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目的探讨肝移植病例中重型肝炎肝衰竭的病理组织学变化与其肝脏干细胞活化状态的关系。方法收集肝移植病例中重型肝炎肝衰竭33例,以相应供肝组织作为正常对照,以免疫组织化学 EnVision 法检测肝组织中 c-kit、Ki-67、HBsAg 及 HBcAg 表达情况,并选择10例 c-kit 明显阳性病例进行了甲苯胺蓝组织化学染色做为对比染色,分析肝衰竭病例肝脏病理组织学、病毒抗原表达、有无人工肝治疗史,c-kit 阳性肝脏干细胞活化数量。结果 33例中男性25例,女性8例,年龄分布为21～64岁。符合急性肝衰竭6例,其中2例与乙型肝炎病毒感染有关,3例为药物中毒所致,1例为急性妊娠脂肪肝;亚急性肝衰竭5例,均为乙型肝炎病毒感染所致;慢性急性发作性肝衰竭22例,均为乙型肝炎病毒感染所致。肝移植手术前有人工肝治疗史13例。肝脏活化的干细胞被 c-kit单克隆抗体所标记,但不能被甲苯胺蓝染料染色。正常供肝内无或偶见 c-kit 阳性细胞;急性肝衰竭组 c-kit 阳性细胞为3.50±2.66(0～8)个/mm~2;亚急性肝衰竭组为11.47±8,85(3～30)个/mm~2;慢性急性发作性重型肝炎组为15.50±10.95(5～45)个/mm~2,各组之间 c-kit 阳性细胞数差异有统计学意义。有无人工肝治疗史对 c-kit 阳性细胞计数无明显影响。供体肝脏组织 Ki-67染色阴性,而肝衰竭病例在汇管区或旁汇管区可以检测到数量不等的 Ki-67阳性细胞,但并不与 c-kit 阳性前体细胞呈平行关系。结论急性肝衰竭时肝细胞大片坏死但内源性干细胞活化不足是预后差的原因之一。而病程迁延较长的亚急性或慢性肝衰竭,肝脏干细胞活化水平逐渐升高,提示积极治疗肝衰竭使其设法渡过急性期,可以不同程度调动肝脏自身再生重建机制。
Objective To investigate the relationship between pathological changes of hepatic failure and liver stem cell activation in patients with liver transplantation. Methods Thirty-three cases of severe hepatic failure in liver transplantation were collected. The corresponding donor liver tissue was taken as normal control. The expression of c-kit, Ki-67, HBsAg and HBcAg in liver tissues were detected by immunohistochemical EnVision method. c-kit positive cases were treated with toluidine blue histochemical staining as contrast staining, analysis of liver failure liver histopathology, viral antigen expression, with or without artificial liver treatment history, c-kit positive liver stem cell activation number. Results 33 cases of male 25 cases, 8 females, the age distribution of 21 to 64 years old. In line with acute liver failure in 6 cases, of which 2 cases were associated with hepatitis B virus infection, 3 cases due to drug poisoning, 1 case of acute fatty liver of pregnancy; 5 cases of subacute hepatic failure, are due to hepatitis B virus infection ; 22 cases of chronic acute episode of liver failure, all due to hepatitis B virus infection. There were 13 cases of artificial liver treatment before liver transplantation. Liver-activated stem cells are labeled with c-kit monoclonal antibodies, but can not be stained with toluidine blue dye. No c- kit positive cells were found in normal donor liver. The numbers of c-kit positive cells in acute liver failure group were 3.50 ± 2.66 (0 ~ 8) / mm ~ 2, those in subacute hepatic failure group were 11.47 ± 8 and 85 The number of c-kit positive cells in each group was statistically significant (P <0.05). The number of c-kit positive cells in each group was statistically significant. No history of artificial liver treatment had no significant effect on c-kit positive cell counts. Ki-67 staining was negative in donor liver tissue, whereas Ki-67 positive cells ranging in number from portal area to portal area could be detected in liver failure patients, but not in parallel with c-kit positive precursor cells. Conclusions Acute liver failure with large hepatocellular necrosis but insufficient activation of endogenous stem cells is one of the reasons for poor prognosis. The longer duration of subacute or chronic liver failure, liver stem cell activation gradually increased, suggesting that active treatment of liver failure to make it through the acute phase, can be mobilized to varying degrees liver regeneration and reconstruction mechanisms.