Human liver regeneration following massive hepatic necrosis: Two distinct patterns
Human liver regeneration following massive hepatic necrosis: Two distinct patterns
复制标题
DOI：
10.1111/jgh.14721
复制
发表时间：
2020-01-01
影响因子：
4.1
通讯作者：
Paku, Sandor
中科院分区：
文献类型：
--
作者：
Dezso, Katalin;Nagy, Peter;Paku, Sandor
背景和目的大面积肝坏死是一种罕见的，但往往是致命的并发症，各种肝损伤。然而，一些患者可以通过自发性肝再生存活。已知存活的肝细胞和/或祖细胞可参与该过程，但肝脏恢复的机制尚不清楚。方法对13例急性肝功能衰竭患者的肝脏进行了检查。联合应用免疫组化、数字图像分析和连续切片的三维重建。结果可区分两种再生模式。在小叶中心坏死的肝脏中，存活的受损门静脉周围肝细胞开始增殖并排列成腺泡结构，并表达甲胎蛋白。如果损伤几乎消灭了所有的肝细胞，则大面积的实质损失被强烈的小管反应侵入。胆管远极细胞分化为肝细胞，并形成由门静脉分支组成的病灶。扩张灶常包含完整的门静脉三联体，分布在残存的中央静脉周围。它们的融合最终可能是试图重建肝小叶。结论人肝大面积坏死后再生可通过两种途径发生--甲胎蛋白阳性腺泡排列的肝细胞增殖或通过导管祖细胞，后者效率较低。对这些再生途径的进一步研究可能有助于确定完全再生可能性的生物标志物，因此具有治疗意义。
Background and Aim Massive hepatic necrosis is a rare but often fatal complication of various liver injuries. Nevertheless, some patients can survive by spontaneous hepatic regeneration. It is known that surviving hepatocytes and/or progenitor cells can participate in this process but the mechanism of hepatic recovery is vague. Methods We examined 13 explanted human livers removed for acute liver failure. Combined immunohistochemistry, digital image analysis, and three-dimensional reconstruction of serial sections were applied. Results Two patterns of regeneration could be distinguished. In livers with centrilobular necrosis, the surviving injured periportal hepatocytes started to proliferate and arrange into acinar structures and expressed alpha-fetoprotein. If the injury wiped out almost all hepatocytes, large areas of parenchymal loss were invaded by an intense ductular reaction. The cells at the distal pole of the ductules differentiated into hepatocytes and formed foci organized by the branches of the portal vein. The expanding foci often containing complete portal triads were arranged around surviving central veins. Their fusion eventually could be an attempt to re-establish the hepatic lobules. Conclusions Regeneration of human livers following massive hepatic necrosis can occur in two ways-either through proliferation of alpha-fetoprotein-positive acinary-arranged hepatocytes or through ductular progenitor cells, with the latter being less efficient. Further investigation of these regenerative pathways may help identify biomarkers for likelihood of complete regeneration and hence have therapeutic implications.