转化生长因子β1 (TGF β1)与慢性病毒性肝炎患者组织病理学表现的关系及预测意义

Bugdaci Mehmet Sait, Karaca Cetin, Koksal Ali Rıza, Boga Salih, Alkim Canan, Sokmen Mehmet
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Methods: Patients with Chronic Hepatitis B (CHB) and C (CHC), Non-Alcoholic Steatohepatitis (NASH), inactive HBsAg carriers, patients with cirrhosis and healthy control cases presenting to the Gastroenterology Clinic of Sisli Etfal Training and Research Hospital between 2009-2010 were included in the study. Laboratory tests, HCV RNA, HBV DNA, viral load, and viral markers (such as HBsAg, anti-HCV) were determined. Biopsies were performed on patients with hepatitis B and C, and non-alcoholic steatohepatitis (NASH). Histologic features were defined as Histologic Activity Index (HAI) and fibrosis stage (Knodell’s scoring). TGF β1 was evaluated by the ELISA method. 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摘要

背景:慢性病毒性肝炎(CVH)是肝细胞癌和肝硬化相关肝纤维化的最常见原因。肝活检是诊断肝纤维化的金标准。TGF β1是一种多效性细胞因子,在癌变和纤维化中起关键作用。关于TGF β1与组织病理学结果之间关系的研究结果存在争议。我们旨在探讨TGF β1与组织病理结果的关系。方法:选取2009-2010年在西西利训练与研究医院胃肠内科就诊的慢性乙型肝炎(CHB)和丙型肝炎(CHC)患者、非酒精性脂肪性肝炎(NASH)患者、非活性HBsAg携带者、肝硬化患者和健康对照患者。实验室检测、HCV RNA、HBV DNA、病毒载量和病毒标志物(如HBsAg、抗HCV)被确定。对乙肝、丙肝和非酒精性脂肪性肝炎(NASH)患者进行活组织检查。组织学特征定义为组织学活动指数(HAI)和纤维化分期(Knodell’s评分)。ELISA法检测TGF β1。结果:共纳入267例,其中非酒精性脂肪性肝炎44例[女性27例(57%)],HBsAg不活跃携带者38例[女性23例(60%)],慢性乙型肝炎48例[女性17例(35%)],慢性丙型肝炎27例[女性14例(60%)],失代偿性肝硬化15例[女性3例(20%)],健康对照94例。与健康对照组相比,其他亚组TGF β1水平均显著升高。TGF β1检测肝脏疾病的特异性为93.6%,敏感性为88.9% (AUC: 0.948, 95% CI: 0.916-0.981)。TGF β1与CHB、CHC患者的纤维化及组织学活动指数呈正相关。TGF β1与HBV DNA、HCV RNA呈负相关。TGF β1与CHB、CHC患者LDL、总胆固醇有显著相关性。结论:TGF β1与CHB、CHC患者HAI及纤维化均相关。TGF β1可能在CHC患者LDL水平升高和病毒载量降低的预后意义中发挥作用。
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The association with histopathological findings and predictive significance of transforming growth factor beta 1 (TGF β1) in patients with chronic viral hepatitis
Background: Chronic Viral Hepatitis (CVH) is the most common cause of hepatocellular cancer and cirrhosis related to liver fibrosis. The gold standard in the diagnosis of fibrosis is liver biopsy. TGF β1 is a pleiotropic cytokine that plays a pivotal role in carcinogenesis and fibrosis. The results of studies investigating the relationship between TGF β1 and histopathological findings are controversial. We aimed to investigate the relationship between TGF β1 and histopathological findings. Methods: Patients with Chronic Hepatitis B (CHB) and C (CHC), Non-Alcoholic Steatohepatitis (NASH), inactive HBsAg carriers, patients with cirrhosis and healthy control cases presenting to the Gastroenterology Clinic of Sisli Etfal Training and Research Hospital between 2009-2010 were included in the study. Laboratory tests, HCV RNA, HBV DNA, viral load, and viral markers (such as HBsAg, anti-HCV) were determined. Biopsies were performed on patients with hepatitis B and C, and non-alcoholic steatohepatitis (NASH). Histologic features were defined as Histologic Activity Index (HAI) and fibrosis stage (Knodell’s scoring). TGF β1 was evaluated by the ELISA method. Results: 267 cases including 44 non-alcoholic steatohepatitis cases [27 female (57%)], 38 inactive HBsAg carriers [23 female (60%)], 48 patients with chronic hepatitis B [17 female (35%)], 27 chronic hepatitis C [14 female (60%)], 15 decompensated cirrhosis [3 female (20%)] and 94 healthy control cases were included in the study. Compared with healthy controls, all other subgroups had significantly elevated TGF β1 levels. TGF β1 was found to have a specificity of 93.6% and a sensitivity of 88.9% (AUC: 0.948, 95% CI: 0.916-0.981) in determining liver diseases. TGF β1 had a positive correlation with fibrosis and histological activity index in patients with CHB and CHC. There was a negative correlation between TGF β1 and HBV DNA and HCV RNA. TGF β1 had a significant correlation with LDL and total cholesterol in cases with CHB and CHC. Conclusion: TGF β1 is correlated with both HAI and fibrosis in patients with CHB and CHC. TGF β1 might have a role in the prognostic significance of elevated LDL levels and low viral load in patients with CHC.
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