Holt R I, Baker A J, Jones J S, Miell J P
Department of Medicine, King's College School of Medicine and Dentistry, London, UK.
Pediatr Transplant. 1998 Feb;2(1):76-84.
Over 50% of children with established cirrhosis have evidence of growth failure and malnutrition. Orthotopic liver transplantation (OLT) is a successful treatment for many children and leads to improved growth and nutrition. Most of the anabolic actions of GH are mediated through the generation of the mitogenic polypeptide insulin-like growth factor-I (IGF-I). Although this is synthesised ubiquitously, the bulk of circulating IGF-I is derived from the liver. The actions of IGF-I are modulated by a family of at least six high-affinity binding proteins (IGFBPs). Growth failure in end-stage liver disease, both before and after OLT, may result from abnormalities in the IGF-IGFBP axis. Children who had undergone successful OLT were studied before and after OLT. Anthropometry was measured by standard techniques. Serum IGFs, IGFBPs and acid labile subunit (ALS) were measured by RIA, IRMA, ELISA, Western ligand and immunoblotting. The most severely affected anthropometric parameters were skin fold thickness and mid-arm circumference. After OLT there was a marked improvement in these parameters. Chronic liver disease was characterised by low serum IGF-I, IGF-II, IGFBP-3 and ALS levels with raised IGFBP-1 and -2 levels. Serum IGFBP-1 and -2 were negatively correlated with pre-OLT anthropometric parameters. After OLT, there was a rapid normalisation of serum IGF-I, while IGF-II and IGFBP-3 overshot to supranormal levels. ALS levels post-OLT remained below control levels. By 3 years post-OLT, IGFBP-3 had fallen to levels which were insignificantly different from controls. IGFBP-1 fell but remained above normal, while there was no significant change in IGFBP-2. Growth post-OLT correlated positively with serum IGF-I and negatively with IGFBP-1. In conclusion, chronic liver disease is associated with marked changes in body composition. These changes are associated with and may be caused by an impaired generation of IGF-I and altered production of IGFBPs. After OLT there is a marked improvement in growth associated with partial normalisation of the IGF-IGFBP axis. However, there are persistent abnormalities in this axis which may explain growth failure post-OLT.
超过50%的已确诊肝硬化儿童有生长发育迟缓及营养不良的迹象。原位肝移植（OLT）对许多儿童来说是一种成功的治疗方法，可促进生长并改善营养状况。生长激素（GH）的大多数合成代谢作用是通过有丝分裂原性多肽胰岛素样生长因子-I（IGF-I）的生成来介导的。虽然IGF-I在全身各处都有合成，但循环中的IGF-I大部分来自肝脏。IGF-I的作用受到至少六种高亲和力结合蛋白（IGFBPs）家族的调节。终末期肝病患者在OLT前后出现的生长发育迟缓可能是由IGF-IGFBP轴异常所致。对成功接受OLT的儿童在OLT前后进行了研究。采用标准技术测量人体测量学指标。通过放射免疫分析（RIA）、免疫放射分析（IRMA）、酶联免疫吸附测定（ELISA）、Western配体印迹法和免疫印迹法测量血清IGF、IGFBP和酸不稳定亚基（ALS）。受影响最严重的人体测量学参数是皮褶厚度和上臂围。OLT后这些参数有显著改善。慢性肝病的特征是血清IGF-I、IGF-II、IGFBP-3和ALS水平降低，而IGFBP-1和-2水平升高。血清IGFBP-1和-2与OLT前人体测量学参数呈负相关。OLT后，血清IGF-I迅速恢复正常，而IGF-II和IGFBP-3则超过正常水平。OLT后ALS水平仍低于对照水平。OLT后3年，IGFBP-3降至与对照组无显著差异的水平。IGFBP-1下降但仍高于正常水平，而IGFBP-2无显著变化。OLT后的生长与血清IGF-I呈正相关，与IGFBP-1呈负相关。总之，慢性肝病与身体成分的显著变化有关。这些变化与IGF-I生成受损和IGFBPs产生改变有关，且可能由其引起。OLT后生长有显著改善，与IGF-IGFBP轴部分恢复正常有关。然而，该轴仍存在持续异常，这可能解释了OLT后的生长发育迟缓。
