Persistent Control of Hepatitis B Virus and Hepatitis Delta Virus Infection Following REP 2139-Ca and Pegylated Interferon Therapy in Chronic Hepatitis B Virus/Hepatitis Delta Virus Coinfection.
Persistent Control of Hepatitis B Virus and Hepatitis Delta Virus Infection Following REP 2139-Ca and Pegylated Interferon Therapy in Chronic Hepatitis B Virus/Hepatitis Delta Virus Coinfection.
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DOI：
10.1002/hep4.1633
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发表时间：
2021-03
影响因子：
5.1
通讯作者：
Vaillant A
中科院分区：
文献类型：
--
作者：
Bazinet M;Pântea V;Cebotarescu V;Cojuhari L;Jimbei P;Anderson M;Gersch J;Holzmayer V;Elsner C;Krawczyk A;Kuhns MC;Cloherty G;Dittmer U;Vaillant A
REP 2139 - Ca和pegIFN对HBV/HDV共感染的有限治疗具有良好的长期安全性，并伴有HDV的高功能治愈率，肝功能正常化和HBV的额外功能治愈率。HBV功能性治愈伴随着cccDNA的失活/清除和整合HBV DNA的清除。核酸聚合物REP 2139抑制乙型肝炎病毒（HBV）亚病毒颗粒的组装/分泌。此前，在REP 301研究（NCT02233075）中，REP 2139‐Ca和聚乙二醇干扰素（pegIFN）在HBV/丁型肝炎病毒（HDV）共感染中实现了高的HDV RNA和乙型肝炎表面抗原（HBsAg）丢失/血清转化率。REP 301‐LTF研究（NCT02876419）在3.5年的随访期间检查了安全性和有效性。在目前的研究中，在REP 301研究中完成治疗的参与者被随访了3.5年。主要结局是安全性和耐受性，次要结局是HDV功能治愈（未检测到HDV RNA靶点[TND]，谷丙转氨酶[ALT]正常）、HBV病毒学控制（HBV DNA≤2000 IU/mL， ALT正常）、HBV功能治愈（HBV DNA TND; HBsAg <0.05 IU/mL， ALT正常）和HBsAg血清转化。补充分析包括高敏感性HBsAg （Abbott ARCHITECT HBsAg NEXT）、HBV前基因组RNA （pgRNA）、HBsAg/乙型肝炎表面抗体（anti - HBs）免疫复合物（HBsAg ic）和乙型肝炎核心相关抗原（HBcrAg）。2名参与者出现无症状的1‐2级ALT升高，并伴有病毒反弹；没有观察到其他安全性或耐受性问题。在治疗和随访期间，HBsAg降低至<0.05 IU/mL也<0.005 IU/mL。在REP 2139 - Ca单药治疗期间，11名参与者中有7名HBsAg ic下降，11名参与者中有10名在随访期间下降。11名参与者中有7人持续乙肝病毒功能性治愈；其中3人的HBV病毒学控制得以维持，4人的功能治愈（伴HBsAg血清转化）得以维持。HBV功能治愈伴HBV pgRNA、TND、HBcrAg <定量下限。结论：REP 2139‐Ca + pegIFN与长期安全性或耐受性问题无关。HDV功能治愈和HBV病毒学控制/功能治愈和HBsAg血清转化的建立持续超过3.5年，可能反映了肝脏中整合HBV DNA的去除。需要在更大规模的研究中进行进一步的调查。
Finite therapy of HBV/HDV co‐infection with REP 2139‐Ca and pegIFN has good long term safety and is accompanied by high rates of functional cure of HDV, normalization of liver function and additional functional cure of HBV. HBV functional cure is accompanied inactivation / clearance of cccDNA and clearance of integrated HBV DNA. The nucleic acid polymer REP 2139 inhibits assembly/secretion of hepatitis B virus (HBV) subviral particles. Previously, REP 2139‐Ca and pegylated interferon (pegIFN) in HBV/hepatitis delta virus (HDV) coinfection achieved high rates of HDV RNA and hepatitis B surface antigen (HBsAg) loss/seroconversion in the REP 301 study (NCT02233075). The REP 301‐LTF study (NCT02876419) examined safety and efficacy during 3.5 years of follow‐up. In the current study, participants completing therapy in the REP 301 study were followed for 3.5 years. Primary outcomes were safety and tolerability, and secondary outcomes were HDV functional cure (HDV RNA target not detected [TND], normal alanine aminotransferase [ALT]), HBV virologic control (HBV DNA ≤2,000 IU/mL, normal ALT), HBV functional cure (HBV DNA TND; HBsAg <0.05 IU/mL, normal ALT), and HBsAg seroconversion. Supplemental analysis included high‐sensitivity HBsAg (Abbott ARCHITECT HBsAg NEXT), HBV pregenomic RNA (pgRNA), HBsAg/hepatitis B surface antibody (anti‐HBs) immune complexes (HBsAg ICs), and hepatitis B core‐related antigen (HBcrAg). Asymptomatic grade 1‐2 ALT elevations occurred in 2 participants accompanying viral rebound; no other safety or tolerability issues were observed. During therapy and follow‐up, HBsAg reductions to <0.05 IU/mL were also <0.005 IU/mL. HBsAg ICs declined in 7 of 11 participants during REP 2139‐Ca monotherapy and in 10 of 11 participants during follow‐up. HDV functional cure persisted in 7 of 11 participants; HBV virologic control persisted in 3 and functional cure (with HBsAg seroconversion) persisted in 4 of these participants. Functional cure of HBV was accompanied by HBV pgRNA TND and HBcrAg <lower limit of quantitation. Conclusion: REP 2139‐Ca + pegIFN is not associated with long‐term safety or tolerability issues. The establishment of HDV functional cure and HBV virologic control/functional cure and HBsAg seroconversion are durable over 3.5 years and may reflect removal of integrated HBV DNA from the liver. Further investigation is warranted in larger studies.
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影响因子：
25.7
作者：
Petersen, Joerg;Thompson, Alexander J.;Levrero, Massimo
通讯作者：
Levrero, Massimo
DOI：
10.1002/cld.728
发表时间：
2018-04-01
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Terrault, Norah A;Lok, Anna S F;Wong, John B
通讯作者：
Wong, John B
DOI：
10.5501/wjv.v6.i2.26
发表时间：
2017-05-12
期刊：
World journal of virology
影响因子：
--
作者：
Alves, Carolina;Cheng, Hong;Cunha, Celso
通讯作者：
Cunha, Celso
影响因子：
8.8
作者：
Kuhns, Mary C.;Holzmayer, Vera;Cloherty, Gavin A.
通讯作者：
Cloherty, Gavin A.
影响因子：
35.7
作者：
Bazinet, Michel;Pantea, Victor;Vaillant, Andrew
通讯作者：
Vaillant, Andrew