Yoshikawa Kyoko, Iwasa Motoh, Eguchi Akiko, Kojima Shinichi, Yoshizawa Naohiko, Tempaku Mina, Sugimoto Ryosuke, Yamamoto Norihiko, Sugimoto Kazushi, Kobayashi Yoshinao, Hasegawa Hiroshi, Takei Yoshiyuki
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Mie University, Mie, Japan.
Hepatol Commun. 2017 Oct 16;1(9):946-956. doi: 10.1002/hep4.1109. eCollection 2017 Nov.
Chronic liver disease patients often have complications, such as hepatocellular carcinoma (HCC) and acute bacterial infection. Model for end-stage liver disease and Child-Pugh scores are useful prognostic factors for chronic liver diseases but not for all chronic conditions, such as HCC. Our investigative aim targeted the prognostic abilities of neutrophil gelatinase-associated lipocalin (NGAL) in rat and human chronic liver diseases. Blood NGAL levels were measured by enzyme-linked immunosorbent assay in rats with cirrhosis and 96 patients with chronic liver disease and HCC. We examined the correlation between blood NGAL levels and liver functions as well as survival. In our rat model, liver NGAL expression was assessed by immunostaining, real-time quantitative polymerase chain reaction, and immunoblot. In rats with cirrhosis, blood NGAL levels were continuously and significantly elevated in the deceased group and were significantly correlated with liver functions. Liver NGAL, toll-like receptor 4, and interleukin-6 levels were increased in the deceased group compared to the survival group. Blood NGAL levels were significantly correlated with liver NGAL levels, indicating blood NGAL was derived from the liver. In patients with chronic liver disease, blood NGAL levels were associated with liver function and renal function. Blood NGAL levels were significantly increased in patients with chronic liver disease with HCC compared to without HCC. For the survival group, 38 out of 96 patients were dead in the average follow-up period of 9.9 months. The patients with blood NGAL ≤119 ng/mL had significantly longer rates of survival compared to patients with blood NGAL >119 ng/mL. : Blood NGAL predicts the survival rate in rat and human chronic liver diseases. Our findings suggest blood NGAL may be prognostic of survival in chronic liver diseases complicated by HCC. ( 2017;1:946-956).
慢性肝病患者常伴有并发症,如肝细胞癌(HCC)和急性细菌感染。终末期肝病模型和Child-Pugh评分是慢性肝病有用的预后因素,但并非适用于所有慢性疾病,如HCC。我们的研究目的是针对中性粒细胞明胶酶相关脂质运载蛋白(NGAL)在大鼠和人类慢性肝病中的预后能力。通过酶联免疫吸附测定法测量了肝硬化大鼠和96例慢性肝病及HCC患者的血液NGAL水平。我们检测了血液NGAL水平与肝功能以及生存率之间的相关性。在我们的大鼠模型中,通过免疫染色、实时定量聚合酶链反应和免疫印迹评估肝脏NGAL表达。在肝硬化大鼠中,死亡组的血液NGAL水平持续且显著升高,并与肝功能显著相关。与存活组相比,死亡组的肝脏NGAL、Toll样受体4和白细胞介素-6水平升高。血液NGAL水平与肝脏NGAL水平显著相关,表明血液NGAL来源于肝脏。在慢性肝病患者中,血液NGAL水平与肝功能和肾功能相关。与无HCC的慢性肝病患者相比,伴有HCC的慢性肝病患者的血液NGAL水平显著升高。在96例患者的存活组中,平均随访9.9个月期间有38例死亡。血液NGAL≤119 ng/mL的患者与血液NGAL>119 ng/mL的患者相比,生存率显著更长。:血液NGAL可预测大鼠和人类慢性肝病患者的生存率。我们的研究结果表明,血液NGAL可能是伴有HCC的慢性肝病患者生存的预后指标。(2017;1:946 - 956)