Stagnation of histopathological improvement is a predictor of hepatocellular carcinoma development after hepatitis C virus eradication.
Stagnation of histopathological improvement is a predictor of hepatocellular carcinoma development after hepatitis C virus eradication.
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DOI：
10.1371/journal.pone.0194163
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Kawada N
中科院分区：
文献类型：
--
作者：
Motoyama H;Tamori A;Kubo S;Uchida-Kobayashi S;Takemura S;Tanaka S;Ohfuji S;Teranishi Y;Kozuka R;Kawamura E;Hagihara A;Morikawa H;Enomoto M;Murakami Y;Kawada N
肝细胞癌（HCC）发生在一些通过抗HCV治疗对丙型肝炎病毒（HCV）感染实现持续病毒学应答（SVR）的患者中。为了研究HCV根除后HCC发展的发病机制，对SVR患者的组织病理学变化和临床标志物进行了评价。在接受干扰素（IFN）治疗的654例SVR患者中，入组了34例在开始IFN治疗前和达到SVR后接受肝活检的患者：11例HCC患者和23例非HCC患者（男性/女性，分别为9/2和8/15;年龄分别为58 ± 5和54 ± 11岁）。比较两组患者的临床及病理特点。还进行了细胞珠蛋白（CYGB）和α平滑肌肌动蛋白（α-SMA）的免疫组化。在基线时，在开始基于IFN的治疗之前，在男性性别、HBc抗体阳性、凝血酶原活性和组织学炎症分级方面，SVR-non-HCC和SVR-HCC组之间存在显著差异。使用新的犬山分类系统进行的组织学评估显示，在97 ± 72个月的观察期内，SVR-HCC组的炎症分级从2.1 ± 0.6改善至1.0 ± 0.6（p < 0.0001），而纤维化分期保持不变，从2.3 ± 0.9改善至2.0 ± 1.2（p = 0.2749）。SVR-非HCC组的分级和分期评分均显著改善。使用天狼星红染色评估的胶原沉积面积显示，在SVR-non-HCC组中从18.6 ± 7.6%显著降低至7.7 ± 4.6%，而在SVR-HCC组中没有变化。CYGB和α-SMA阳性肝星状细胞（HSC），指示HSC活化表型，保留在SVR-HCC组患者的肝脏纤维化组织中。纤维化消退停滞与SVR后HCC的高风险相关。HSC活化可能抑制SVR后纤维化的改善，并可能导致肝癌发生。
Hepatocellular carcinoma (HCC) develops in some patients who achieve sustained virological response (SVR) against hepatitis C virus (HCV) infection via anti-HCV therapy. To examine the pathogenesis of HCC development after HCV eradication, histopathological changes and clinical markers were evaluated in SVR patients. Of 654 SVR patients treated with interferon (IFN)-based therapies, 34 patients who had undergone liver biopsy before initiating IFN therapy and after SVR achievement were enrolled: 11 patients with HCC and 23 patients without HCC (male/female, 9/2 and 8/15, respectively: age, 58 ± 5 and 54 ± 11 years, respectively). We compared the clinical and histopathological factors between the two groups. Immunohistochemistry for Cytoglobin (CYGB) and α smooth muscle actin (α-SMA) was also performed. At baseline, prior to initiating the IFN-based therapy, there were significant differences between the SVR-non-HCC and SVR-HCC groups in the male gender, HBc antibody positivity, prothrombin activity, and histological inflammatory grade. Histopathological evaluation, using the new Inuyama classification system, revealed an improvement in the inflammatory grade, from 2.1 ± 0.6 to 1.0 ± 0.6 (p < 0.0001), whereas the fibrosis stage remained unchanged, from 2.3 ± 0.9 to 2.0 ± 1.2 (p = 0.2749), during the 97 ± 72-month observation period in the SVR-HCC group. Both the grade and stage scores were significantly improved in the SVR-non-HCC group. The area of collagen deposition, evaluated using Sirius red staining, showed a marked decrease, from 18.6 ± 7.6% to 7.7 ± 4.6%, in the SVR-non-HCC group, with no change in the SVR-HCC group. CYGB- and α-SMA-positive hepatic stellate cells (HSCs), indicative of the HSC activated phenotype, remained in the fibrotic tissue of livers among patients in the SVR-HCC group. Stagnation of fibrosis regression is associated with a high risk for HCC after SVR. HSC activation may inhibit improvement in fibrosis after SVR and potentially contribute to hepatocarcinogenesis.
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影响因子：
25.7
作者：
Conti, Fabio;Buonfiglioli, Federica;Brillanti, Stefano
通讯作者：
Brillanti, Stefano
影响因子：
13.5
作者：
George, Sarah L.;Bacon, Bruce R.;Brunt, Elizabeth M.;Mihindukulasuriya, Kusal L.;Hoffmann, Joyce;Di Bisceglie, Adrian M.
通讯作者：
Di Bisceglie, Adrian M.
影响因子：
25.7
作者：
Cucchetti, A;Vivarelli, M;Pinna, AD
通讯作者：
Pinna, AD
DOI：
10.4049/jimmunol.1500139
发表时间：
2015-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Li Y;Kim BG;Qian S;Letterio JJ;Fung JJ;Lu L;Lin F
通讯作者：
Lin F
影响因子：
6.2
作者：
Makiyama, A;Itoh, Y;Okanoue, T
通讯作者：
Okanoue, T