirrhosis. A pathophysiological hallmark of hepatorenal syndrome is arterial underfilling due to an extreme splanchnic vasodilatation. Consequently, potent vasoconstrictors capable of reversing this vasodilatation have been investigated in hepatorenal syndrome. Several vasoconstrictors including the alpha-adrenergic agonists, midodrine and noradrenalin, and the vasopressor analogues, ornipressin and terlipressin, have all been associated with a significant improvement in renal function in 57 to 100% of cases and even reversal of hepatorenal syndrome in 42 to 100% of cases. The majority of recent studies are on terlipressin. A randomized, controlled trial showed a significant effect of terlipressin on reversal of hepatorenal syndrome. The contribution of volume expansion to the beneficial effects of vasoconstrictors on hepatorenal syndrome remains to be determined. In general, reversal of hepatorenal syndrome was associated with an improved survival. However, it remains to be determined if vasoconstrictor therapy should be used in hepatorenal syndrome in general, or if it should be reserved for potential candidates for liver transplantation. In conclusion, evidence for a beneficial effect of vasoconstrictor therapy for the treatment of hepatorenal syndrome is steadily accumulating. Confirmation of the preliminary data in larger randomized, controlled trials looking at long-term survival is required.
肝肾综合征是失代偿期肝硬化严重但并不罕见的并发症。特别是肝肾综合征的快速进展型(1型)预后不佳。已确诊的肝肾综合征自发逆转率低于5%。肝肾综合征导致超过50%的肝硬化相关死亡。因此,任何能够逆转肝肾综合征的治疗方法都有望降低肝硬化的发病率和死亡率。肝肾综合征的一个病理生理特征是由于内脏极度血管扩张导致动脉血容量不足。因此,在肝肾综合征中对能够逆转这种血管扩张的强效血管收缩剂进行了研究。几种血管收缩剂,包括α-肾上腺素能激动剂米多君和去甲肾上腺素,以及血管升压素类似物鸟氨酸加压素和特利加压素,在57%至100%的病例中均与肾功能显著改善相关,甚至在42%至100%的病例中与肝肾综合征的逆转相关。近期大多数研究针对的是特利加压素。一项随机对照试验表明特利加压素对逆转肝肾综合征有显著效果。扩容对血管收缩剂治疗肝肾综合征的有益作用的贡献仍有待确定。一般来说,肝肾综合征的逆转与生存率提高相关。然而,血管收缩剂治疗是否应普遍用于肝肾综合征,还是应仅用于肝移植潜在候选者,仍有待确定。总之,血管收缩剂治疗对肝肾综合征治疗有益作用的证据正在不断积累。需要在更大规模的观察长期生存的随机对照试验中对初步数据进行确认。