血漿TGF-β1濃度和B型肝炎相關之肝細胞癌危險性：前瞻型研究

Abstract

背景及目的：TGF-β1 為一多功能蛋白，參與免疫、發炎反應、肝纖維化、以及腫瘤生成。本研究目的為探討慢性B型肝炎病毒帶原者，其血漿TGF-β1濃度是否能預測肝細胞癌之危險性。 方法： 研究世代於1989至1992年間經由免費健檢收案進入研究，包括2903名B型肝炎表面抗原陽性之男性公務員接受血液檢體收集及訪視問卷。肝細胞癌病例的追蹤鑑定至2006年12月31日截止。透過病例世代研究設計，我們對164名肝細胞癌新發生病例及隨機抽樣獲得的1018名無癌症之個案分析血漿TGF-β1濃度。基線 TGF-β1的測量至肝細胞癌診斷期間由0.6年至16年（中位數：9.0年）。 結果：在調整其他危險因子下，血漿TGF-β1濃度的提高會顯著地增高罹患肝細胞癌之危險性。在肝細胞癌罹病風險預測模式(已包含：ALT、病毒相關因子、家族肝癌史、年齡、抽菸狀況、飲酒情形及身體質量指數)中加入 TGF-β1，亦會顯著地增加對肝細胞癌罹病風險的預測之準確度。 結論：我們的結果支持血漿TGF-β1有潛力作為肝細胞癌的一個生物標記。加入血漿TGF-β1於肝細胞癌危險性預測之演算模式，改善預測之準確性，然而，未來還需其他前瞻性研究的評估來證實。

Background & Aims: Transforming growth factor-β1 (TGF-β1) is a multifunction protein, which is involved in immunity, inflammation, fibrogenesis, and tumorigenesis. The aim of this study was to determine whether pre-diagnostic plasma levels of TGF-β1 could predict the risk of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV) carriers. Methods: Between 1989 and 1992, 2903 male hepatitis B surface antigen-positive government employees were recruited with blood collection and questionnaire interview during free physical examination. We identified HCC events occurring between study entry and December 31, 2006. Using a case-cohort study design, we analyzed the concentrations of TGF-β1 in plasma from 164 incident HCC cases and a random sample of 1018 examines free of cancer at baseline. Levels of TGF-β1 was measured in the baseline samples that were taken 0.6 to 16 years (median: 9.0 years) before the diagnosis of HCC. Results: Elevated plasma levels of TGF-β1 were significantly associated with an increased risk of HCC after adjustment for other HCC risk factors. The addition of TGF-β1 to known HCC risk factors (including alanine aminotransferase, various viral factors, family history of HCC, age, smoking, alcohol consumption and body mass index) improved the ability to predict future HCC events. Conclusions: Our findings support plasma TGF-β1 as a potential biomarker for HCC. The addition of plasma TGF-β1 to algorithms for prediction of HCC risk could improve accuracy; however, future prospective evaluation is warranted.