A morphometric and immunohistochemical study to assess the benefit of a sustained virological response in hepatitis C virus patients with cirrhosis
A morphometric and immunohistochemical study to assess the benefit of a sustained virological response in hepatitis C virus patients with cirrhosis
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DOI：
10.1002/hep.25606
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发表时间：
2012-08-01
期刊：
影响因子：
13.5
通讯作者：
Bedossa, Pierre
中科院分区：
文献类型：
--
作者：
D'Ambrosio, Roberta;Aghemo, Alessio;Bedossa, Pierre
虽然环状纤维化是肝硬化的标志，但其他影响肝功能的微观变化，如窦状动脉毛细血管化或代谢分区丧失是常见的。持续的病毒学应答（SVR）可能阻止丙型肝炎病毒（HCV）感染患者的纤维化沉积，但其对其他肝硬化相关病变的影响尚不清楚。本研究的目的是评估SVR对肝硬化相关组织病理学特征的影响。对38例伴有SVR的肝硬化HCV患者治疗前后的配对肝活检进行了分析。使用METAVIR评分系统进行纤维化分期，使用形态测定法测量纤维化面积。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a-平滑肌肌动蛋白（aSMA）评估小管增殖、代谢分区、窦状毛细血管化和肝星状细胞活化。SVR结束61个月后，61%的患者肝硬化消退，89%的患者胶原蛋白含量下降。虽然门静脉周围和小叶坏死性炎症消失，但66%的门静脉炎症持续存在。导管增生减少92%。治疗前，GS和CYP2E1分别有71%和88%的代谢分区丧失，SVR后代谢分区恢复正常的比例分别为79%和73%。相反，通过CD34 （P = 0.41）和aSMA （P = 0.95）评估，治疗后未观察到窦状动脉毛细血管化的变化。最后，无论肝硬化是否持续存在，所有免疫组织化学评分均无差异。结论：肝硬化伴SVR的HCV患者常观察到肝硬化消退和纤维化减少。尽管小管增生消失，小叶分区恢复，门静脉炎症和窦状毛细血管化在病毒根除后可能不会消退。(肝脏病学2012)
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 a-smooth muscle actin (aSMA). 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 aSMA (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. (HEPATOLOGY 2012)