長達 3 年的布勒韋單藥治療 HDV 相關肝硬化患者的安全性和有

StephenW

長達 3 年的布勒韋單藥治療 HDV 相關肝硬化患者的安全性和有效性


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慢性三角型肝炎 (CHD) 是一種罕見但嚴重的慢性病毒性肝炎，影響全球約 12-72 百萬患者。 [1]它由丁型肝炎病毒 (HDV) 維持，這是一種小型缺陷病毒，需要 HBV 的輔助功能才能複制和繁殖。 [2]在過去的 30 年中，唯一的治療方法是在標籤外使用 48 週療程的干擾素 (IFNα)。 [3]然而，這種抗病毒策略的特點是治療後反應有限，安全性較差。 [3], [4]

據我們所知，這是第一份評估 BLV 單藥治療長達三年的安全性、有效性和臨床反應的報告，這些患者的 HDV 相關代償性肝硬化患者禁用 Peg-IFN 治療。在這些難以治療的患者中長期使用 BLV 單一療法與陽性病毒學和臨床結果以及良好的安全性相關。所有患者都報告了對 BLV 治療的良好依從性（每天早上 2 次皮下注射），這由膽鹽水平的增加所證實，膽鹽水平是一種靶標參與的生物標誌物。

該研究最重要的發現之一是觀察到的陽性病毒學和生化反應，因為所有三名患者都達到並保持了檢測不到的 HDV-RNA，這是通過非常靈敏的測定進行測試的。由於至少三個原因，這些發現是前所未有的：第一，迄今為止沒有研究報告 BLV 治療超過 48 週的結果；第二，沒有數據證明減少劑量後病毒學反應仍然存在；第三，對於晚期代償性肝硬化等難治性患者，包括1例臨床顯著性門靜脈高壓症（CSPH）患者，長期使用本品治療的有效性尚未見報導。

另一個重要發現是我們在這些患者中觀察到的臨床反應。一名患有 CSPH 代償性肝硬化的患者，隨著 EV 的消退，肝功能檢查、AFP 和血小板水平以及門靜脈高壓特徵出現了臨床相關的改善。

StephenW

Safety and effectiveness of up to 3 years' bulevirtide monotherapy in patients with HDV-related cirrhosis


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Chronic hepatitis Delta (CHD) is a rare but severe form of chronic viral hepatitis that affects approximately 12-72 million patients worldwide.[1] It is sustained by the hepatitis D virus (HDV), a small defective virus that requires the helper function of HBV to replicate and propagate.[2] In the last 30 years, the only therapeutic approach has been the off-label use of a 48-week course of Interferon (IFNα).[3] However, this antiviral strategy is characterized by limited off-therapy responses and an unfavorable safety profile.[3],[4]

To our knowledge this is the first report assessing the safety, effectiveness and clinical response of BLV administered as monotherapy for up to three years in patients with HDV-related compensated cirrhosis in whom Peg-IFN therapy was contraindicated. The long-term administration of BLV monotherapy in these difficult to treat patients was associated with positive virological and clinical results coupled with a favorable safety profile. All patients reported excellent compliance to BLV therapy (2 subcutaneous injections every morning), as confirmed by the increase of bile salts levels, a biomarker of target engagement.

One of the most important findings of the study is the positive virological and biochemical response observed as all three patients achieved and maintained undetectable HDV-RNA, which was tested by a very sensitive assay. These findings are unprecedented for at least three reasons: first, no studies to date have reported the outcome of BLV treatment beyond week 48; second, no data exists to demonstrate that virological response was maintained upon dose reduction; third, the effectiveness of the administration of this drug for such a long-term in difficult to treat patients such as those with advanced compensated cirrhosis, including one case with clinical significant portal hypertension (CSPH), has never been reported so far.

Another important finding was the clinical response that we have observed in these patients. One patient who had compensated cirrhosis with CSPH, showed a clinically relevant improvement of liver function tests, AFP and platelet levels, as well as portal hypertension features, with the regression of EV.

StephenW

https://natap.org/2021/HBV/102521_01.htm