研究背景: 透過有效的抗病毒治療(antiviral therapy, AVT)抑制B型肝炎病毒(hepatitis B virus, HBV)複製已被多項研究證實可以消除絕大多數慢性B型肝炎(chronic hepatitis B, CHB)相關的壞死性炎症活動和肝纖維化的進展，儘管如此，部分CHB患者血清HBV-DNA仍維持在<2,000 IU/mL或可測得但低病毒量(全球建議的檢測下限20 IU/mL)狀態的低病毒血症(low-level viremia, LLV)患者，依舊暴露於發展為肝硬化或肝癌的風險。本研究旨在探討低病毒血症之慢性B型肝炎患者發生肝細胞癌(hepatocellular carcinoma, HCC)的危險因子與長期預後分析，並建立風險評分系統(risk scoring system)及預測模型。
研究方法: 本研究納入2008年1月1日至2020年12月31日間在三間醫療院所，即奇美醫學中心、柳營奇美醫院及佳里奇美醫院接受抗病毒治療超過12個月的慢性B型肝炎患者，進行回溯性世代研究，並將患者分為LLV組、維持病毒學反應(maintained virological response, MVR)組及HBV-DNA>2000組進行比較。使用Kaplan-Meier方法評估患者進展為ESLD與HCC的累積發生率(cumulative incidence rate, CIR)。實行Cox回歸分析(Cox regression analysis)確定最終的危險因子和風險因素，以構建風險評分系統與預測模型。
結果: 在這項研究中，確定了LLV患者發生 HCC 的風險的危險因子，評估了與 LLV 狀態的相關因素 ，包括男性、年齡、存在肝硬化、使用Baraclude 0.5mg或Telbivudine(600mg)抗病毒藥物、血小板(Platelet)、腎絲球過濾率 (eGFR)和天門冬胺酸轉胺酶(Aspartate Transaminase, AST)。丙胺酸轉胺酶(Alanine transaminase, ALT)和FIB-4 scores 則顯示出了邊緣的關聯。透過多變量Cox迴歸分析調整後發現與LLV患者發生HCC的重要關鍵因素，包括男性、年齡、存在肝硬化者和Platelet，在追蹤期間需要更密切的關注。透過多變量Cox迴歸分析確定的重要危險因子，為臨床上常規廣泛運用的實驗室參數，建立了一個準確性與便利性佳，分別針對LLV患者與所有HBV患者預測HCC發生風險的nomogram 。
結論: 這項回溯性世代研究，確定了LLV患者發生HCC風險與MVR患者相當，並建構了可有效監測LLV狀態的HCC風險預測模型。

Past research results show that patients with chronic hepatitis B patients (CHB) who maintain serum HBV-DNA<2,000 IU/mL of low-level viremia (LLV) are not at low risk of developing hepatocellular carcinoma (HCC). The aim of this study was to investigate the risk and risk factors of HCC in CHB with LLV. This retrospective cohort study includes patients with chronic hepatitis B who received antiviral therapy for more than 12 months at three medical institutions including Chi Mei Medical Center in southern Taiwan, from 2008 to 2020, and patients will be divided into LLV group, maintained virological response (MVR) group and HBV-DNA>2000 group to comparison. The cumulative incidence of progression to HCC has been assessed through the Kaplan-Meier method and Cox regression analysis is performed to determine the final risk and prognostic factors. During the follow-up period, the 3, 5, and 10-year cumulative HCC risks in the MVR group were 3.64%, 4.98%, and 10.54%, respectively; in the LLV group, they were 3.56%, 4.96%, and 9.51%, respectively (p-value: 0.970). Independent risk factors for HCC in LLV patients identified by multivariate Cox regression analysis were male, age, presence of cirrhosis, and platelets. This study determined Important critical factors in the development of HCC in LLV patients. The risk of HCC in patients with LLV status during follow-up was comparable to that in the MVR group.

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