Department of Infectious Diseases, Liver Diseases and Acquired Immune Deficiency, Wroclaw Medical University, Wroclaw, Poland.
Department of Infectious Diseases, Regional Specialistic Hospital in Wroclaw, Wroclaw, Poland.
J Physiol Pharmacol. 2020 Feb;71(1). doi: 10.26402/jpp.2020.1.11. Epub 2020 Jun 13.
Hepatocellular carcinoma (HCC) development is a complex process with well-known risk factors, however the role of betatrophin/angiopoietin-like protein 8 and irisin has been poorly investigated thus far. The aim of this study is to measure betatrophin and irisin serum levels in HCC, cirrhotic patients and controls, assess their relationship with cancer etiology and grade, metabolic abnormalities and liver dysfunction severity. Serum betatrophin and irisin concentrations were measured with commercially available ELISA kits in 69 cirrhotic patients with HCC, 24 patients with non-viral cirrhosis and 20 healthy volunteers. The severity of liver disfunction was assessed according to Child-Pugh (C-P) score, while HCC grade according to the Barcelona clinic liver cancer (BCLC) staging system. Serum betatrophin concentration was significantly higher (33.7 ± 13.4 versus 12.3 ± 2.0 ng/ml; P < 0.001), while serum irisin level significantly lower in HCC patients compared to controls (2.52 ± 1.14 versus 4.46 ± 1.34 μg/ml; P = 0.02). Betatrophin level was also significantly elevated among cirrhotic patients compared to healthy volunteers. More evident serum betatrophin increase was found in patients with viral disease (34.8 ± 12.9 versus 26.1 ± 13.8 ng/ml; P < 0.001). Serum irisin concentration was significantly decreased in more advanced HCC cases (stage A versus C according to BCLC: 3.4 ± 1.3 versus 1.89 ± 1.1 μg/ml; P = 0.02). Decline of serum irisin (A: 3.4 ± 1.2; B: 2.42 ± 0.8; C: 1.91 ± 1.19 μg/ml; P = 0.03) and up-regulation of serum betatrophin levels (A: 24.1 ± 13.8; B: 39.3 ± 11.4; C: 46.2 ± 9.4 ng/ml; P = 0.03) were observed in patients with more advanced cirrhosis according to C-P score. We concluded that betatrophin serum level increased in cirrhotic patients, compared to controls. Since there was no difference between cirrhotic patients with and without intercurrent HCC, we suppose it may have an influence on fibrosis development, however not hepatocarcinogensis. Irisin serum level decreased in HCC patients, especially with more advanced disease grade, and was inversely related to the severity of liver disfunction.
肝细胞癌 (HCC) 的发展是一个复杂的过程，其具有众所周知的风险因素，然而，β细胞素/血管生成素样蛋白 8 和鸢尾素的作用迄今为止研究甚少。本研究的目的是测量 HCC、肝硬化患者和对照者的血清β细胞素和鸢尾素水平，评估它们与癌症病因和分级、代谢异常和肝功能严重程度的关系。使用商业上可获得的 ELISA 试剂盒测量 69 例 HCC 肝硬化患者、24 例非病毒性肝硬化患者和 20 例健康志愿者的血清β细胞素和鸢尾素浓度。根据 Child-Pugh (C-P) 评分评估肝功能严重程度，根据巴塞罗那临床肝癌 (BCLC) 分期系统评估 HCC 分级。与对照组相比，HCC 患者的血清β细胞素浓度显著升高 (33.7 ± 13.4 与 12.3 ± 2.0 ng/ml；P < 0.001)，而血清鸢尾素水平显著降低 (2.52 ± 1.14 与 4.46 ± 1.34 μg/ml；P = 0.02)。与健康志愿者相比，肝硬化患者的血清β细胞素水平也显著升高。与健康志愿者相比，病毒性疾病患者的血清β细胞素升高更为明显 (34.8 ± 12.9 与 26.1 ± 13.8 ng/ml；P < 0.001)。根据 BCLC，更晚期 HCC 病例的血清鸢尾素浓度显著降低 (根据 BCLC，A 期与 C 期：3.4 ± 1.3 与 1.89 ± 1.1 μg/ml；P = 0.02)。根据 C-P 评分，随着肝功能恶化，血清鸢尾素水平下降 (A：3.4 ± 1.2；B：2.42 ± 0.8；C：1.91 ± 1.19 μg/ml；P = 0.03)，血清β细胞素水平升高 (A：24.1 ± 13.8；B：39.3 ± 11.4；C：46.2 ± 9.4 ng/ml；P = 0.03)，在 C-P 评分较高的肝硬化患者中观察到。我们得出结论，与对照组相比，肝硬化患者的血清β细胞素水平升高。由于在伴有或不伴有 HCC 的肝硬化患者之间没有差异，我们推测它可能对纤维化的发展有影响，但对肝癌的发生没有影响。HCC 患者的血清鸢尾素水平降低，尤其是疾病分级较高的患者，且与肝功能严重程度呈负相关。
