治療慢性乙型肝炎感染的最先進和新興抗病毒藥物

StephenW

治療慢性乙型肝炎感染的最先進和新興抗病毒藥物
瑪格麗塔 Papatheodoridi 1 , 喬治五世 Papatheodoridis 1
隸屬關係
聯繫

    1
    胃腸病學系，雅典國立和 Kapodistrian 大學醫學院，雅典總醫院“萊科”，雅典，希臘。

    PMID：36329612 DOI：10.1080/14656566.2022.2144219

抽象的

簡介：目前慢性乙型肝炎病毒（HBV）感染的治療方案無法實現功能性治愈[乙型肝炎表面抗原（HBsAg）丟失]；因此，正在研究新的方法。本綜述總結了在 Medline (2016-2022) 和歐洲和美國肝臟會議 (2019-2022) 中搜索後，新興抗 HBV 抗病毒藥物中最有希望的方法。

涵蓋的領域：抗病毒藥物的類別包括進入抑製劑 (bulevirtide)、衣殼組裝調節劑 (CAM)、翻譯抑製劑 [小干擾 RNA (siRNA)、反義寡核苷酸 (ASO)] 和 HBsAg 分泌抑製劑 [核酸聚合物 (NAP)]。 Bulevirtide 對乙型和丁型肝炎合併感染有良好的療效，但在 HBV 單一感染方面的數據有限。 CAM 可顯著降低血清 HBV DNA/RNA 水平，但對抗原水平的影響很小。 siRNA 和 ASO 主要降低 HBsAg 水平，但一小部分患者達到 HBsAg 血清學清除。 NAP 可降低血清 HBV DNA，尤其是 HBsAg 水平，提供可觀的 HBsAg 血清轉化率，但長期數據有限。開始評估不同類別代理的組合。

專家意見：需要繼續努力以解決關於有限持續時間的最佳聯合方案的許多未解決的問題，這些方案將是安全且耐受性良好的，可在相當大比例的慢性 HBV 患者中實現功能性治愈。

關鍵詞：反義寡核苷酸；衣殼組裝調節劑； cccDNA；進入抑製劑；功能性治愈；核酸聚合物；核苷；核苷酸；小干擾RNA。

StephenW

State-of-the-art and emerging antivirals for chronic hepatitis B infection
Margarita Papatheodoridi  1 , George V Papatheodoridis  1
Affiliations
Affiliation

    1
    Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece.

    PMID: 36329612 DOI: 10.1080/14656566.2022.2144219

Abstract

Introduction: Current treatment options for chronic hepatis B virus (HBV) infection cannot achieve functional cure [hepatitis B surface antigen (HBsAg) loss]; therefore, new approaches are under investigation. This review summarizes the most promising approaches in emerging antivirals against HBV, after search in Medline (2016-2022) and European and American liver meetings (2019-2022).

Areas covered: Classes of antivirals include entry inhibitors (bulevirtide), capsid assembly modulators (CAMs), translation inhibitors [small interfering RNAs (siRNAs), antisense oligonucleotides (ASOs)] and HBsAg secretion inhibitors [nucleic acid polymers (NAPs)]. Bulevirtide has good efficacy in hepatitis B and D coinfection, but there is limited data in HBV monoinfection. CAMs profoundly reduce serum HBV DNA/RNA levels, but have minimal effects on antigen levels. siRNAs and ASOs mostly reduce HBsAg levels, but small proportions of patients reach HBsAg seroclearance. NAPs reduce serum HBV DNA and especially HBsAg levels offering substantial HBsAg seroconversion rates, but having limited data over a long period. Combinations of agents of different classes are starting to be evaluated.

Expert opinion: Continued efforts are required in order to address many unanswered questions about the optimal combined regimens of finite duration which will be safe and well tolerated achieving functional cure in a substantial proportion of chronic HBV patients.

Keywords: antisense oligonucleotide; capsid assembly modulator; cccDNA; entry inhibitor; functional cure; nucleic acid polymer; nucleoside; nucleotide; small interfering RNA.