肝硬化门脉高压症急症与择期手术治疗的病理比较及门脉高压症机制的探讨

An inquiry into mechanism of portal hypertension through comparative analysis of 150 cases of cirrhosis and portal hypertension undergoing emergent or elective surgical intervention

目的比较研究肝硬化门脉高压症(PTH)急症与择期贲门周围血管离断术(EED)治疗患者围术期肝功能、并发症及肝脏病理改变的差异,并探讨肝硬化PTH肝内微循环改变的细胞生物学机制。方法128例临床病理资料完整的肝硬化PTH行EED病例,其中28例因食管胃贲门、底部静脉破裂大出血行急症EED,100例作择期EED治疗。对急症组与择期组的围术期肝功能、影像学资料、术中活检肝组织病理改变作比较。采用免疫组织化学方法检测肝组织中肝星状细胞(HSC)表达α平滑肌肌动蛋白(αSMA)、微管蛋白α、β以及肝组织内皮素1(ET1)的表达变化与肝硬化PTH间的关系。结果急症EED组术前(1周内)门静脉内径和大出血率及术后围术期并发症发生率明显高于择期EED组(分别P<0.05,P<0.01),而术后4周肝功能指标比较,除急症EED组ALT、AST高于择期EED组外,两组间白蛋白、球蛋白、总胆红素等指标无明显差异;急症EED组85.7%为活动期肝硬化,明显高于择期EED组的21.00%(P<0.01),两组肝组织内均存在门静脉分支及窦周纤维化,肝动脉及门静脉不同程度弹力纤维断裂,血管基底膜非均匀性增厚;与正常对照及CHB肝组织比较,两组肝组织内αSMA强阳性HSC数量均明显增多,HSC及部分肝细胞内微管蛋白α和微管蛋白β表达明显上调,ET1主要见于HSC。

Objective Liver function in perioperative periods, postoperative complications, and pathological changes in the liver were studied and compared between patients undergoing emergent and elective surgical intervention (extensive esophagogastric devascularization, EED) for portal hypertension (PTH), with the purpose to elucidate the pathogenesis of PTH. Methods The clinical data and liver biopsies from 150 cases of inpatients with hepatis cirrhosis and PTH who underwent either emergent (28 cases) or elective (100 cases) surgical intervention including extensive esophagogastric devascularization (EED) in 302 th Hospital of PLA were analysed. Liver biopsy was done in 128 patients, and the expression of α-smooth muscle actin (α-SMA), tubulinαand βin hepatic stellate cells (HSCs), and endothelin-1 (ET-1) was histochemically studied in the liver tissue. Results It was found that the mean internal diameter of portal veins before surgery was larger and the incidence of pre-operative acute variceal haemorrhage was significantly higher in the emergent EED group than those in the elective EED group (P<0.05, P<0.01, respectively). In respect to liver function, the elevated serum ALT, AST and TBil in the emergent EED group lowered relatively slower after the operation compared with the elective group, while there was no significant difference in regard to serum Alb levels between two groups. 85.7% of patients undergoing emergent operation showed pathology of active liver cirrhosis, which was obviously higher compared with 21.00% in elective EED group (P<0.01). Periportal and perisinusoid fibrosis, the formation of basement membranes beneath the hepatic sinusoidal endothelial cells (ECs), fragmentation of elastic fiber, and uneven thickening of base membranes in portal venules and hepatic arteries were found in all liver biopsies. The expression of α-SMA, tubulin α and β was found up-regulated in HSCs in the cirrhotic liver tissue from both groups. The unevenly increased ET-1 was localized mainly in α-SMA positive-HSCs and Ecs, and to a lesser extent in hepatocytes. Conclusions Our data suggest that higher portal pressure and active liver cirrhosis are predominant predisposing factors of acute gastroesophageal varicose haemorrhage, which is the main indication for emergent surgical intervention for the patients with liver cirrhosis complicated by PTH. The prevention and treatment of postoperative complications and measures to improve liver function should be emphasized. The up-regulated expression of α-SMA, tubulin α,β and ET-1 in activated HSCs, as well as Ecs, contributing to an increase in contractions of hepatic sinusoids and terminal vessels, may be one of main cytobiological bases of mechanism of sustained PTH in hepatic cirrhosis.