13 Project Coordinator and her team 項目統籌人及團隊 Research Impact We will address the key issues of disease recurrence after liver transplantation through exploring the underlying mechanisms, identifying efficacious biomarkers, and developing new concept targeting immunotherapies as well as precise stem cell treatments through the integration of basic, translational and clinical research. The proposed study will not only generate scientific publications and patents, but also provide many opportunities to train future research talents. In addition to bibliometric output and education, we will also develop a unique computer modeling system essential for both disease prognoses and therapeutic guidance. Such novel digitalized platform and database will be durably important to form the infrastructure for precision medicine in transplantation. Discovery of druggable targets and exploration of new therapeutic strategies targeting disease recurrence after transplantation will open a new window for collaboration with local industries to enhance technology transfer. Development of novel immunotherapy will benefit the recipients’ long-term outcomes with both societal and economic impact. 研究影響 我們研究團隊針對肝移植後原發病復發的臨床問題和科學問 題，將進行一系列綜合性的基礎、轉化和臨床研究，冀在乙肝復 發的新型免疫治療、移植肝損傷研究的新理論、腫瘤復發機理 的全新闡釋和原發病復發的治療新策略等方面取得突破性進展 和新發現，這對於指導臨床決策和夯實肝移植後原發病復發的 理論基礎具有奠定性的重要作用。系列研究也將闡明肝移植術後 原發病復發的關鍵機制及調控途徑，不僅能豐富移植免疫與腫 瘤免疫新理論，亦為個體化預防原發病復發和改進免疫調控方 案提供理論依據和技術支撐，為香港地區乃至全國和全球的乙肝 與肝癌防治提供最優化解決方案。研究團隊也將和本地醫藥企 業進行協作研發，為進一步開展臨床試驗打下良好的基礎，開發 更具成本效益的新型免疫治療將創造更好的社會與經濟效益。 Abstract During the past two decades, we have successfully built an internationally renowned liver transplantation centre in Hong Kong. We pioneered in living donor liver transplantation (LDLT) using the right lobe liver graft in the world. This surgical innovation has successfully rescued almost 1500 patients with end-stage liver diseases and liver cancer in this sole transplantation center of Hong Kong. However, the prevalence of hepatitis B virus (HBV) infection, high incidence of liver cancer (Hepatocellular carcinoma-HCC) and the shortage of deceased organ donors in Hong Kong has burdened heavily on the healthcare systems. We face the grand challenges of recurrent diseases and liver graft injury after transplantation. Our TRS aims to improve the long-term outcomes of liver transplantation by tackling two major recurring diseases including cancer recurrence and HBV reactivation in Hong Kong through exploring underlying mechanisms, identifying efficacious biomarkers, and developing potential treatments by integrating basic, translational and clinical research. We hypothesize that novel approaches promoting liver tissue repair and regeneration will abrogate the limit of donor organ shortage. We have established a Biobank with comprehensive clinical database for more than 20 years with around 50000 tissue and liquid biopsies from almost 1400 adult recipients with 100% of patient follow-up. Based on this Biobank, we will establish a modeling system that integrates high-throughput sequencing data and biology/immunology parameters not only for predicting disease recurrence and prognoses, but also for therapeutic guidance. We will develop cost-effective immunotherapies as novel prophylaxis, especially for the pre-treatment of living donors, to benefit the recipients’ long-term outcomes with both societal and economic impact. The proposed multidisciplinary collaborative project will not only strengthen our local and regional excellence, but also enhance Hong Kong as an internationally leading centre of excellence in liver transplant. In addition to patient and economic benefits, this project will cement Hong Kong’s international stature in science, medicine and education. 項目簡介 在過去的二十多年，我們成功建立了蜚聲國際的香港大學瑪麗 醫院肝臟移植中心，在全球率先開展了成人右半肝活體肝移 植。這項外科技術的創新挽救了香港地區近一千五百位患有終 末期肝病和肝癌的病人。目前，香港地區乙型病毒性肝炎和肝 癌的高發病率給本地醫療保健系統帶來沉重的負擔，肝移植後 發生的移植肝損傷和原發病包括乙肝和肝癌的復發也是我們面 臨的巨大挑戰，這更使香港醫療保健系統百上加斤。我們的研 究專案旨在通過一系列基礎、臨床與轉化研究來揭示肝移植後 原發病復發的機制，尋找有效的生物標誌物，並開發新的治療 方案，以減少移植後乙肝和肝癌的復發，提高肝移植病人的長 期生存率。為解決腦死亡供體匱乏的問題，我們也致力於探索 促進邊緣性供肝組織修復和再生的新策略。我們的肝移植中心 已建立了逾二十年的生物樣本庫與病人資料庫，其中包括近一 千四百位肝移植病人的組織和血樣本五萬多個，病人的隨訪率 達到百分之百。基於這個完善的生物樣本庫與病人資料庫，我 們將整合高通量基因測序及生化和免疫資料，建立一個嶄新的 智能模型，不僅能用於腫瘤復發的預測，而且對治療策略的選 擇也有重要的指導意義。我們也將開發新型免疫治療以改善病 人預後，在擴大病人獲益的同時創造更好的社會與經濟效益。 此項多學科合作研究不僅能鞏固我們肝臟移植中心在亞太地區 的領導地位，而且可以進一步強化我們在國際移植界，特別是 活體肝移植領域的領先優勢，亦更有利於提升香港在科學、醫 療和教育的國際地位。
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