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一项形态计量学和免疫组织化学研究,评估丙型肝炎病毒肝硬化患者持续病毒学应答的获益。

A morphometric and immunohistochemical study to assess the benefit of a sustained virological response in hepatitis C virus patients with cirrhosis.

机构信息

A.M. and A. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.

出版信息

Hepatology. 2012 Aug;56(2):532-43. doi: 10.1002/hep.25606. Epub 2012 Jul 2.

Abstract

UNLABELLED

Although annular fibrosis is the hallmark of cirrhosis, other microscopic changes that affect liver function such as sinusoid capillarization or loss of metabolic zonation are common. A sustained virological response (SVR) may halt fibrosis deposition in hepatitis C virus (HCV)-infected patients, but its impact on the other cirrhosis-associated lesions is unknown. The aim of this study was to assess the impact of an SVR on cirrhosis-related histopathological features. Paired pre- and posttreatment liver biopsies from 38 HCV patients with cirrhosis with an SVR were analyzed. Fibrosis was staged using the METAVIR scoring system, and the area of fibrosis was measured using morphometry. Ductular proliferation, metabolic zonation, sinusoid capillarization, and hepatic stellate cell activation were assessed by anti-cytokeratin-7, anti-glutamine synthetase (GS), anti-cytochrome P4502E1 (CYP2E1), anti-CD34, and anti α-smooth muscle actin (αSMA). After 61 months from an SVR, cirrhosis regression was observed in 61%, and the collagen content decreased in 89%. Although periportal and lobular necroinflammation vanished, portal inflammation persisted in 66%. Ductular proliferation decreased in 92%. Before treatment, metabolic zonation was lost, as shown by GS and CYP2E1, in 71% and 88%, respectively, with normalization in 79% and 73%, after an SVR. Conversely, no changes in sinusoidal capillarization were observed after treatment, as assessed by CD34 (P = 0.41) and αSMA (P = 0.95). Finally, no differences in all the immunohistochemical scores emerged whether or not cirrhosis persisted.

CONCLUSION

Cirrhosis regression and decreased fibrosis are frequently observed among HCV patients with cirrhosis with an SVR. Despite ductular proliferation vanishing and lobular zonation restoration, portal inflammation and sinusoidal capillarization may not regress after viral eradication.

摘要

目的

评估持续病毒学应答(SVR)对与肝硬化相关的组织病理学特征的影响。

方法

分析 38 例丙型肝炎病毒(HCV)感染合并肝硬化且获得 SVR 的患者的配对治疗前后肝活检组织。采用 METAVIR 评分系统对纤维化进行分期,并采用形态计量学方法测量纤维化面积。通过抗细胞角蛋白 7、抗谷氨酰胺合成酶(GS)、抗细胞色素 P4502E1(CYP2E1)、抗 CD34 和抗 α-平滑肌肌动蛋白(αSMA)评估胆管增生、代谢分带、窦状隙毛细血管化和肝星状细胞激活。

结果

获得 SVR 后 61 个月,61%的患者观察到肝硬化逆转,胶原含量减少 89%。虽然门脉周围和小叶坏死性炎症消失,但 66%的患者仍存在门脉炎症。胆管增生减少 92%。治疗前,GS 和 CYP2E1 分别有 71%和 88%的患者出现代谢分带丢失,SVR 后分别有 79%和 73%的患者恢复正常。相反,CD34(P=0.41)和 αSMA(P=0.95)评估的窦状隙毛细血管化在治疗后无变化。最后,无论肝硬化是否持续,所有免疫组织化学评分均无差异。

结论

获得 SVR 的 HCV 感染合并肝硬化患者中,肝硬化逆转和纤维化减少较为常见。尽管胆管增生消失且小叶分带恢复,但病毒清除后门脉炎症和窦状隙毛细血管化可能不会消退。

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