Mazziotti Gherardo, Sorvillo Francesca, Morisco Filomena, Carbone Antonella, Rotondi Mario, Stornaiuolo Gianfranca, Precone Davide F, Cioffi Michele, Gaeta Giovanni B, Caporaso Nicola, Carella Carlo
Department of Clinical and Experimental Medicine F. Magrassi, Second University of Naples, Naples, Italy.
Cancer. 2002 Dec 15;95(12):2539-45. doi: 10.1002/cncr.11002.
BACKGROUND: Although experimental studies have demonstrated an important role of insulin-like growth factor I (IGF-I) in hepatocarcinogenesis, the clinical data about IGF-I in patients with hepatocellular carcinoma (HCC) are scarce and controversial. To the authors' knowledge, this is the first prospective study investigating the longitudinal correlation between modifications in serum IGF-I levels and the development of HCC in a cohort of patients with hepatitis C virus (HCV)-related cirrhosis. METHODS: One hundred fourteen consecutive patients with HCV-related Child Grade A cirrhosis were followed prospectively at the Second University of Naples for 56.4 +/- 12.0 months with ultrasound examinations of the liver and serum alpha-fetoprotein determination every 6 months. At each clinical evaluation, the severity of disease was graded according to the established Child-Pugh scoring system. Serum IGF-I levels were measured prospectively at the study entry and at least every 12 months throughout follow-up. RESULTS: Twenty patients (19.2%) developed HCC during follow-up. Eleven of these patients had persistent Child Grade A cirrhosis for the whole study, whereas the other 9 patients developed HCC after their cirrhosis progressed from Child Grade A to Grade B. In patients who remained free of HCC for the whole study, serum IGF-I concentrations did not modify significantly during follow-up. Conversely, in patients who developed HCC, IGF-I levels decreased significantly during follow-up (from 72.6 +/- 29.9 microg/L to 33.8 +/- 14.5 microg/L; P = 0.001). In these patients, the significant decrease occurred both in patients with persistent Child Grade A cirrhosis and in patients with cirrhosis that progressed from Child Grade A to Grade B. The reduction in IGF-I level preceded the diagnosis of HCC by 9.3 +/- 3.1 months. CONCLUSIONS: This prospective study demonstrates that, in patients with HCV-related cirrhosis, 1) the development of HCC is accompanied by a significant reduction of serum IGF-I levels independent of the grade of impairment of liver function; and 2) modification of the IGF-I level precedes the morphologic appearance of HCC, permitting a precocious diagnosis of the tumor.
背景：尽管实验研究已证明胰岛素样生长因子I（IGF-I）在肝癌发生过程中起重要作用，但关于肝细胞癌（HCC）患者中IGF-I的临床数据却很少且存在争议。据作者所知，这是第一项前瞻性研究，旨在调查丙型肝炎病毒（HCV）相关肝硬化患者队列中血清IGF-I水平变化与HCC发生之间的纵向相关性。 方法：那不勒斯第二大学对114例连续的HCV相关Child A级肝硬化患者进行前瞻性随访，为期56.4±12.0个月，每6个月进行一次肝脏超声检查和血清甲胎蛋白测定。每次临床评估时，根据既定的Child-Pugh评分系统对疾病严重程度进行分级。在研究开始时及整个随访过程中至少每12个月前瞻性地测量血清IGF-I水平。 结果：20例患者（19.2%）在随访期间发生了HCC。其中11例患者在整个研究过程中持续为Child A级肝硬化，而另外9例患者在肝硬化从Child A级进展为B级后发生了HCC。在整个研究过程中未发生HCC的患者中，随访期间血清IGF-I浓度无明显变化。相反，在发生HCC的患者中，随访期间IGF-I水平显著下降（从72.6±29.9μg/L降至33.8±14.5μg/L；P = 0.001）。在这些患者中，持续为Child A级肝硬化的患者以及肝硬化从Child A级进展为B级的患者中均出现了显著下降。IGF-I水平下降比HCC诊断提前9.3±3.1个月。 结论：这项前瞻性研究表明，在HCV相关肝硬化患者中，1）HCC的发生伴随着血清IGF-I水平的显著降低，且与肝功能损害程度无关；2）IGF-I水平的变化先于HCC的形态学出现，从而能够对肿瘤进行早期诊断。
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