16例吡咯烷生物碱相关肝窦阻塞综合征的临床病理分析

目的观察吡咯烷生物碱(PA)植物致肝窦阻塞综合征(HSOS)患者的肝穿刺活体组织检查(简称活检)病理学表现。方法选取2012年至2017年诊断为PA-HSOS患者,收集患者一般情况、肝功能指标、服药史、肝穿刺活检时间、肝穿刺病理组织切片、起病6个月后的临床预后等资料。用临床资料进行临床分期;观察不同临床分期患者的病理组织学表现。对数据采用Wilcoxin符号秩和检验、非配对t检验、一元线性回归分析。结果收集到16例患者,起病、随访6个月后丙氨酸转氨酶水平分别为59.25 U/L和25.50 U/L、天冬氨酸转氨酶分别为108 U/L和45 U/L,差异均有统计学意义。而总胆汁酸分别为35μmol/L和36.15μmol/L,白蛋白分别为32.45 g/L和31 g/L,差异无统计学意义。将PA-HSOS病理发展过程分为早期、中期、晚期。早期小叶中心带窦内皮完整性受损,红细胞进入窦内皮与肝细胞之间的窦周间隙。中期出血带内红细胞溶解,网状纤维塌陷密集,胶原纤维沉积,尚有血流的腔隙充血扩张,其腔内覆有窦内皮细胞;出血带周围肝板出现再生现象,部分肝窦代偿性扩张。晚期出血带内胶原沉积形成大面积纤维瘢痕,其内多数有血流的扩张腔隙内覆血管内皮;边缘带肝细胞呈双排再生,插入纤维间隔。肝穿刺组织内重度出血损伤的肝小叶比例和患者预后无关。结论PA-HSOS早期小叶中心带红细胞通过受损的窦内皮进入窦周间隙,表现为肝板出血性坏死。至中晚期出现肝板再生和血管改造,故大部分患者临床病程呈自限性。病理分期和肝穿刺活检时间具有明显相关性,但无法根据标本出血损伤程度判断患者预后。

Clinicopathological analysis of 16 cases of pyrrolizidine alkaloids-associated hepatic sinusoidal obstruction syndrome

Objective To observe the histopathological manifestations of liver biopsy in patients with hepatic sinusoidal obstruction syndrome(HSOS)induced by pyrrolizidine alkaloid(PA).Methods Patients diagnosed with PA-HSOS from 2012 to 2017 were selected,and the general conditions,liver function indexes,medication history,liver biopsy time,histopathological slides of liver biopsy,and follow-up data of clinical prognosis after 6 months of onset were collected.Clinical staging with clinical data was used to observe the histopathological manifestations of patients at different clinical stages.Wilcoxon rank-sum test,unpaired t-test and univariate linear regression analysis were used for data analysis.Results A total of 16 cases were collected.Alanine transaminase and aspartate transaminase was 59.25 U/L and 25.50 U/L,108 U/L and 45 U/L,respectively,after 6 months of onset and follow-up,and the differences were statistically significant.Moreover,total bile acids and albumin was 35μmol/L and 36.15μmol/L,and 32.45 g/L and 31 g/L,respectively,and the differences were not statistically significant.PA-HSOS pathological development process was divided into early,middle and late stages.In the early stage,the central lobular sinusoidal endothelium integrity was impaired and the entry of erythrocytes had interspersed thin reticular fibers and perisinusoidal space.In the middle stage(hemorrhagic zone),erythrocytes,reticular fibers and collagen fibers were lysed,densely collapsed and deposited.The cavity of the bloodstream was hyperemic and dilated,and the cavity was covered with sinus endothelial cells.The hepatic plate regenerated around the hemorrhagic zone and some of the hepatic sinuses were decompensated.In the late stage,deposited collagen in the hemorrhagic zone had formed a large fibrous scar,and most of the dilated cavity in the bloodstream was covered with vascular endothelium.The marginal zone hepatic cells were regenerated in two rows and gradually inserted into the fibrous septum.Different hepatic lobular lesions obtained from the same patients liver biopsy tissues were changed at different stages.Hepatic lobule injury proportion with severe internal bleeding in liver biopsy tissue had no relation with the prognosis of patients.Conclusion In the early stage of PA-HSOS,erythrocytes in the central zone of lobules enter the perisinusoidal space through the damaged sinus endothelium,which is manifested as hepatic plate hemorrhagic necrosis.In the middle and late stage,liver plate regeneration and vascular remodeling occurred,so most of the patients'clinical course was self-limited.Pathological staging and liver biopsy time have an apparent correlation,but the prognosis of patients cannot be judged based on the extent of hemorrhage and injury of biopsy samples.